Herpes virus

OM VERMA
ASSISTANT PROFESSOR
RELIANCE INSTITUTE OF NURSING DHAMTARI

2. herpes virusinfections
PRESENTED BY-
OMVERMA
ASSISTANT PROFESSOR
RELIANCE INSTITUTEOF NURSING
DHAMTARI

3. INTRODUCTION
They are known as the humanherpesvirusesand
are herpes simplex virus type 1, herpes simplex
virus type 2, varicella-zoster virus,
cytomegalovirus, Epstein-Barr virus,
humanherpesvirus6, humanherpesvirus7 and,
most recently, Kaposi's Sarcomaherpesvirus.

4. Herpesviruses
•These are enveloped viruses (100 nm in diameter) with an
icosahedral nucleocapsid and double-stranded linearDNA.
•They are noted for causing latentinfections.
•The five important human pathogens
are
•1.Herpes Simplex Virus types 1 and 2
2.Varicella-ZosterVirus
3. Cytomegalovirus
4.Epstein–Barr Virus (the cause of
Infectiousmononucleosis).

5. 1.HERPES SIMPLEX VIRUS
The herpes simplex virus, also known as HSV, is an
infection that causes herpes. Herpes can appear in
various parts of the body, most commonly on the genitals
or mouth. There are two types of the herpes simplex
virus.
HSV-1:primarily causes oral herpes, and is generally
responsible for cold sores and fever blisters around the
mouth and on the face.
HSV-2:primarily causes genital herpes, and is generally
responsible for genital herpes outbreaks.

6. HERPES SIMPLEXVIRUSES
•extremely widespread in the humanpopulation.
•broad hostrange
•being able to replicate in many types of cells and to infect many differentanimals.
•They grow rapidly and are highlycytolytic.
•The herpes simplex viruses are responsible for a spectrum of diseases, ranging from
gingivostomatitis to keratoconjunctivitis, encephalitis, genital disease, and infections of
newborns.
•The herpes simplex viruses establish latent infections in nerve cells; recurrences arecommon.
PROPERTIES OF HERPES SIMPLEXVIRUS
•Genome sequence of HSV-1 and HSV-2 are same but canbe
distinguished by sequence analysis or by restriction enzyme
analysis
•HSV-1 is spread by contact, usually involving infected saliva,
whereas HSV-2 is transmitted sexually or from a maternal
genital infection to anewborn
•Growth cycle proceeds rapidly, requiring 8–16 hoursfor
completion
•Genome is large (about 150 kbp), encode at least 70
polypeptides; functions of many of the proteins in replication
or latency are notknown

7. HSV-1 ETIOLOGY
can be contracted from general interactions such as:
eating from the same utensils
sharing lip balm
Kissing
The virus spreads more quickly when an infected person is
experiencing an outbreak. An estimated67 percent Trusted
Sourceof people ages 49 or younger are seropositivefor HSV-
1, though they may never experience an outbreak. It’s also
possible to get genital herpes from HSV-1 if someone who
performed oral sex had cold sores during that time.

8. HSV-2
HSV-2 is contracted through forms of sexual contact
with a person who has HSV-2. An estimated 20
percent of sexually active adults in the United States
are infected with HSV-2, according to theAmerican
Academy of Dermatology (AAD). HSV-2 infections are
spread through contact with a herpes sore. In
contrast, most people get HSV-1 from an infected
person who is asymptomatic, or does not have sores.

9. Pathogenesis
Cytolyticinfectiousnecrosisofinfectedcellstogetherwiththeinflammatoryresponse
LesionsinducedbyHSV-1andHSV-2arethe same,resemblingthoseof varicella-zostervirus
Characteristic histopathologic changes include ballooning of infected cells, production of Cowdry
type A intranuclear inclusion bodies, margination of chromatin and formation of multinucleated
giantcells
Cell fusion provides an efficient method for cell-to-cell spread ofHSV
A. PRIMARYINFECTION
transmitted by contact of a susceptible person with an individual excretingvirus
Thevirusmustencountermucosalsurfacesorbrokenskininorderfor aninfectiontobeinitiated
(unbroken skin isresistant).
HSV-1infectionsareusuallylimitedtotheoropharynx,andvirusisspreadby respiratorydroplets
or by direct contact with infectedsaliva.
HSV-2 is usually transmitted by genitalroutes.
Viralreplicationoccursfirstat the siteof infection. Virusthen invadeslocalnerveendingsandis
transported by retrograde axonalflow
Primary HSV infections are usually mild; in fact, most are asymptomatic. Only rarely doessystemic
diseasedevelop.
Widespread organ involvement can result when an immunocompromised host is not able tolimit
viral replication and viremiaensues.

10. B. LATENTINFECTION
Virus resides in latently infected ganglia in a nonreplicating state; only a very few viral genesare
expressed.
A smallRNA,calledamicroRNAworkstopreventcelldeath,maintainingthelatentinfection.
Viralpersistenceinlatentlyinfectedganglialastsforthelifetimeofthehost.
Noviruscanberecoveredbetweenrecurrencesator neartheusualsite ofrecurrentlesions.
Reactivation of virus from the latent state by axonal injury, fever, physical or emotional stress,and
exposure to ultravioletlight
Humoral and cellularimmunity in the host limits local viral replication, so that recurrent infections
are less extensive and less severe. Many recurrences are asymptomatic, reflected only by viral
shedding insecretions
Whensymptomatic,episodesofrecurrentHSV-1infectionareusuallymanifestedascoldsores
(fever blisters) near thelip.
Morethan80%ofthehumanpopulationharborHSV-1inalatentform,butonly asmallportion
experiencerecurrences

11. Symptoms
A. OROPHARYNGEALDISEASE
•Symptomatic disease
•most frequently in small children (1–5 years ofage)
•involves the buccal and gingival mucosa of themouth
•Incubation period is short (about 3–5 days, with a rangeof
2–12days)
•clinical illness: lasts 2–3weeks.
•Symptoms include fever, sore throat, vesicular and ulcerative
lesions, gingivostomatitis, and malaise. Gingivitis (swollen,
tendergums)isthemoststrikingandcommonlesion.
•Primary infectionsin adults commonly cause pharyngitis
and tonsillitis. Localized lymphadenopathy mayoccur.
•Recurrent diseaseis characterized by a cluster ofvesicles
most commonly localized at the border of thelip
•Intense pain occurs at the onset but fades over 4–5days.
Lesions progress through the pustular and crusting stages,
and healing without scarring is usually complete in 8–10
days.
•The lesions may recur, repeatedly and at various intervals,
in the samelocation
Herpes simplex
gingivostomatitis
Recurrent herpessimplex
labialis

12. •B.KERATOCONJUNCTIVITIS
•HSV-1 infections in the eye producesevere
keratoconjunctivitis.
•Recurrent lesions of the eye are common and
appear as dendritic keratitis or corneal ulcers oras
vesicles on the eyelids progressive involvement of
the corneal stroma, with permanent opacification
andblindness.
•HSV-1 infections are second only to trauma as a
cause of corneal blindness in the UnitedStates.
C.ENCEPHALITIS
HSV-1 infections are considered the most common
cause of sporadic, fatal encephalitis in the United
States.
High mortalityrate
Survivors often have residual neurologicdefects.
About half of patients appear to have primary
infections, and the rest appear to have recurrent
infection.
(A) Herpes simplex virus 1 (HSV-1) encephalitis:T2-
weighted MRI brain scan demonstrates bilateral
involvement of temporallobes.

13. D. GENITALHERPES
•Usually caused by HSV-2, but HSV-1 can also cause genitalherpes.
•Primary genital herpes infections can be severe, with ill-ness lasting about 3weeks.
•Characterized by vesiculoulcerative lesions of the penis of the male or of the cervix, vulva,
vagina, and perineum of the female. The lesions are very painful and may be associated with
fever, malaise, dysuria, and inguinal lymphadenopathy. Complications includeextragenital
lesions (≈ 20% of cases) and aseptic meningitis (≈ 10% ofcases).
•Viral excretion persists for about 3weeks.
•Because of the antigenic cross-reactivity between HSV-1 and HSV-2, pre-existing immunity
provides some protection against heterotypic infection. An initial HSV-2 infection in a person
already immune to HSV-1 tends to be lesssevere.
•Recurrencesare common and milder. A limited number of vesicles appear and heal in about
10 days. Virus is shed for only a few days (a person shedding virus can transmit the infection to
sexualpartners).

14. E. INFECTIONSIN
IMMUNOCOMPROMISED HOSTS
•Are at increased risk ofdeveloping
severe HSVinfections.
•Include patients
immunosuppressed by diseaseor
therapy (especially those with
deficient cellular immunity)
malnourished
•Renal, cardiac, and bone marrow
transplant recipients, with
hematologic malignancies andAIDS
•Herpes lesions may spread and
involve the respiratory tract,
oesophagus, and intestinal
mucosa. Malnourished childrenare
prone to fatal disseminated HSV
infections.
F. SKININFECTIONS
•Intact skin is resistant to HSV, so cutaneousHSV
infections are uncommon in healthypersons.
•Localized lesions caused by HSV-1 or HSV-2 may
occur in abrasions that become contaminated with
thevirus(traumatic herpes).Theselesions areseen
on the fingers of dentists and hospital personnel
(herpetic whitlow) and on the bodies of wrestlers
(herpesgladiatorum).
•Severe and life threatening when they occur in
individuals with disorders of the skin, such as
eczema or burns, that permit extensive localviral
replication andspread.
•Eczema herpeticum is a primary infection,usually
withHSV-1,inapersonwithchroniceczema.
•In rare instances, the illness may befatal.
Herpetic
Whitlow

15. •G. NEONATALHERPES
•Infection of the newborn acquired in utero, during birth, or after
birth.
•The newborn infant seems to be unable to limit the replication and
spread of HSV and has a propensity to develop severedisease.
•Route of infection (≈ 75% of cases)-transmitted during birth by
contact with herpetic lesions in the birth canal acquired postnatal by
exposure to either HSV-1 or HSV-2 (1 in 5000 peryr).
•Avoided by delivery by caesarean section has been used in
pregnant women with genital herpeslesions.
•Sources of infection-family members and hospital personnel
sheddingvirus.
•About 75% of neonatal herpes infections are caused byHSV-2.
•Symptomatic.
•The overall mortality rate of untreated disease is 50%.
•Babies with neonatal herpes exhibit three categories ofdisease:
•(1)Lesions localized to the skin, eye, andMouth;
•(2) Encephalitis with or without localized skininvolvement;
•(3) Disseminated disease involving multiple organs, including the
central nervous system(the worst prognosis, mortality rate about
80%) cause of death being usually viral pneumonitis or
intravascular coagulopathy. Many survivors of severe infections
are left with permanent neurologicimpairment.
NEONATALHERPES

16. LABORATORYDIAGNOSIS
A.CYTOPATHOLOGY-stain scrapings from the base of a vesicle (eg, with Giemsa’sstain)
B.ISOLATION AND IDENTIFICATION OF VIRUS-lesions, throat washings, cerebrospinal
fluid, and stool, both during primary infection and during asymptomatic periods. Then
identified by Nt test or immunofluorescence staining with specific antiserum. Typing done
using monoclonal antibody or by restrictionendonuclease
C.POLYMERASE CHAIN REACTION (PCR) of viral DNA from cerebrospinalfluid.
D.SEROLOGY-Antibodies appear in 4–7 days after infection and reach a peak in 2–4 weeks.
They persist for the life of the host. Limited by the multiple antigens shared by HSV-1 and HSV-2.
There may also be some heterotypic anamnestic responses to varicella-zoster virus in persons
infected with HSV, and viceversa.

17. Epidemiology
•Worldwide indistribution.
•No animal reservoirs or vectors areinvolved
•Transmission -by contact withinfected
secretions.
•HSV-1 Primary infection occurs early in life
and is usually asymptomatic. Antibodies
develop, a carrier state is established thatlasts
throughout life and is punctuated by transient
recurrent attacks ofherpes.
•Highest incidence of HSV-1 -children 6
months to 3 years of age. By adulthood,70–
90% of persons have type 1antibodies.
•Middle-class individuals in developed
countries acquire antibodies later in lifethan
lower socioeconomicpopulations

18. HSV-2isusuallyacquiredasasexuallytransmitteddisease,soantibodiestothisvirusare
seldom found before puberty. Estimated 40–60 million infected individuals in theUS.
•20% of adults in the US possess HSV-2 antibodies, with seroprevalence higheramong
women than men and higher among blacks thanwhites.
•Recurrentgenitalinfectionsmaybesymptomaticor asymptomatic.Eithersituationprovides
a reservoir of virus for transmission to susceptiblepersons.
•HSV-2 tends to recur more often than HSV-1, irrespective of the site ofinfection.

19. Treatment, Prevention, &Control
•Antiviral drugs acyclovir, valacyclovir, andvidarabine.
•Acyclovir is currently the standard therapy.All are inhibitorsof viral DNA
synthesis.
•The drugs may suppress clinical manifestations, shorten time to healing, andreduce
recurrences of genitalherpes.
•Drug-resistant virus strains mayemerge.
•Newborns and persons with eczema should be protected from exposure topersons
with active herpeticlesions.
•Experimental vaccines of various types are beingdeveloped.
Vidarabine

20. VARICELLA-ZOSTERVIRUS

21. Varicella-zoster virus(VZV) is the cause of
chickenpox and herpeszoster(also called
shingles). Chickenpox follows initial exposure to
thevirusand is typically a relatively mild, self-
limited childhood illness with a characteristic
exanthem.
Diseases or conditions caused:Chickenpox;
Shingles; Encephalitis

25. VARICELLA-ZOSTERVIRUS
Varicella (chickenpox) is a mild, highly contagious disease, chieflyof
children, characterized clinically by a generalized vesicular eruption
of the skin and mucous membranes. The disease may be severe in
adults and in immunocompromisedchildren.
Zoster (shingles) is a sporadic, incapacitating disease of adultsor
immunocompromised individuals that is characterized by a rash
limited in distribution to the skin supplied by a single sensory
ganglion. The lesions are similar to those ofvaricella.

26. ETIOLOGY

42. OM VERMA

43. OM VERMA

44. CYTOMEGALOVIRUS
•The name for the classic cytomegalic inclusion disease derives from the propensityfor
massive enlargement of cytomegalovirus-infectedcells.
•Cytomegalic inclusion disease is a generalized infection of infants causedby
intrauterine or early postnatal infection with thecytomegaloviruses.
•Severe infections in adults who areimmunosuppressed.
Massively enlarged “cytomegalic” cells typical of
cytomegalovirus infection present in the lung of a premature
infant who died of disseminated cytomegalovirusdisease

45. OM VERMA

46. Properties of theVirus
largest genetic content DNA genome (240 kbp) and 200proteins
Cell surface glycoprotein, Fc receptor bind nonspecifically to Fc portion of antibody & help
infected cells evade immuneelimination
The major immediate early promoter-enhancer is used experimentally to support high-level
expression of foreigngenes.
Replicates in vitro only in human fibroblasts, although often isolated from epithelial cells of
the host.
Replicates very slowly in culturedcells
Very little virus becomes cell-free; infection is spread primarilycell-to-cell.
Takes several weeks for an entire monolayer of cultured cells to becomeinvolved.
Characteristic cytopathic effect-Perinuclear cytoplasmic inclusions form in addition to the
intranuclear inclusions typical of herpesviruses(multinucleated cells are seen andbecome
greatlyenlarged.
Typical "owl
eye"inclusion
indicating
CMVinfection
of a lung
pneumocyte

47. Pathogenesis
•transmitted person-to-person requiringclose
contact with virus-bearingmaterial
•4-to 8-week incubationperiod
•The disease is an infectious mononucleosis-like
syndrome mostlysubclinical

48. Symptoms
•malaise, myalgia, protracted fever, liver function
abnormalities, andlymphocytosis
•Subclinical hepatitis iscommon
•Pneumonia is a frequent complication (bone
marrow transplantrecipients)
•result in death of the fetus in utero , survivors
develop significant CNS defects within 2 years;
severe hearing loss, ocular abnormalities,
deafness, and mental retardation arecommon

49. OM VERMA

50. LaboratoryDiagnosis
•PCR and Antigen detectionassays
•Isolation ofVirus
•Serological testing-IgG-Past Infection
-IgM-CurrentInfection

51. Treatment andControl
Severity of cytomegalovirus is reduced by
ganciclovir
Foscarnet -cytomegalovirusretinitis.
Acyclovir and valacyclovir -in bonemarrow
and renal transplantpatients.
Isolation of newborns infected from other
newborns
Screening of transplant donorsand
recipients for cytomegalovirusantibody
Epidemiology
•Endemicworldwide
I.Throughout the year
II.Prevalence varies with socioeconomic status, living conditions,and
hygienicpractices
III.Humans are the only knownhost
IV.Transmission requires close person-to-personcontact

53. Epstein-BarrVirus
•The major target cell for EBV is theB
lymphocyte immortalizing thecells
•. There are two types (EBV-1, EBV-2),
based on differences in the latency
nuclear antigen genes (EBNAs,EBERs).
•EBV directly enters a latent state in the
lymphocyte without undergoing a
period of complete viralreplication
•Viral antigens include latent antigens,
early antigens and lateantigens

54. ETIOLOGY

58. •1. Primary Infection-Initiates infection in the
oropharynx
•Viral replication occurs in epithelial cells (or
surface B lymphocytes) of the pharynx and
salivaryglands
•Infected B cells spread the infection from the
oropharynx throughout thebody.
•In young adults acute infectious mononucleosis
(polyclonal stimulation of lymphocytes) often
develops.
•2. Reactivation-Evidenced by increased levels of
virus in saliva and of DNA in bloodcells
•3. Cancer-Burkitt’s lymphoma,
nasopharyngeal carcinoma, Hodgkin’s
disease.

59. Symptoms
A. INFECTIOUS MONONUCLEOSIS
headache, fever, malaise, fatigue,and
sore throatoccur.
Enlarged lymph nodes,spleen,hepatitis.
IncreasedWBCs
•B. ORAL HAIRY LEUKOPLAKIA in HIV-
infected persons and transplantpatients.
•C.BURKITT’SLYMPHOMA(a tumourof
the jaw in African children and young
adults)..
•D.NASOPHARYNGEALCARCINOMAin
males of Chineseorigin.
Oral HairyLeukoplakia
NasopharyngealCarcinoma

62. LaboratoryDiagnosis
•ISOLATION AND IDENTIFICATION OF VIRUS BY
NUCLEIC ACIDHYBRIDIZATION
•SEROLOGYELISA tests, immunoblotassays,
and indirect immunofluorescencetests
•IgM type-currentinfection.
•IgG -past infection and indicatesimmunity.

63. Epidemiology
Common in all parts of theworld
100,000 cases of infectious mononucleosis annuallyin
theUS
Developing areas>90% of children infected by age6.
Industrialized nations>50% infections are delayeduntil
late adolescence and youngadulthood
Treatment, Prevention andControl
No vaccineavailable.
Acyclovir reduces EBV shedding from the oropharynx ,
but does not affect the number of EBV-immortalized B
cells,and
No treatment for Immunocompromisedpatients.

64. Cytopathic effects induced by herpesviruses. A: Herpes simplexvirus
B: Varicella-zoster virus in human kidneycells
C: Cytomegalovirus in human fibroblasts
D: Cytomegalovirus in humanfibroblasts