Microbiology Virus Revision (MVR)111. Pdf

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1. DNA VIRUSES
Cubic Icosahedral – Non-enveloped

Parvoviridae
Morphology: SS-DNA linear, replicate (host nucleus),
Parvovirus:
Animal parvovirus: Enteritis in animals  Canine parvovirus: Puppies  Feline panleukopenia virus: Kittens
Human Parvovirus B-19 (Erythrovirus B19): MT-respiratory, contact, blood. IP: 4-12 days
Species Pathogenesis Clinical manifestation Laboratory diag. Treatment & Prevention
Adenoassociated virus (AAV) Require adeno/herpes simplex virus for replication Defective virus
Densovirus Insect virus
Human Parvovirus B-19
(Erythrovirus B19)
Attack reticulocytes
Transient aplastic crisis (severe & acute anemia)
Chronic anemia
Reticulocytopenia, Viremia
Pregnancy (non-immune hydrophs fetalis, stillbirth)
Erythema Infectiosum (fifth disease)
Face: erythema (slapped cheek)
Arm/leg: maculopapular (lace-like)
Generalized lymphadenopathy, splenomegaly,
leukopenia, anemia, arthralgia
Difficult to culture

Serology: IgM, IgG
NO specific drug/ vaccine

HNIG (human Ig)

Papillomaviridae Morphology: DS-DNA circular, replicate (host nucleus)
Papilloma virus genes: L1, L2, E1, E2, E3, E4, E5, E6 (degrade p53), E7 (bind to RB protein), E8
HPV:- MT: sex, contact, autoinoculation, mother-baby (birth => laryngeal papilloma), SI (only human)
Species Pathogenesis Clinical manifestation Laboratory diag. Treatment & Prevention
APV (Animal papilloma virus)
HPV (Human papilloma virus) Infect cells in basal layer of
squamous epithelium => don’t enter
blood => no viremia => remain in
skin => Wart => 95% (no cancer), 5%
(cancer)
Plantar warts/ verrucae plantaris (1)- benign
Common Hand warts/ verrucae vulgaris (2)-
benign
Cancer (16, 18, 31, 33, 35, 39)
Genital/ venereal warts/ codylomata accuminata
(41,42)- benign
Electron micro.
Fluorescent Ab stain
PAP smear
PCR
Freezing (skin warts)
Podophyllin (antimitotic)
Salicylic acid(keratolytic)
Electro diathermy
Surgery. Quadrivalent vaccine:
(6, 11, 16, 16, 18)

Polyomaviridae
Classifications: BKV, JCV, Simian virus-40 (SV-40-monkey)
Target cells: JCV Brain-oligodendrocytes, BKV Kidney. JC & BK viruses maintain a latent infection-----reactivated from time to time
Modes of transmission: Inhalation respiratory droplets. Have 1
0
& transient viremia.
Immunocompetent => virus become latent in kidney
Immunocompromised => BK virus (viruria-presence of viral DNA in urine, hemorrhagic cystitis), JC virus (PML/progressive multifocal leukoencephalopathy)
Species Pathogenesis Clinical manifestation Laboratory diagnosis Treatment & Prevention
JC virus PML: slow, sub-acute degeneration of CNS =>
impaired memory & seizure => death
↑/normal lymphocytes in CSF, Foci of demyelination surrounded by giant astrocytes
containing intranuclear inclusion bodies. JCV particles in the nuclei of oligodendrocytes.
Culture: Difficult to grow. Serology
No specific treatment
BK virus associated with human prostate cancer Urine: inclusion bearing cells, EM. Culture: Difficult to grow. Serology No specific treatment
SV-40 Monkeys: Lymphocytic leukemia
Cubic Icosahedral – Enveloped


Herpesviridae
α-herpesvirinae: Herpes simplex virus type-1 (HHV-1), Herpes simplex virus type-2 (HHV-2), Varicella-Zoster virus (HHV-3)
β-herpesvirinae: Cytomegalovirus (CMV) (HHV-5), Human herpesvirus-6 (HHV-6), Human herpesvirus-7 (HHV-7)
γ-herpesvirinae: Epstein Barr virus (EBV) (HHV-4), Human herpes virus-8 (HHV-8) (Kaposi's sarcoma-associated herpes virus)
HHV-1(above the waist) & HHV-2 (below the waist)
Genomic organization (50-70% homology), but they differ in their biochemical, epidemiologic & clinical characteristics.
GD: Worldwide. SI: Humans. MT: HHV-1 (direct contact-saliva, infected secretions), HHV-2 (sex, congenital, perinatal). IP (3-5 days)
Site of latency: HSV-1: Trigeminal sensory nerve root ganglia, autonomic ganglia of superior cervical & vagus nerve. HSV-2: Sacral nerve dorsal root ganglia (S2-S3)
Latency => stress, fever, menstruation, pneumococcal/meningococcal infection, sunlight/ => Recurrent herpetic lesions (skin/mucus membranes) => Cold sore

2. HHV-1: Vesicular => Pustular => Ulcerative lesions. Gingivostomatitis (Herpes labialis-vesicular lesions border of lips), Herpetic whitlow (Painful vesicular lesions of
the finger/nails + lymphadenopathy. Commonly seen in dentists, hospital personnel, anesthetists). Keratoconjunctivitis (Corneal scarring, blindness),
Herpetic gladiatorum (in wrestlers => direct contact => head & neck region). Eczema herpeticum (commonly seen in children Severe eczema/burn/atopic
dermatitis & life threatening). Encephalitis (Temporal region of brain => focal neurological signs + cerebral edema). Aseptic meningitis.
HHV-2: Genital/anal/pharyngeal herpes (Painful vesicular-ulcerative lesions, herpetic erosions, Inguinal L.Ns enlargement, 1-10% aseptic meningitis).
Recurrent genital infection (Grouped vesicular lesions). Fetus and newborn (TORCH) complex (Congenital malformation/abortion, Vesicular ulcerative lesions,
Encephalitis, Chorioretinitis, microcephaly, Multiple organ involvement, MR: 50-60%).
Varicella-Zoster Virus (HHV-3)
Varicella (chicken pox): Primary infection: highly infectious. Herpes-zoster (shingles): Reactivation of Latent virus (dorsal root of sensory ganglia of spinal cord).
GD: Worldwide. Age: Children (2-6 years): epidemic, Adults: Sporadic. MT: Inhalation, direct contact, congenital. IP: 11-21 days. Target: Mucoepithelial cells.
Varicella (Chicken pox) (ጉድፍ): Fever, malaise, myalgia, Maculo-papular vesicular rash: pruritic/itching type: Centrifugal spread. Complications: pneumonia,
encephalitis, nephritis: MR: 20%.
Herpes Zoster (Shingles) (አልማዝ ባለጭራ): Common in adults. Vesicular-pustular ulcerative lesions. Skin (painful vesicular lesions over dermatome that are
innervated by a single ganglion (trunk, face, neck)-not diffuse). Eye (reactivation in the ophthalmic division of the sensory root trigeminal nerve (uveitis, keratitis,
iritis, conjunctivitis, ophthalmoplegia), Brain (Bell's Palsy: Reactivation in facial nerve). Complication of herpes zoster: Secondary bacterial infection, Secondary
viral infection: HSV, Post herpetic neuralgia –painful, Encephalitis.
Congenital Varicella syndrome: limbs (hypoplasia & skin scarring), damage to the lens, retina & brain & microphthalmia , death
EBV (HHV-4)
GD: Worldwide. MT: direct contact (saliva), blood transfusion, organ transplants. IP: 30-50 days. Targets: Epithelial cells (oro & nasopharynx) & B-lymphocytes.
Viral antigens: EBNA (nuclear antigen), Early antigen: non-structural proteins, VCA: viral capsid antigen, Viral envelope antigen.
90% of children are infected by EBV by the age of 6 in developing countries. Latency in B-lymphocytes
1. Primary infections: Infectious mononucleosis (IMN) (Glandular fever): flu-like symptoms, sore throat, cervical lymphadenopathy, splenomegaly, &
photophobia, white patches in tonsil, chronic EBV infection (pneumonia, hepatitis, hematological abnormalities).
2. Reactivation of latent virus: Burkitt's lymphoma (aggressive non-Hodgkin B-cell lymphoma): common in tropics (malaria-endemic regions).
Nasopharyngeal carcinoma: Adults (20-25 yrs.), SE. Asian countries-males. B-cell lymphoma: Immune suppressed. Hodgkin's lymphoma: EBV is present
in 40% of this disease. Oral hairy leukoplakia: on lateral surface of tongue, opportunistic infection of HIV-infected patients.
CMV (HHV-5)
GD: Worldwide. SI: Humans (saliva, urine, semen, cervical secretions, milk). MT: Fecal-oral, Inhalation, sex, blood transfusion, Congenital/perinatal/postnatal
transplanted organs. IP: 4-8 weeks. Prevalence: developing (90-100%), developed (40-80%) countries. Target (epithelial cells, WBC). Latent (in leukocytes).
Immunocompetent (asymptomatic/mild IMN-like disease), immunocompromised (Interstitial pneumonia, chorioretinitis, gastroenteritis, neurologic disorders).
Congenital infection (TORCH-complex): Intrauterine death, Abortion, Congenital abnormalities (CNS & RES). 20% (born healthy => abnormalities after 2 yrs.).
HHV-6 (HHV 6A & HHV 6B)
Epidemiology: Similar like CMV. SI: Healthy individuals shedding the virus-salvia. MT: Contact-salvia, intrauterine/perinatal. Age: Children.
Target cells: Lymphocytes, macrophages, & other cells. Latent: Macrophages
Exanthem subitum/Roseola infantum (sixth disease): Maculopapular rash + lymphadenopathy Common in infants and children. IMN like syndrome-adults.
Multiple sclerosis. Seizure. Chronic fatigue syndrome. Tumors. Cofactor in the progression of AIDS (transactivating HIV-1 promoter gene)
HHV-7
Similar clinical picture like HHV-6
HHV-8
Target cells: Endothelial cells & peripheral lymphocytes. Latency: Kaposi’s sarcoma tissue. Cause: Kaposi's sarcoma, Squamous cell carcinoma, B-cell lymphoma.
Species Pathogenesis Clinical manifestation Laboratory diagnosis Treatment & Prevention
HHV-1 & HHV-2 Mucoepithelial-vesicular-ulcerative lesions Specimen (vesicular fluids). Cell culture (fibroblasts). CPE
(Multinucleated giant cells, Ballooning degeneration of epithelial
cells + focal necrosis + intranuclear inclusion bodies). Serology.
Acylovir (not eliminate viral
shedding)
Foscarnet (Acyclovir resistant HSV)
HHV-3 (VZV) Varicella (chicken pox), Herpes Zoster (Shingles),
Congenital Varicella syndrome
Mainly clinical, EM (vesicular fluid), culture (human fibroblasts), CPE
(ballooning of cells), serology.
Acyclovir, Zoster immunoglobulin ,
Live attenuated varicella vaccine
EBV (HHV-4)

Primary & reactivation infections CBC, Leukocytosis + atypical lymphocyte (Downey cells) + indented
cell membrane, liver function test, serology, culture (difficult,
Supportive: >95% IMN is self-limited
Acyclovir

3. require human B-lymphocytes), Paul-Bunnel test(IgM agglutinates
sheep RBC-IMN diagnosis), histopathology (tumors)
Serology +ve: Biopsy of nasopharynx
is recommended due to cancer risk.
CMV (HHV-5)

In Immunocompetent & immunocompromised
Congenital infection (TORCH-complex)
Culture: Human embryo lung Fibroblast. CPE (owls eye appearance)
Large/swollen translucent cells + inclusion bodies-surrounded by
clear halo areas.
Ganciclovir, Cidovir
Hyper-immune anti CMV globulin
Live attenuated vaccine: experiment
Adenoviridae Aviadenoviruses: Birds. Mastadenoviruses: Mammals. First isolated from tissue cultures of human adenoidal tissue. Cause 5% of acute respiratory tract illness.
GD: Worldwide. SI: Environment. MT: Inhalation, Direct contact-instruments/swimming pools/ towels /ophthalmic solutions, Fecal-oral. IP: 2-14 days.
Have oncogenic potential in animals not humans. Latency: Tonsils (Adenoids), Peyer’s patches, Peripheral lymphocytes => recurrent => Acute phase of illness.
Antigenic structure: Capsid proteins: Hexones (cytotoxic), Pentones (serotyping), Fibers (Haemagglutinin), Early protein 3 (E3) (-interfere expression of MHC-I)
Species Pathogenesis Clinical manifestation Laboratory diag. Treatment & Prevention
Aviadenoviruses Birds Culture: Human embryonic kidney/epithelial cells. CPE: Rounding
& clustering of cells + refractile intranuclear inclusion bodies.
EM: Stool specimens. Serology
Ribavirin & cidofovir. Live attenuated vaccine
(enteric gelatin-coated capsule) (serotypes 4,
7, 21)Immunization of military recruits
Mastadenoviruses Mammals
Complex capsid-Enveloped

Poxviridae
Smallpox virus (Variola virus), Vaccinia virus & Molluscum contagiosum virus (human); Cowpox virus & Pseudo cowpox virus (cow); Monkeypox virus (monkey);
Elephant poxvirus (elephant); Orf virus (sheep/goat).
Smallpox virus (Variola virus)
Etiologic agent of smallpox (Variola):- Variola major virus: 20-50% MR. Variola minor virus: <1% MR.
GD: Worldwide (previously). MT: Inhalation, direct contact. IP: 4-5 days. SI: only Humans. B/c it is enveloped + brick-shaped => Virus survive in extracellular env’t for
weeks. Biological weapon. The largest DNA virus & the only DNA virus that replicate in cytoplasm. Don’t cause viremia.
Variola virus (smallpox virus) => 1
0
phase (multiplication in lymphoid tissue draining at the site of entry) => Transient viremia (RES) => 2
0
phase (multiplication in RES)
=> Viremia => Rash (all layers of skin).
Fever, chills, myalgia (1-5 days) => Skin rash (Face, extremities, less on the trunk) → Papular rash (1-4 days) →Vesicular rash (1-4 days) → Pustular rash (2-6 days)→
Crust formation → Pink scars (fades slowly). Hemorrhagic rash (severe cases of Variola major).
In smallpox, pocks are usually present on the palms of the hands. In chickenpox there may be few/no lesions on the palms of the hands.
Post vaccination complications: Superimposed bacterial infection, Generalized vaccinia (Children: eczema vaccinatum-MR: 30-40%), Contact vaccinia (After contact
with vaccinated person with live vaccinia vaccine), Encephalitis (MR: 40%), Progressive vaccinia (Vaccinia gangrenousum/necrosum)
Reasons for eradication of smallpox: No extra human reservoirs; Easily diagnosed; No asymptomatic/healthy carrier/subclinical infection; Vaccine easily prepared,
stable, & safe; Effective vaccine available; Prompt quarantine of patients and their contacts; One stable serotype; Infection confers long-term immunity.
Virus still kept: CDC, Atlanta, Georgia, USA & Russian center for Research on Virology and Biotechnology, Koltsovo, Novosibirsk region, Russia
Vaccinia virus
Etiologic agent of vaccinia. Wide host range. Antigenically related to smallpox virus. Used for smallpox vaccine. Used cloning vector for immunization against other
viruses (HBV- vaccine etc.): Recombinant vaccine.
Molluscum contagiosum virus
Etiologic agent of molluscum contagiosum. Common in children. Direct contact/Sex /sharing towels, shower rooms/swimming pools. IP: 2-8 weeks
Painless nodular skin (pear-like): face, arms, back, buttocks. Cheesy material; may be expressed at the center of lesions. It is self-limited, purely human pathogen.
Diagnosis: Mainly clinical, Large eosinophilic cytoplasmic inclusions "Molluscum bodies" –epithelial cells.
Cowpox virus
Etiologic agent of cowpox. Vesicular lesions confined to breast (teats & udders) of cows => direct contact lesions during milking => Vesicular lesions on milkmen's
hands. Natural reservoirs: rodents. Accidental hosts (cows & humans)
Pseudocow poxvirus
Etiologic agent of Milker’s nodules. Cutaneous disease in cattle. Human can be infected by directed contact with lesions
Orf virus (Goat & sheep pox viruses)
Sheep’s & goats (Pustular dermatitis + sore mouth), Human-sheep/goat handlers (nodular skin lesions-finger, hand/forearm)
Species Pathogenesis Laboratory diag. Treatment & Prevention
Smallpox virus
(Variola virus)
Specimen (vesicular fluids). Culture: embryonated hen’s egg (CAM-
chorioallantoic membrane)-Pock’s formation. Cytoplasmic inclusion
Vaccinia immunoglobulin. Edward Jenner: 1
st
vaccine-live attenuated- jet/
intradermal injection => post vaccination reaction

4. RNA VIRUSES
Cubic Icosahedral – Non-enveloped

Picornaviridae
Classifications: Enteroviruses: Polioviruses: 1-3; Coxsackie viruses-Group A: 1-24-Group B: 1-6; Echoviruses (enterocytopathic human orphanviruses: 1-34; Enteroviruses: 68-71.
Hepatovirus Hepatitis A virus (HAV) (Enterovirus-72). Rhinoviruses: >100 serotypes. Aphtovirus (Zoonotic).
I. Enteroviruses
Infect intestinal tract epithelial cells, lymphoid tissues (tonsils & Peyer’s patch) & shed into the feces. Resistant except, formaldehyde & hypochlorite. Major natural host (human).
Undergo antigenic mutation. Mucosal antibody (prevent initial establishment of infection) & serum antibody (prevents viremic spread to target tissue). Cell-mediated immunity (not
usually involved in protection).
GD: Worldwide. MT: Fecal-oral route, Inhalation (certain group A coxsackie), Contact. IP: 2-10 days. SD: Summer and fall/winter
Pathogenesis: initial organs => viremia/neural spread => target organs => inflammation => tissue damage.
1. Poliovirus (የልጅነት ልምሻ)
Target (CNS- anterior horn of brain stem & spinal cord-motor neuron). IP: 7-14 days. Age: all (more in children). SI: (only human). GD: (India & sub-Saharan Africa).
 In apparent infection (subclinical Infection) (90-95%): no symptoms.
 Abortive poliomyelitis (Abortive infection) (4-8%): minor illness. influenza-like symptoms. No CNS localization.
 Non-paralytic poliomyelitis (2%): Aseptic meningitis usually resolves without squeal within 2 - 10 days + signs of abortive poliomyelitis
 Paralytic Poliomyelitis (1-2%)
 Spinal poliomyelitis: spinal cord (85%): Asymmetrical flaccid paralysis of one or more limbs without sensory loss
 Bulbar poliomyelitis: Brain stem (15%) affect medulla oblongata => Paralysis of neck & respiratory muscles => MR: 75%
2. Coxsackie viruses
Herpangina (Vesicular pharyngitis): Group A: serotypes 2, 4, 5, 6, 8, & 10. Vesicular/papular/ulcerative lesions of mucous membrane (palate, pharynx, tonsils).
Summer minor illnesses: acute febrile illnesses, short duration (occur during summer/fall)
Pleurodynia (epidemic myalgia, Bornholm Disease, the Devil's Grippe): Group B: serotypes 1-5. Fever and sub-sternal chest pain (myositis of abdomen/chest)
Aseptic meningitis & mild paresis: Group B: all serotypes. Group A: 7, 9 & 24
Neonatal disease: Group B: all serotypes. Myocarditis/pericarditis + other organs (brain + liver)
Common cold: Group A: 10, 21, & 24, Group B: 3
Hand, Foot & Mouth Disease: Group A: 16, 5, 7, 9 & 10. Oropharyngeal ulcerations & vesicular lesion of the palms & soles. Common in children.
Myocardiopathy: virus-induced cross-reacting antibody. Group B: all serotypes. Group A: 4, 14. Echoviruses: 9 & 22. Common in children and adults. Self-limited, may be fatal
(arrhythmia and heart failure)/chronic dilated myocardiopathy.
Acute hemorrhagic conjunctivitis: Group A: 24
Diabetes Mellitus (Type 1): Group B: 4. Lesions in the pancreatic islets of Langerhans.
Rubelliform rash: Rash resembling rubella (maculopapular rash).
3. Echoviruses (enterocytopathic human orphan virus)
30 serotypes are known. Aseptic meningitis, encephalitis, febrile illnesses, rash, common cold, acute hemorrhagic conjunctivitis, paralysis, myocarditis.
4. Enteroviruses serotypes 68-71
Enteroviryse-68 (Bronchiolitis & pneumonia in children); Enterovirus-70 (Hemorrhagic conjunctivitis); Enterovirus-71 (Meningitis, encephalitis, paralysis resembling
poliomyelitis, hand, foot & mouth disease); Enterovirus-72 (Hepatitis A virus------hepatitis)
 Laboratory diagnosis: culture (Human embryonic kidney cells), serology (rarely used), PCR. Treatment: no specific treatment. Hepatitis-A (HAV vaccine)
 Polio vaccine: three serotypes (1-3). 3 doses (2, 4, 6 months): booster dose 1 & ½ years.
 Live attenuated vaccine-Oral polio vaccine (OPV)-Sabin-Vaccine-1957: Stimulate gut (local immunity) & systemic immunity. Live attenuated virus excreted in stool =>
disseminated in env’t => transmitted to non-immunized children by fecal-oral route => herd immunity” => eradication of wild poliovirus
 Advantage (effective, lifelong immunity, herd immunity, no need for repeated booster dose). Disadvantage (vaccine associated poliomyelitis, spread of vaccine to contacts
without their consent, not safe for immunodeficient person).
 Killed polio vaccine-Injection polio vaccine (IPV)-Salk-Vaccine 1954: Stimulate only systemic immunity that neutralizes the virus in the blood before reaching the CNS =>
protects against paralytic poliomyelitis.
Advantage (effective, safe for immunodeficient person, no risk of vaccine related disease). Disadvantage (lack of induction of secretory antibody, booster dose is required for lifelong
immunity, more painful injection, doesn’t prevent virus replication in the intestine => don’t protect against non-paralytic forms of infection).

5. II. Rhinoviruses
Acid labile, optimum T
0
-viral replication (33
0
c)-similar to T
0
of nasopharynx (target-URT)-binds to ICAM-1 glycoprotein. MT: inhalation, close contact. IP: 2-3 days
Common cold (30%): Mild fever, running nose-rhinitis, sneezing, sore throat, headache, chilly sensation, non-productive cough. All age groups (mainly older children & adults),
Epidemic peaks (in early fall or spring months), & 20 bacterial infections => acute otitis media, sinusitis, bronchitis or pneumonia.
Culture (in human embryonic kidney/lung cells at 33
0
c). No specific treatment & no vaccine.
Others viral causes of common cold: Coronavirus (10%); Adenovirus: type 5-10; Echovirus: types 4, 9, 11, 20, 25; RSV; Influenza virus; Parainfluenza viruses; Coxsackie virus A: type 21
III. Aphtovirus
Foot-&-Mouth disease in cattle, sheep, pig and goats (cloven footed animals). Vesiculo-ulcerative lesion-mucous membranes of the oropharynx, & skins of the foot. Highly
contagious/communicable: MR: 70%. Infected animals become poor producers of milk and meat. Animal to human transmission: contact infected animals/ingestion of their products.
Prevention: Vaccination of animals.
Helical-Enveloped
Orthomyxoviridae
Classification: Human Influenza virus (Three types A, B, C, based on ribonucleoproteins), Horse influenza virus, Swine influenza virus.
Antigenic structures: Envelope glycoproteins
I. Hemagglutinin (H): agglutinate red blood cells. To attach to N-acetylneuraminic (sialic) acid containing glycoprotein on human respiratory cell surfaces .Types (H1-H13)
II. Neuraminidase (N): acts on the hemagglutinin receptors by splitting off their terminal neuraminic (sialic) acid-facilitate entry & exit of virus to RT. Types (N1- N9)
Swine H1N1 flu virus NOT the same as human H1N1 virus-Antigenically very d/nt from human H1N1 viruses. Vaccines for human H1N1 can’t protect from swine H1N1.
III. Others: matrix proteins + ribonucleoproteins + polymerases
Antigenic drift: influenza viruses (A, B & C) => single /point mutation in the viral RNA (gradual change) => Minor antigenic changes in H/N antigen. Occur frequently.
Antigenic shift: Influenza A virus =>gene recombination/reassortment-b/n animal& human strains (sudden change) => Major antigenic changes in H/N ag. => new fatal strain
MT: direct (inhalation), indirect (contact to secretions), transmission (animal=> human, H => A, H=>H). SI: Influenza A virus (Human, animals & bird. Wild birds-natural hosts)
Influenza B & C viruses (Only humans). Age: any age group. SD: Common during midwinter months (seasonal flu). IP: 1-4 days. GD: Worldwide.
Pandemic alert phases
Phase 1 (animal to animal transmission) => Phase 2 (an animal influenza virus is capable of human infection) => Phase 3 (small outbreaks among close populations but not through
human to human contact) => Phase 4 (Human to human transmission) => Phase 5 (spread across two countries or more in one of the WHO regions/continents) => Phase 6 (spread
across two countries or more in one of the WHO regions plus spread to another WHO region).
 Pathogenesis: Influenza virus (entry through respiratory tract) =>Multiply in ciliated respiratory epithelial cells => Functional & structural abnormalities (inflammation) =>
Desquamation of both ciliated & mucus producing epithelial cells (not the basal layer of epithelium) => Interferes mechanical clearance mechanism of the respiratory tract
=> ↑susceptibly to 2
0
bacterial infection (S. aureus, Hib, S. pneumoniae). Viremia is rarely detected.
 Clinical features: Influenza syndrome (flu): Fever, myalgia, headache, shaking chills, non-productive cough, photophobia, dry tickling sore throat, running nose. Cough &
weakness may persist for 1-2 weeks after major symptoms subside. Croup (acute laryngotracheaobronchitis) in young children: barking cough, difficulty breathing, stridor
(sound during inspiration)
 Complications: CNS (encephalomyelitis & polyneuritis (autoimmune)), Myositis, Myocarditis, Children: Otitis media (12%), Sinusitis. Reye's syndrome: Infants and children
+ (adults); Severe fatty infiltration of the liver & cerebral edema (2-12 days) after the onset of infection; MR: 10-40%. 2
0
bacterial infection (superinfection) + sepsis.
1
0
viral pneumonia: direct progression of the virus to the lungs. Death
 Laboratory diagnosis: Virus culture: Embryonated hen's egg-amniotic cavity. Cell culture (monkey kidney cells). CPE (intranuclear inclusion bodies). Direct fluorescent
antibody stain (detect viral antigen from samples). Serology: Hemagglutination/Hemadsorption inhibition test. Molecular methods: detection of viral RNA (to differentiate
type A/B/C influenza viruses).
 Treatment
Seasonal flu (human): Supportive. Amantadine/rimantadine (↓viral load). Salicylates are avoided in children/young adults b/c of risk of developing Reye’s syndrome
H1N1 (swine flu): Supportive therapy. Resistant to Amantadine & Rimantadine. Neuraminidase inhibitors recommended (treatment & prevention of Influenza A & B)
Oral: Oseltamivir (Tamiflu). Inhaled: Zanamivir (Relenza). Antibiotics; Respiratory support.

6.  Prevention
Vaccine should be given before flu season. Antiviral chemoprophylaxis for close contacts.
Seasonal human flu: Formalin inactivated vaccine prepared from egg-grown virus (whole cell killed vaccine) vs. Purified subunit vaccine prepared from H & N antigens.
Available for Influenza A (H3N2 and H1N1 strains) & influenza B. Maximal protection (70-85%) for one year. Vaccination of individuals at high risk, especially those over 65
years of age & those with chronic cardiopulmonary disease, is recommended. Risk of developing Guillain-Barre syndrome after Formalin inactivated vaccine (1:100,000)
Swine flu: no vaccine available. Vaccine for human seasonal influenza doesn’t protect against H1N1 swine flu viruses due to antigenic differences, but may provide partial
protection against swine H3N2 virus
Paramyxoviridae Classifications: Paramyxovirus (HN, F) – Para influenza virus (1-4) & Mumps virus. Morbillivirus (H, F) - Measles/Rubeola virus. Pneumovirus (G, F) - RSV
(respiratory syncytial virus), Human metapneumovirus.
Antigens: H (hemagglutinin) & N (neuraminidase) – attachment to host cell. F (fusion protein) – fusion, penetration, hemolysis. G (G protein) - attachment to host
cell.
Fusion results in giant cell formation (syncytia). Antibody to F prevents spread of virus from cell to cell.
I. Parainfluenza viruses (HN & F)
Epidemiology and pathogenesis: Similar to influenza virus + no viremia. Host range limited to humans
Clinical features: Common cold, pharyngitis, laryngotracheobronchitis (croup), bronchiolitis, pneumonia & otitis media
Parainfluenza virus-1: Acute croup in infants & young children. Inspiratory stridor (‘crowing’), dry cough & hoarseness of voice due to swelling of the mucous
membrane + accumulation of mucus leads to air way obstruction. Mild URTI (tracheobronchitis and pharyngitis) in all age groups
Parainfluenza virus-2: Croup in children with mild URTI. LRTI (Occasionally).
Parainfluenza virus-3: Severe LRTI (bronchitis & pneumonia) in infants & young children
Parainfluenza virus-4: Least common of the groups & generally associated with mild URTI.
Treatment & control: no specific therapy or vaccine. In severe cases, the infants should be admitted to hospital & nursed in plastic tents supplied with cool,
moistened oxygen (croupette), kept for a day or two until their respiration becomes unlabored. Severe respiratory obstruction may require endotracheal
intubation followed by a tracheostomy.
II. Mumps Virus (HN) (ጆሮ ደግፍ)
Only one antigenic/serotype type is known. Cause mumps: acute contagious diseases - non-suppurative enlargement of salivary glands (mainly parotid glands).
GD: Worldwide. SI: only humans. Age: 5-15 years. MT: Inhalation, direct contact - saliva/urine. Highest infectivity 7 days before & after 9 days after onset of illness
(virus shed in the saliva). Person-person transmission common-large droplets. IP: 16-18 days.
 Pathogenesis: virus replicate after entry into the respiratory tract => Viremia/lymphatic spread => Dissemination to target tissues (salivary glands & CNS) =>
Secondary viremia then spread to other organs + kidney)-Viruria & renal impairment common => Inflammation & necrosis with predominately mononuclear cell
infiltration => Virus spreads throughout the body to pancreases, testes, ovary, & thyroid glands.
 Clinical features: 1/3 infected patients (in apparent/sub-clinical infection (but infectious)). Fever + swelling + tenderness of salivary glands, mainly parotid
glands (unilateral or bilateral) & persists for 7-10 days
 Other clinical syndromes: Aseptic meningitis. Encephalitis: MR-1-2%. Pancreatitis (Juvenile diabetes mellitus). Orchitis (Testes). Oophoritis (Ovary). Thyroiditis.
Nephritis. Arthritis. Sensorineural hearing loss (direct damage to the cochlea). Abortion (hormonal imbalances caused by virus infection).
 Laboratory diagnosis: Specimen (Saliva, CSF, urine). Virus culture: monkey kidney cells: CPE: syncytial with giant cells + rounding of cells. Embryonated hen's
egg: Allantoic cavity. DFA (Viral antigen detection in pharyngeal cells or urine sediment). Serology: EIA (IgM and IgG)
 Treatment & Prevention: no specific therapy.
Live attenuate mumps vaccine: Recommended for infants after the first year of life (protective 10 years): two doses separated by four weeks. Adults (men).
Available in monovalent form (mumps only) or in combination with rubella (MR) or measles & rubella (MMR) live attenuated vaccines.
III. Respiratory Syncytial Virus (RSV) (G & F)
Its name derived from its ability to produce cell fusion (syncytium formation). It possesses no Hemagglutinin (H) or Neuraminidase (N). Two antigenic subgroups
(A & B) are known to exist. Most important etiologic agent in respiratory diseases in infants (bronchiolitis & pneumonia).
GD: Worldwide. Age: Infants (< 1 years) & children-Outbreaks common in all families with children. MT: Inhalation, direct contact, nosocomial. IP: 1-4 days
 Pathogenesis: Infection is confined to respiratory epithelium - middle & lower airways (No viremia at all) => multiply---inflammation of RT-bronchi, bronchioles
& alveoli => necrosis of epithelial cells, interstitial mononuclear cell inflammatory infiltrates => plugging of smaller airways with mucus, necrotic cells & fibrin =>
multinucleated syncytial cells with intracytoplasmic inclusions are seen in the affected tracheobronchial epithelium (CPE).

7.  Clinical features:
 Infants: bronchiolitis (100% viral etiology), pneumonia, hypoxemia, hypercapnia (↑Co2). CXR (Interstitial infiltration, hyperexpansion + collapse of lung).
MR: 0.5-1% (due to cor Pulmonale & bacteria superinfection). 1/3 of children develop otitis media.
 Children & adults: mild illness (common cold & croup). Re-infection is common.
 Hospital staff & parents: common cold + fever + pharyngitis.
 Laboratory diagnosis: Virus culture: Human hetroploid cell lines-HeLa & HEp-2- tumor cells. Immunofluorescent (RSV infected cells- bright/apple green color).
 Prevention & treatment: no vaccine. Supportive. Ribavirin-effective. Close supervision for complications. RSV hyperimmune globulin: premature infants
IV. Measles (Rubeola) Virus (H & F) (ኩፍኝ)
Etiologic agent of measles (rubeola): acute highly infectious disease - maculopapular rash + fever + respiratory symptoms. Human pathogen & only one serotype.
Major cause of infant death (1-1.5 million deaths / year) in malnourished children. 30-40 million cases per year in unvaccinated populations.
SI: Humans. MT: Inhalation of respiratory droplets Outbreaks-common. Age: Children. IP: 7-18 days
 Pathogenesis: virus replicate after entry into the respiratory tract => further multiplication in regional lymphoid tissues (LN, tonsils/appendix) => 1
0
viremia =>
Lymphoid tissues, bone marrow, abdominal viscera (RES) => 2
0
viremia => Epithelial cells of skin, respiratory tract & conjunctiva (multiply) => Inflammation &
necrosis + vasculitis + multinucleated giant cells + intracytoplasmic/intranuclear inclusions (CPE).
 Clinical features: no asymptomatic carriers. After infection, there is lifelong immunity. Typical Measles is a 7 to 11 days illness.
A. Prodromal phase (2-4 days): Fever, cough, coryza (running nose), conjunctivitis (2-4 days). Koplik’s spots (1-2 days) (pin point bluish white spots surrounded
by erythema (grains-of-salt) over buccal mucosa opposite to molar teeth & persists for. Kolpik’s spots (giant cells + viral antigens + viral nucleocapsids)
B. Eruptive phase (5-7 days): Typical measles rash (maculopapular) (head => trunk & extremities-centrifugal spread) - due to cell-mediated immune response.
Cervical lymphadenopathy. MR: 15-25% in developing countries.
 Complications: Bacterial superinfection (5-15% cases): β-hemolytic Streptococci. Encephalitis (autoimmune) – MR (15%). Giant cell pneumonia.
Subacute Sclerosing Panencephalitis (SSPE): Slowly progressive fatal degeneration of the brain. 1:300,000 & 7:1 million cases. Occurs 1 to 10 years after
measles infections .Due to persistence of measles virus (defective) after acute measles infection. Insidious onset of personality change, poor school performance,
progressive intellectual deteriorations, development of myoclonic jerks (periodic muscle spasms), motor dysfunctions (spasticity, tremors, loss of coordination and
ocular abnormalities (cortical blindness). Mostly affect eye & CNS. Don’t have accepted effective therapy. Atypical measles: common in young adults who received
killed measles vaccine as children and then exposed to wild (natural) type of measles virus. High fever + abdominal pain + unusual rash (mainly over extremities &
spreads centripetally) + no Koplik’s spots + may confuse with Rocky Mountain Spotted fever (RMSF).
 Laboratory diagnosis: Virus culture only required in atypical cases. Viral antigen detection-pharyngeal cells/urinary sediment
 Treatment: no specific therapy. Ribavirin (severe measles). Supportive. Close observation for development of complications.
 Vaccine: Live attenuated measles vaccine - highly immunogenic (contain both F & H glycoproteins). Combined with mumps & rubella vaccines (MMR vaccine).
Effective, safe & long-lasting. Contradicted during pregnancy & immunocompromised host.
 Killed formalin inactivated measles vaccine, no longer available: don't produce protective immunity (selective inactivation F-glycoprotein)

Rubella Virus
Cubic/icosahedral capsid – Enveloped

Only one serotype & no extra-human reservoirs. Contagious (measles > rubella > mumps). Etiologic agent of rubella (German measles or 3 day measles). Contagious
from 7 days before & 7 days after the onset of rash. Infection during pregnancy (1
st
trimester) => serious abnormalities of the fetus-Congenital Rubella Syndrome.
GD: Worldwide. SD: Common in winter & spring. Age: Woman-childbearing age-during pregnancy. MT: Inhalation, Congenital. IP: 14-21 days.
Primary infection: Congenital malformation, Fetal death, Spontaneous abortion, IUGR, Virus shedding continues after birth (12-18 months).
Clinical features:
1. Postnatal Rubella: 30-60% clinically apparent disease. Mild febrile illness + mild sore throat, coryza, cough => Lymphadenopathy (posterior cervical & post-auricular)
=> Maculopapular rash (over the head, neck, & trunk) => Arthralgia or overt arthritis (joints of finger, wrists, elbows, knees and ankles)-common in women.
Complication: Progressive Rubella Panencephalitis (PRP). Rare. Results in mental & motor deterioration. Occurs at 8 to 19 years of age.
2. Congenital Rubella Syndrome (CRS) (TORCH-complex):
 Permanent defects: Cardiac defects (PDA, pulmonary & aortic stenosis, pulmonary valvular stenosis, VSD/ASD). Eye defects (total or partial blindness) -
Cataract, chorioretinitis, glaucoma. CNS defects (microcephaly, psychomotor retardation, encephalitis). Developmental defects (Sensorineural deafness,
mental retardation, insulin-dependent diabetes). Developmental defects may take months before they become apparent but persists permanently.
 Transient defects: IUGR, thrombocytopenic purpura, hepatosplenomegaly and hemolytic anemia. Present during the first few weeks of life & are not
associated with permanent sequelae.
 10 -20% of babies with CRS die within 1 year

8.  Laboratory diagnosis: Virus culture (rarely used for routine diagnosis). Serology- commonly used -IgG (confirmation of immunity), IgM: recent infection +
congenital infection
 Treatment: Mild, self-limited illness, no specific antiviral therapy. Supportive. Termination of pregnancy: Virus detected in the first 3-4 months of pregnancy.
 Prevention: Live attenuated rubella vaccine given SC. Confers immunity -95% (at least for 10-16 years). Non-pregnant women vaccinees should avoid conception
for at least 3 months after receiving vaccine. Vaccine contraindicated (Immunocompromised patients, pregnancy).

Zika virus
(ZIKV)
Vector: Aedes Mosquitoes (Arbovirus). Isolation: Zika Forest of Uganda-1947 in monkeys. MT: Mosquito bite; Human to human: Sex, congenital, perinatal, blood.
Clinical features : Zika Fever (Zika Virus Disease-ZVD))
Asymptomatic. Symptomatic: AFI: Fever, red eyes, joint pain, myalgia, headache, maculopapular rash, Guillain–Barré syndrome (GBS). Infection during pregnancy causes
microcephaly.
Diagnosis: Blood, urine, or saliva for the presence of Zika virus RNA when the person is sick
Treatment: Supportive. Prevention: Safe Sex, Insect repellent, Mosquitoes net, Restriction of travel, Postponing pregnancy, No effective vaccine (under clinical trial).

Rhabidoviridae

Rhabidoviridae
(Rabies Virus)
Sensitive to UV-radiation, sunlight, heat, lipid solvents. Wide host range of infection (warm blooded animals). Rabies (Zoonotic disease).
Gene product: Nucleoprotein (N), Polymerase phosphoprotein (P), Matrix (M), Glycoprotein (G), Large protein (L)
Epidemiology
SI: Urban form (Unimmunized dogs and cats). Sylvatic form (Foxes, wolves, jackals, mongooses, bats, raccoons, skunks)
GD: World wide-highest attack rate in South East Asia, India, N. Africa, the Philippines
MT: Bite of rabid animal/s, Contamination of scratch wounds, Animal-animal: Common, Animal-human: Common. Human-human: very rare (infected transplanted
cornea). Blind ended hosts (humans & cattle). IP: depends on dose of virus, site & size of the bite wound
Pathogenesis: site of bite (muscle/connective tissue) => NMJ (sensory nerves) => gray matter (CNS) => Salivary glands, kidneys, cornea, adrenal medulla, lungs
Neuropathology: hyperemia, nerve cell destruction, demyelination, negri body (eosinophilic cytoplasmic inclusion bodies-71% of cases)
Pathogenesis Clinical manifestation Laboratory diagnosis Treatment and Prevention
1. Animals
IP: 3-10 days
Prodromal phase:
Fever, malaise, anorexia,
behavioral change of animal-
irritable
Excitement phase:
Hyper excitability, Increased
salivation, Increased lacrimation
Paralytic phase:
whole body paralysis-coma-
death
2. Humans
IP: 2-16 wks (2-3 wks)
• Prodromal phase
• Sensory phase:
abnormal sensation at
the site/around the bite
• Excitement phase
• Paralytic phase

1. Demonstration of Negri body
2. Immunofluorescent technique: Rapid
viral antigen detection
3. Culture, serology, molecular methods
4.Animal inoculation (infant mice) of
saliva/ infected tissue (salivary gland and
brain) intracerebrally:- Observe paralysis
and death & Brain examination:
IF/Histopathology
DDx:
Tetanus, poliomyelitis, Guillain-Barre
(GBS), viral hepatitis, drug poisoning
I. Post-exposure prophylaxis
Wound treatment
Passive immunization: Human rabies hyper-Ig (HRIG), Equine rabies Ig (ERIG)
Active immunization
• Human diploid cell vaccine: HDCV-killed vaccine IM. 5-doses: days 1, 3, 7, 14
& 28
 Duck embryo vaccine: DEV-killed vaccine-SC
23 doses: daily for 21 days and booster dose at the days 31 and 41
 Nerve tissue vaccine (Mouse brain with inactivated rabies virus).
Complications -demyelinating allergic encephalitis. MR 3.13%
II: Pre-exposure prophylaxis
High-risk groups: HDCV-3 doses – IM. DEV -3/4 dose-SC
VIRAL AGENTS OF GASTROENTERITIS (ENTERIC VIRUSES)

Reoviridae
(Rotavirus)
Classifications: Human rotaviruses. Animal rotaviruses (kittens, puppies, calves, foals and piglets).
Posses’ double capsid (outer capsid, inner capsid) with characteristics of "wheel with radiating spikes" like structure. Account for 40-60% of cases of acute
gastroenteritis (diarrhea) in infants and children younger than two years of age and account for around half a million deaths in infants in developing
countries per year.
MT: Fecal oral route. IP: 1-3 days. SI: Infected persons Age: Children (< 2 years). SD: Winter (Outbreaks common)-Year round in the tropics. MR: 600,000-
850,000 deaths per year (20% of diarrhea-related deaths under age 5 years and 40% of severe diarrhea cases). Pathogenesis: duodenum & proximal
jejunum => Inflammation & destruction villous epithelial cells => ↓absorptive surface => ↓production of brush border enzymes (disaccharidases) =>
Malabsorption of fats and sugars + fluids and electrolytes loss => Diarrhea => 3-8 wks.(restore normal histological & functional integrity).

9. Pathogenesis Clinical manifestation Laboratory diagnosis Treatment and Prevention
Vomiting (1-3 days), watery diarrhea (5-8 days) (no
blood or leukocytes in stools) + low grade fever
Dehydration (mild to severe) • Electron microscopic examination
Latex agglutination:
 Supportive, Personal hygiene, Live attenuated oral
vaccine. Breast feeding (IgA)
Calcivirdae (Caliciviruses)

Norovirus (SRSV)(Norwalk-like viruses)

Sapovirus (Sapporo-like virus)
Epidemiology
First isolated in 1968, Norwalk, Ohio, USA
MT: Fecal-oral route. IP: 10-51 hrs.
Pathogenesis Clinical manifestation Laboratory diagnosis Treatment and Prevention
Similar to rotaviruses Gastroenteritis “stomach flu” in older children and adults

Others viral Agents of diarrhea
Adenovirus: Serotypes 40 and 41
Astrovirus: Small SS-RNA, non-enveloped virus 27-32nm in size and star shaped
Coronavirus, Reovirus , Small Round Viruses (SRV), Parvoviruses, Enteroviruses
CMV & HIV (in immunocompromised patients)

Coronaviridiae

Coronaviruses

Epidemiology
45 species. 4 genera: infect mammals/humans (α-CoV, β-CoV) & infect birds (γ-CoV, δ-CoV)
 Human Coronavirus
I. Common Cold-URTI: HCoV-229E- α-CoV, HCoV-OC43- β-CoV, (HCoV-HKU1)-β-CoV, (HCoV-NL63)-α-CoV
II. Severe Acute Respiratory Syndrome: Pneumonia-LRTI: (SARS)-COV-1- β-CoV, (SARS)-COV-2(COVID19)- β-CoV, (MERS)-COV- β-CoV
 Animal coronaviruses: Gastroenteritis/diarrhea (pigs and cows), Hepatitis/ encephalomyelitis (murine/mice), Bronchitis (birds)
SARS-CoV & MERS-CoV were transmitted to humans from bats by civet cats and dromedary camels, respectively
Antigenic structures
 Envelope glycoproteins
S (Spike glycoprotein): receptor binding, cell fusion, entry, major antigen (Angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN), and dipeptidyl
peptidase). Resemble a crown.
M (Membrane glycoprotein): transmembrane - budding & envelope formation. Define the virion morphology.
HE (Haemagglutinin-esterase): Destroying sialate O-acetylesterase activity for efficient virus infection and spread.
N (Nucleocapsid protein)
COVID19 (SARS-COV-2)
Epidemiology: Origin (Wuhan, China), IP (14 days)
Clinical Features: cough, fever/chills, shortness of breath, muscle/body aches, sore throat, new loss of taste/smell, diarrhea, headache, new fatigue,
nausea/vomiting, congestion/runny nose. Rare (severe respiratory problems, kidney failure or death)
The virus is no longer detectable on plastic after 72 hours and on stainless steel or cardboard after about 48 hours.
Three types of corona vaccine
1. Protein based: spike protein is purified & injected => immune system produce antibody (ISPAb)
2. Viral vector: spike protein gene is purified => Adenoviral vector is injected => body produce spike protein => ISPAb
3. mRNA: mRNA that code for spike protein is purified & injected => body produces spike protein => ISPAb
Pathogenesis Clinical manifestation Laboratory diagnosis Treatment and Prevention
In human: common cold (running rose), rare (viral pneumonia)

In animal: Gastroenteritis (diarrhea, hepatitis and bronchitis)

Specimen: pharyngeal swab
nasopharyngeal swab,

PCR: qRT-PCR
No specific treatment
Supportive measures
Severe cases (research drugs & therapeutics)
Avoid close contact with others, Wear a face mask, good hygiene

10. ONCOVIRUSES
Viruses may cause cancer in two ways:
1. Viral oncogene (v-onc): Region of the viral genome associated with transformation of normal cells to cancer cells. Always integrated into the host cell genome. Some
viruses can have more than one oncogene
2. Cellular proto-oncogene (c-onc): Host cellular genes involved in cellular growth control and development/differentiation in a carefully controlled manner. Not expressed
in a quiescent/dormant cell, they may become abnormally expressed when the cell is infected by tumor viruses that do not themselves carry a viral oncogene
Tumor repressor (suppressor) genes or anti-oncogenes: Transformation of normal cell to tumor cells occurs: When viral oncogenes are incorporated into the host genome;
when viral DNA is inserted near to a cellular oncogene

DNA TUMOR VIRUSES
I. Human and animal papilloma viruses: Skin and genital warts => Cancer (penis, uterus, cervix & vulva) & SCC (larynx, esophagus & skin).
II. BK virus (Human Polyoma Virus): Associated with human prostate cancer.
III. Adenoviruses: Oncogenic potential in animals not to humans.
IV. Epstein-Barr Virus (HHV 4):
 Burkitt's lymphoma: common in the tropics (more in malaria-endemic regions)
 Nasopharyngeal cancer: in China and SE Asia, where certain diets may act as co-carcinogens
• B cell lymphomas: in immune suppressed individuals
• Hodgkin's lymphoma: EBV has been detected in a high percentage (40%) of Hodgkin's lymphomas
V. Kaposi's Sarcoma Herpes Virus (HHV-8): massive proliferation of endothelial cells, hematologic malignancies primary effusion lymphoma, & various
atypical lympho-proliferative disorders.
VI. Hepatitis B Virus (HBV): HBsAg chronic carriers => hepatocellular carcinoma (HCC)
VII. Simian virus 40 (Polyoma Virus): Sarcoma in monkeys

RNA TUMOR VIRUSES
(Retroviridae)
(Retro-RNA viruses)
(Oncovirinae)
(Oncovirus)
I. Rous sarcoma Virus (RSV): Sarcoma in chicken
II. HTLV-1 (Human T-cell Lymphotropic Virus-1): Adult T-cell leukemia/lymphoma (Sezary T-cell leukemia). This disease is found in some Japanese
islands, the Caribbean, Latin America and Africa
III. HTLV-2 (Human T-cell Lymphotropic Virus-2)
• Hairy Cell Leukemia (many membrane derived protrusions that give WBCs the appearance of being “hairy”)
• The virus is endemic to very specific regions of the Americas, particularly in Native American population
 HTLV-1 and 2 transmitted by blood transfusion, sexual contact, across placenta, or through breast-feeding
IV. Mammary tumor viruses
 ONCOGENES IN RETROVIRUSES (gag, pol and env):Rous sarcoma virus (pol & onc/src), Defective transforming virus (onc), Helper virus (pol)

Retroviridae (retrovirus-RNA virus): Lentivirinae: Lentivirus: Primate Serogroup: HIV 1&2 (formerly HTLV 3)
History
AIDS was first recognized in young gay Americans with Pneumocystis carini/jervocii pneumonia and Kaposi's sarcoma (1980-1981) in NYC and San Francisco
Luc Montagier, and Robert Gallo identified HIV as a causative agent of AIDS (33 years)
Structures of HIV
I. Surface glycoproteins (gp120 and gp41)-Encoded by the env (envelope) gene
• gp120 (outer membrane part): interacts with a receptor (CD4). Remains attached to Gp41 via non- covalent bonds.
• gp41 (transmembrane part): fusogen, Fuse with host cell membrane => virus internalization. Retains the transmembrane part of Gp160.

II. Internal structural proteins (core proteins) (p17, p24, p7, p6)-Encoded by the gag (group-specific antigen) gene
• p17 (matrix protein): lines the inner surface of viral membrane & ensuring the integrity of the virion particle

11. • p24 (capsid): core protein & involved in assembly of the virus and enclosing viral RNA. p7 (nucleocapsid): coats the RNA genome & protects RNA from digestion by nucleases
III. Internal proteins (enzymes)-Encoded by the pol (polymerase) gene
• Participate in the integration of viral genome to the host cell and viral replication
 Reverse transcriptase (p66/p51): SS-RNA => SS-DNA => DS-DNA. Integrase (p32): Integrates the viral DS-DNA into the host cell chromosome
 Protease (p10): Cleaves the pol and gag-encoded polyproteins to produce matrix, capsid, nucleocapsid and p6, & enzymes (polymerase, reverse transcriptase and integrase).
Play an important role in the maturation process.
IV. The Genome of HIV (9749 nucleotides long )
 Two copies (diploid) SS (+) RNA tightly bound to nucleocapsid (p7) and enzymes (reverse transcriptase, protease and integrase)
 Three important genes encoding nine important proteins
 gag gene: internal structural proteins (4); pol gene: enzymes (3); env gene: surface glycoproteins (2)
 Other genes: nef (Negative Regulatory Factor), vif (Virion Infectivity Factor), vpr (Viral Protein R), tat (Trans-Activator of Transcription) , rev (Regulator of Virion protein
expression), vpu (Viral Protein U) => Encoding regulatory proteins (regulate viral replication)
 GAG polyproteins is cleaved to: MA (matrix, p17), CA (capsid, p24), NC (nucleocapsid, p7), & p6
 POL polyproteins is cleaved to: PR (protease, p10), RT (reverse transcriptase, p66/p51), IN (integrase, p32)
 ENV gene => translated => polyproteins (Gp160) => cleaved (by a host cell protease /furin- in Golgi body) It is not cleaved by the virus => SU (Gp120) and TM (Gp41).
HIV Types, Subgroups and Subtypes
 Types: HIV-1 (current worldwide pandemic); HIV-2 (in West Africa)
 Sub-groups: M (main / major-90%), N (new- Cameroon ) and O (outlier-Cameroon & Gabon )
 Subtypes- Ethiopia (mainly C): A & D ( C. & E. Africa), B (N. America, L. America , Caribbean, Europe, Japan & Australia), C (India & Nepal), E (Thailand & C. Africa), F (Brazil &
Romania), G (Russia & Gabon), H (Zaire & Cameroon), K (Congo & Cameroon), CRFs (A, G, H & K subtypes)
Cells that are infected by HIV
1. CD4+ (T-helper) cells (Th cells): CD4+ depletion ( lysis / killed by CD8+ cells), T4 memory cells (reservoirs for viral infection-Cellular latency)
2. CD8+ Killer T cells (cytotoxic T cells) (Tc cells): infected in small numbers by HIV in the later stages of disease
3. Natural Killer cells (NK cells)
4. Macrophages (reservoir)
5. Cells of nervous system: anti-retroviral drugs fail to penetrate the blood-brain barrier
6. Follicular Dendritic cells (FDCs): When HIV enters the body via the mucosal route => FDCs present HIV to T4 cells
7. Langerhans cells: under the skin.
HIV receptors and co-receptors
 Receptor: CD4 antigen (member of IgG super family, expressed on helper T lymphocytes, monocytes, B-lymphocytes &other cells)
 Co-receptors: Chemokine receptor (CCR5) (Transmembrane proteins): (Macrophages and Monocytes). Chemokine receptor (CXCR4) (also known as fusin): promotes the
infection/fusion of CD4+ cells: Th-lymphocytes
Life cycle of HIV (Replication of HIV)
Binding => Fusion => Uncoating => Reverse transcription (Reverse transcriptase) => Integration (integrase) => Replication (Host DNA polymerase) => Transcription (Host RNA polymerase
II) => RNA splicing (host and viral factors) => Leaving genomic RNA from the host nucleus => Genomic RNA => mRNA (Translated) => Incorporated into new virion => translation =>
Assembly (genomic RNA + internal & surface structure proteins) => Budding => Maturation
Epidemiology of HIV
MT: sex, IV drug use, blood, organ transplant, mother to child (25-53% chance). IP: 8-10/15 yrs.
Course of HIV Infection
1. Exposure to HIV
2. Acute infection (acute retroviral syndrome):Mild disease-flu-like illness resembling IMN (fever, rash, swollen lymph glands, myalgia, sore-throat) & self-limited
 Virus titer (very high - 100 million virus particles/ml plasma)
3. Window period: Seronegativity, viral load (high), exhibits some symptoms. Last for six months before seroconversion.
4. Chronic lymphadenopathy

12. 5. Asymptomatic phase (Sub-clinical-immune dysfunction) (Period of clinical latency)
6. Symptomatic phases (Skin and mucous membrane lesions)
7. AIDS (systemic/opportunistic infections): CD4+ cell count (<200 cells/cubic mm of blood)
 Opportunistic Infections:
Parasitic: Toxoplasmosis, Cryptosporidiosis, Microsporidiosis, & Isosporiasis.
Bacterial: Tuberculosis, Disseminated Mycobacterial infection (MAC), Bacterial Respiratory Infections (S. pneumoniae), Bacterial Enteric Infections (Salmonella spp.),
Fungal: Candidiasis, Cryptococcosis (brain & lung), Histoplasmosis, Coccidioidomycosis, Pneumocystis pneumonia
Viral: Cytomegalovirus Disease, Herpes Simplex Virus Disease, Herpes Zoster (shingles), Oral hairy leukoplakia (EBV)
Progressive multifocal leukoencephalopathy (JC virus), HIV encephalopathy HIV dementia", "AIDS dementia, Kaposi’s Sarcoma (HHV-8)-in of 20% AIDS patients
 AIDS-Associated Neoplasms:
Kaposi’s Sarcoma; Non-Hodgkin's lymphoma including EBV-positive Burkitt's lymphoma; Primary lymphoma of the brain
WHO-Staging of HIV
1. Clinical Stage I: Asymptomatic, Persistent Generalized Lymphadenopathy (PGL), No weight loss. Performance scale 1: asymptomatic, normal activity
2. Clinical Stage II: Weight loss, Minor mucocutaneous & other manifestations. performance scale 2: symptomatic, normal activity
3. Clinical stage III: Weight loss, other systemic/local infections. Unexplained chronic diarrhea & prolonged fever (both >1 month)
 performance scale 3: bedridden < 50% of the day during last month
4. Clinical Stage IV: HIV wasting syndrome, weight loss, unexplained chronic diarrhea & prolonged fever (> 1 month), chronic weakness. Many systemic/ opportunistic infections,
Lymphoma, Kaposi's sarcoma, HIV encephalopathy (Cognitive/motor disorder)
 Performance scale 4: bedridden > 50% of the day during last month
Indicators of Rapid progression to AIDS - Viral load & CD4 count
HIV infection diagnosis
1. HIV serology: HIV ELISA (Preliminary screening): 99.3-99.7% sensitivity. Western blot (confirmatory): 99.4-100% sensitivity. Rules out false positives. Rapid antibody tests-
(MOH algorithm-HIV screening).
 Seroconversion: Most people infected with HIV will produce enough antibodies to HIV antigens to be detectable by ELISA (i.e., seroconversion) within a 2.1months of
transmission. A ‘window’ of time exists between infection and seroconversion
 False positive test: 1:10,000. False negative test (due to early in disease /severe immunosuppression=> no antibody response)
2. p24 antigen detection: Diagnosis of neonatal HIV: maternal antibody that crosses the placental can give false positive result
 Diagnosis of HIV-window period: due to low viral load in blood => serology can give false negative result.
3. Viral load (RNA copies/ml): RT-PCR 4. Virus culture 5. CD4
+
count
HIV treatment - Recommended regimen
 HAART (highly active anti-retroviral therapy)
 Combination drugs (three or more): Synergistic, Non-cross-resistant, No overlapping toxicity
 RTI-based (2NRTI + 1NNRTI), PI-based (2NRTI+1-2 PI), Triple NRTI-based regimens.
 Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Nucleotide Reverse Transcriptase Inhibitors, Protease inhibitors (PIs), Non-nucleoside reverse transcriptase inhibitors
(NNRTIs), Fusion inhibitors (FI).
 No vaccine currently available
Post exposure prophylaxis (PEP) HIV
• Should be started within 24-48 hrs (within 1-2 hrs) & continued for 28 days. PEP have 75-80% efficacy.
• Don’t consider PEP beyond 72 hours post exposure
 Follow-up : HIV testing – at the time of exposure and again at 6
th
week, 3
rd
month & 6
th
month
Assessment of exposure risk for HIV
Low-risk (injury with a solid needle) & High-risk (Injury with a hollow needle)