13.Herpesviridae.ppt

There are nearly 100 viruses of the herpes group that infect many different animal species.
Official name of herpesviruses that commonly infect human is Humans herpesvirus (HHV)
herpes simplex virus types 1 (HHV 1)
Herpes simplex virus type 2 (HHV 2)
Varicella-zoster virus (HHV 3)
Epstein-Barr virus, (HHV 4)
Cytomegalovirus (HHV 5)
Human herpesvirus 6 (HHV 6)
Human herpesvirus 7 (HHV 7)
Human herpesvirus 8 (HHV 8) (Kaposi's sarcoma-associated herpesvirus).
Herpes B virus of monkeys can also infect humans
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1. Herpesviridae
DR.HAMISI MKINDI,MD.
TO DOWNLOAD CONTACT: [email protected]

2. Introduction
•Leading cause of human viral disease.
•25 viruses in the family Herpesviridae
•Three sub-families
•Eight are known to infect Human
•Infection remains for life

6. Virology
•Herpes viruses are enveloped viruses
•Capsomere of about 100-200 nm
•Icosahedral nucleocapsid
•Contains 162 capsomeres
•Double stranded DNA

7. Replication

8. Replication
•RNA transcription: cellular enzyme (DNA-
dependent RNA polymerase I).
•DNA synthesis: Herpes viruses encode
their own DNA-dependent DNA
polymerase. Other enzyme (such as
thymidine kinase)
•Assembly: Nucleocapsids are assembled
in the nucleus.

9. Proteins
•Alpha proteins: These are the immediate-
early proteins.
•Beta proteins. Involved also in DNA
replication (DNA polymerase and
transcription factors).
•Gamma proteins. Late proteins are
structural components of the virus.

10. Herpes simplex Virus (HSV)
•HSV-1
•HSV-2

11. Pathogenesis
•Transmission: Close contact
•Infect epithelial mucosal cells or
lymphocytes: receptors gB and gD
•Travels up peripheral nerves to a ganglion
•Herpes simplex 1 and 2 can infect both
humans and other animals
•

12. Immune escape
•gC, gE and gI).
•gC which binds complement C3 and Fc

13. Immune response
•Neutralizing IgG may be present
throughout life
•Complement-mediated lysis of infected
cells
•Cytotoxic T-lymphocytes, NK cells and
macrophages in acute and in recurrent
infections

14. Reactivation
•Immunosuppression
•Stress
•Trauma
•Ultraviolet radiation
•Fever

15. Clinical diseases
•Oral herpes -Cold sores
•Herpes keratitis
•Herpes whitlow
•Neonatal herpes
•Genital herpes
•HSV Encephalitis
•HSV meningitis

21. Varicella-Zoster Virus
•Human Herpes Virus-3
•Two diseases: Chickenpox (Varicella) and
shingles (Zoster)

22. Pathogenesis and Immnunity
•Inhalation
•Replicates in the mucosa of respiratory
tract.
•Dissemination lymphatics and blood
stream
•Multiplication: Endothelial cells, monocytes
•Multiplication in the epithelial cells Lead to
rashes

23. Cont
•Virus ascend the axons of sensory nerves.
•Localized on sensory ganglia
•It becomes latent for life time.
•Infection is controlled by T cell mediated
immunity
•Reactivation: Shingles
•10-20% of previously infected.

24. Chickenpox (Varicella)
•More than 90% of US have antibodies
•Highly infectious
•Lesions on the trunk, spread to heads and
limbs
•Itchy lesions
•1 in 1000 get neurological complication

25. Herpes Zoster
•Results from reactivation of virus
•Vesicles are unilateral (confined to the
area innervated by sensory ganglion
(Zoster, girdle)
•Trunk, face

27. Laboratory diagnosis
•Clinical
•Specimen: smears from the base of early
skin lesion, Vesicle fluid
Monoclonal fluorescent antibody
EIA
PCR
Culture on Human lung embryonic
fibroblast, CPE after 2 weeks or more.

28. Treatment and control
•Acyclovir ( prevent dissemination in
immunosuppressed patients.
•Varicella immunoglobulin
•Vaccine There is a live attenuated
vaccine.

29. Epstein-Barr Virus
•Causative agent:
Burkitt's lymphoma,
Nasal pharyngeal carcinoma
Infectious mononucleosis

30. Infectious Mononucleosis
•An acute d’se x’zed by fever and swollen
lymph nodes and abnormal increase of
mononuclear leucocytes or monocytes in
the bloodstream;not highly
contagious;believed to be transmitted
through kissing

31. Receptors for the virus
•Infects cell types that express the receptor
for complement C3d component (CR2 or
CD21). T
epithelial cells (oro-and naso-pharynx)
B lymphocytes.
(cellular tropism)

32. Pathogenesis
•Transformation of B cells
Genome persist as plasmid
EBNA-2 is expressed
It immortalizes the B cell
Depression of Cell mediated immunity (IL-
10 analog)
•Burkitt's lymphoma
Translocation between chromosomes 8 and
14 brings c-myc near IG promoter

33. Infectious mononucleosis
Glandular fever
•Presents 1-2 months of infection.
•Characterized by
malaise,
lymphadenopathy,
tonsillitis
enlarged spleen and liver.
fever

34. Lab Diagnosis
•Heterophile antibodies (IgM agglutinate
sheep RBC
•EBV specific antibodies

35. CMV
•Largest genome of herpes viruses and
appears only to replicate in human cells.
•Form multinucleated cells (syncytia)
•Latent infection : T lymphocytes and
stromal cells of the bone marrow.
•There is only one serotype

36. Pathogenesis
•Once infected individual carry it for life.
•Intermittently shed in Saliva, urine, semen
and cervical secretions, breast milk.
•Reactivation occurs:
Pregnancy
Immunosuppression (AIDS
•Pathogenesis and latency mechanisms
are not known

37. Congenital disease
•During a primary infection of the mother,
congenital abnormalities
microcephaly,
rash,
brain calcification
hepatosplenomegaly.
hearing loss
Retardation..

38. Cont
•Perinatal infection of the newborn or
infants
•

39. Disease in immunosuppressed patients
Organ transplant
Immunosuppressive disease (e.g. AIDS),
•cytomegalovirus can be a major problem.
cytomegalovirus-retinitis 15% of AIDS.,
interstitial pneumonia,
colitis,
esophagitis
encephalitis.

40. Lab Diagnosis
•Culture
•Fluorescent stain
•PCR
•DNA hybridization
•EIA

41. HHV 6
•Found worldwide and is
•Found in the saliva of the majority of adults
(>90%)
•All children by the age of two are infected and
the infection is life-long
•Replicates in
–B and T lymphocytes,
–megakaryocytes,
–glioblastoma cell
–oropharynx.
latent infection in T cells

42. Clinical diseases
•Rashes
•Lymphadenopathy
•Encephalopathy

43. HHV-7
•Binds to the CD4 antigen
•Replicates in T4 (CD4+) cells
•Found in the saliva of the majority of the
adult population (>75%).
•Infection as children.
•Cases of exanthema subitum

44. HHV-8
•Subfamily: Gammaherpesvirinae
•Identified in 1994
•140kbp
•Transmission Sexually, or non sexual route
•Molecular type: A, B,C 3% nucleotide variability
•K1 gene ecodes transmembrane glycosylated
protein