Herpesviruses S Munsaka

Herpesviruses
Medical Microbiology; PTM 4310

MBCHB Programme
S. M. Munsaka, BSc., MSc.,PhD

Department of Biomedical Sciences, School of Health Sciences
Department of Pathology and Microbiology
School of Medicine
The University of Zambia
26th May 2020

Herpesviridae (Herpesviruses)
 Herpesviridae (Herpesviruses) include: Herpes simplex, herpes

zoster, Herpes virus 8 (Kaposi sarcoma-associated herpesvirus)
cytomegalovirus (CMV), Epstein-Barr virus (EBV)
 Double stranded DNA viruses

Linear dsDNA genomes
 Enveloped polyhedral viruses (150-250nm)
 Replicate in the nucleus, encapsulation occurs in the nucleus and

membrane is acquired on budding
 Medium sized viruses, cause chickenpox, shingles, Burkitt's

lymphoma, infectious mononucleosis, CMV causes pneumonia and
brain lesions in immunocompromised individuals, EBV causes
Burkitt’s lymphoma.
Herpesviruses (Herpesviridae)
 All Herpesviruses have capacity to persist in their host indefinitely (chronic

infection)
Double stranded DNA persist as nuclear episomes (unintegrated DNA)
Varicella-Zoster virus (chickenpox) and herpes simplex viruses establish latent

infection in neurons
On reactivation Varicella causes herpes zoster (shingles) and chickenpox; herpes

simplex type 1 causes labial herpes, herpes simplex type 2 is responsible for genital
herpes.
Cytomegalovirus (CMV), Epstein-Bar virus (EBV) and human herpes virus type 6
(HHV-6) cause chronic infections in lymphocytes
 EBV causes infectious mononucleosis and is associated with some cancers, carcinoma and
lymphoma.
 HHV-6 causes numerous skin rashes in children
 Increasing important because of HIV/AIDS and immunosuppression for organ

transplant or cancer treatment
Human Herpesviruses
Subfamily/genus Official name Vernacular name Biological properties

Alphaherpesvirinae
Herpes simplexvirus Human herpesvirus 1 Herpes simplex virus 1
Human herpesvirus 2 Herpes simplex virus 2
Cercopithecine Simian herpes B virus Fast growing, cytolitic and latent
Herpesvirus 1 in neurons
Varicellovirus Human herpes virus 3 Varicella-zoster virus
Betaherpesvirinae
Cytomegalovirus Human herpesvirus 5 Cytomegalovirus Slow growing, cytomegallic, latent in
salivary glands, kidneys
Latent in macrophages and

Roseolovirus Human herpesvirus 6 lymphocytes
Gammaherpesvirinae
Lymphocryptovirus Human herpesvirus 4 Epstein-Barr virus Lymphoproliferative, latent in B
lymphocytes
Human Herpesvirus 8 Kaposi sarcoma-associated
herpesvirus (HHV8)
Herpes simplex viruses
 Responsible for a wide range of disease including
gingivostomatitis, keratoconjuctivitis, encephalitis,
genital disease, disease in neonates
 HSV establishes latent infections in nerve cells

and recurrences are common
 Causes cytolic infections

Pathology associated with necrosis and inflammation
Similar to varicella zoster disease
Primary infection
 Transmission is by contact (mucosal surfaces or
broken skin, droplets or saliva)
 Initial replication in the oropharynx but virus

infects local nerve ending and is transported to
the CNS (dorsal root ganglia) by retrograde
axonal transport (to establish latency)
 Disease is mild and often asymptomatic

Viremia occurs in immunocompromised individuals
Latent infection
 Virus in dorasl root ganglia (non-replicating)
 Reactivation: virus takes axonal root to the

periphery
 Manifestations include cold sores near the lip

Diagnosis
 PCR
 Virus isolation
 Cytopathology
Giemsa stain
 Serology
EIA
Treatment
 Inhibitors of DNA polymerase
Acyclovir
Cytomegalovirus (CMV)
 Ubiquitous herpesvirus
Most common cause of congenital infection
Disease ranges from generalized infection
Severe disease is found in immunocompromised
adults
 Properties
Largest genetic content of all human Herpesviruses
Very species specific
Replicates in fibroblasts and epithelial cells
Cytopathic effect: cell enlargement
Transmission
 Close contact
 Incubation period of 4-8 wks
 Causes systemic infection

Causes infectious mononucleosis-like disease
Most infections are subclinical
Virus shed in urine and from pharynx
Establishes latent infection
Dampens cell mediated immunity and allows for viral persistence
Pneumonia is the most common symptom in
immunocompromised patients
Epstein –Barr Virus
 Main cause of acute infectious mononucleosis
 Associated with pharyngeal carcinoma, Burkitt

lymphoma, Hodgkin's and non-Hodgkin’s
lymphoma and other lymphoproliferative
disorders, and gastric carcinoma
 Infections B cells (transforms/immortalizes B

cells)
 Establishes latency and reactivation is common

in immunocompromised individuals
Human Herpesvirus 8 (HHV8)
 First identifies in 1994 in Kaposi sarcoma specimens
Kaposi sarcoma herpesvirus (KSHV)
 KSHV is lymphotropic
 KSHV is responsible for KS, vascular tumours and body

cavity-based lymphomas
 Transmission is through sexual intercourse, vertically, blood

and organ transplants, and contact of oral fluids
 Incidence of KS has reduced in HIV-infected patients on

cART
Varicella-zoster virus
 Varicella-zoster virus causes two almost universal human
diseases:
Varicella (chickenpox), a childhood exathem and herpes zoster
(shingles), a disabling disease of aged person or
immunocompromised individuals
 Pathogenesis and immunity

Virus enters by inhalation and replicates respiratory mucosa
Incubation period of 10-20 days
Dissemination occurs via mononuclear leukocytes and
endothelial cells
Rash result from multiplication of virus in epithelial cells in the
skin.
Herpes zoster occurs when Varicella virus in sensory ganglion is
reactivated and descends the sensory nerve within the axon.
 Decline in cell-mediated immunity is thought to precipitate herpes
zoster attacks
Varicella (chickenpox)
 Rash happens suddenly with or without fever
 Eruption occurs on the trunk then spreads to head and limbs
 Very itchy lesions (scratching); can lead to secondary bacterial infection
 Painful ulcerating vesicles may develop in mucous membranes (mouth or

vulva)
 Neurological complication are rare but more serious (1:1000 develop

encephalitis, other complications include Guillain-Barre syndrome and
Reye’s syndrome)
 Disease may be disseminated to lungs (pneumonia), liver and brain

Disease is severe in women with primary infection and infants born to mother who
had no previous infection (no maternal antibodies against Varicella)
VARICELLA (CHICKENPOX)
Herpes Zoster
 Results from reactivation of virus in the sensory ganglion

following attack of chickenpox many years earlier
 Vesicles are usually unilateral and confined to area of the skin

innervated by particular sensory ganglion (zoster, gird le) on
the trunk or face involving the eye, scattered lesions outside
the dermatome may occur
 Pan is often severe for up to a few weeks but neuralgia may

persist for months
 Motor paralysis and encephalomyelitis are rare complications
 Disseminated disease may be seen in cancer patients or

immunocompromised patients
HERPES ZOSTER
Diagnosis
 Clinical features of Varicella and herpes zoster are so

distinctive that laboratory diagnosis is rare
 Microscopy using skin smears to demonstrate characteristic

intranuclear inclusions within multinucleated giant cells
Or use of monoclonal fluorescent antibody
 EIA to demonstrate Varicella virus antigens
 PCR can be used to amplify Varicella DNA isolated from

virions in the vesicle fluid.
 Recent infection can be confirmed by rising titer of IgM using

EIA
Epidemiology and control
 Varicella occurs throughout the year but most prevalent in late winter and spring
 Epidemic occur among susceptible children (schools and hospitals)
 Passive immunization: zoster immunoglobulin from convalescent zoster patients

Given to nonimmune pregnant woman or immunocompromised individuals who come into
contact with Varicella within 3 days.
 Active immunization (vaccination): live attenuated vaccine from attenuated Oka

strain of Varicella virus (made by serial passage in cultured human and guinea pig
fibroblasts); protection is lower in children and immunocompromised patients. Vaccine
strain may establish latent infection in the dorsal ganglia and get reactivated later on
causing zoster but this reactivation is rare following natural varicella infection.
 Chemotherapy:
Can be managed by prevention of secondary bacterial infection
Pneumonitis or herpes zoster involving the eye needs treatment with intravenous or oral
acyclovir

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Herpesviruses

Medical Microbiology; PTM 4310

S. M. Munsaka, BSc., MSc.,PhD

26th May 2020

 Herpesviridae (Herpesviruses) include: Herpes simplex, herpes

 Double stranded DNA viruses

 Enveloped polyhedral viruses (150-250nm)

 Replicate in the nucleus, encapsulation occurs in the nucleus and

 Medium sized viruses, cause chickenpox, shingles, Burkitt's

 All Herpesviruses have capacity to persist in their host indefinitely (chronic

Double stranded DNA persist as nuclear episomes (unintegrated DNA)

Varicella-Zoster virus (chickenpox) and herpes simplex viruses establish latent

On reactivation Varicella causes herpes zoster (shingles) and chickenpox; herpes

 Increasing important because of HIV/AIDS and immunosuppression for organ

Subfamily/genus Official name Vernacular name Biological properties

Varicellovirus Human herpes virus 3 Varicella-zoster virus

Latent in macrophages and

 HSV establishes latent infections in nerve cells

 Causes cytolic infections

 Initial replication in the oropharynx but virus

 Disease is mild and often asymptomatic

 Reactivation: virus takes axonal root to the

 Manifestations include cold sores near the lip

 Incubation period of 4-8 wks

 Causes systemic infection

 Main cause of acute infectious mononucleosis

 Associated with pharyngeal carcinoma, Burkitt

 Infections B cells (transforms/immortalizes B

 Establishes latency and reactivation is common

 KSHV is responsible for KS, vascular tumours and body

 Transmission is through sexual intercourse, vertically, blood

 Incidence of KS has reduced in HIV-infected patients on

 Pathogenesis and immunity

 Rash happens suddenly with or without fever

 Eruption occurs on the trunk then spreads to head and limbs

 Very itchy lesions (scratching); can lead to secondary bacterial infection

 Painful ulcerating vesicles may develop in mucous membranes (mouth or

 Neurological complication are rare but more serious (1:1000 develop

 Disease may be disseminated to lungs (pneumonia), liver and brain

 Results from reactivation of virus in the sensory ganglion

 Vesicles are usually unilateral and confined to area of the skin

 Pan is often severe for up to a few weeks but neuralgia may

 Motor paralysis and encephalomyelitis are rare complications

 Disseminated disease may be seen in cancer patients or

 Clinical features of Varicella and herpes zoster are so

 Microscopy using skin smears to demonstrate characteristic

 EIA to demonstrate Varicella virus antigens

 PCR can be used to amplify Varicella DNA isolated from

 Recent infection can be confirmed by rising titer of IgM using

 Epidemic occur among susceptible children (schools and hospitals)

 Passive immunization: zoster immunoglobulin from convalescent zoster patients

 Active immunization (vaccination): live attenuated vaccine from attenuated Oka

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