February 18, 2014 HERPESVIRUSES Herpesviruses that commonly infect humans: Herpes simples virus types 1 and 2 Varicella-

a- zoster virus Cytomegalovirus Epstein-Barr virus Herpesvirus 6 and 7 Herpesvirus 8 (Kaposis sarcoma-associated Herpesvirus) Herpes B virus of monkeys (Macaque monkeys) - can also infect humans Properties of Herpesvirus Spherical virion, icosahedral capsid dsDNA, linear more than 35 proteins in virion
*proteins encode enzymes used by virus during production of genes and glycoprotein envelope

Primary infection Transmitted by contact- virus enters mucosal surfaces or broken skin HSV-1 = latent infection in the trigeminal ganglia HSV-2 = latency in sacral ganglia
*intact skin- resistant

Latent infection Viral persistence in latency lasts for lifetime of the host Reactivation occurs in: axonal injury, fever, physical or emotional stress and exposure to UV light >80% of population harbor HSV 1 in latent form
*reactivation will occur only in small proportion of population for unknown reasons

enveloped- contains viral glycoproteins, Fc receptors *Fc receptor- evade immunity replicates within the nucleus, buds from the nuclear membrane *nuclear membrane becomes the envelope of the virus
Review: All DNA replicates in the nucleus except pox virus All RNA replicates in the cytoplasm except orthomyxo and retroviridae

Clinical findings: HSV-1: 1. Oropharyngeal & eye disease IP: 3-5 days *not all will be symptomatic Gingivostomatitis Ugahip Pharyngotonsilitis Keratoconjunctivitis Recurrent infection: cold sores, or fever blisters, keratitis

Outstanding characteristics: encode many enzymes establish latent infections (site- vary depending on type) persist indefinitely in infected hosts frequently reactivated in immunosuppressed hosts some are cancer-causing (EBV)

2.

Gingivostomatitis Skin infection Herpetic whitlow-seen on fingers; especially affecting denstist

162 capsomeres each capsomere has vertices which contains the glycoprotein spikes responsible for attachment to the host

3. 4.

Herpes gladiatorum or mat herpes- seen on bodies of wrestlers Eczema herpeticum- in person with chronic eczema- may be fatal Encephalitis Most common in HSV 1 Genital herpes Usually caused by HSV-2 Primary infections: severe, lasting about 3 weeks Vesiculoulcerative lesions: painful and may be associated with fever, malaise, dysuria, (+) inguinal LAD
Systemic sx + LAD +painful lesion *H. ducreyi= no systemic sx

Herpes simplex viruses Infect epithelial cells & establish latent infections in neurons (dorsal root ganglia) 2 types: 1. HSV 1- diseases above the waist -spread by contact (involving infected saliva) -oropharynx 2. HSV 2- below the waist -transmitted sexually or from maternal genital infection to a newborn
*both can cause encephalitis but more of HSV 1

Cross reactivity with HSV-1= less severe infection Neonatal herpes MOT: contact with herpetic lesions in the birth canal May be acquired postnatally Prevention: delivery by cesarean section Clinical Mx: lesions (vesicular) of the skin, eye, mouth; encephalitis (almost always fatal; cause permanent neurologic deficit) ; disseminated disease Treatment: Acyclovir- standard therapy Valacyclovir, vidarabine -inhibitors of viral DNA synthesis 5.

Cytomegalovirus Disease: Cytomegalic Inclusion Disease Generalized infection of infants caused by intrauterine or early postnatal infection with CMV May lead to severe congenital anomalies MOT: close person-person contact Virus may be shed in urine, saliva, semen, breast milk, and cervical secretions; and in circulating WBCs
*site of latency: kidneys, glands, lymphoid organs

IP: 4-8 weeks in older children and adults Systemic infection: lung, liver, esophagus, colon, kidneys, monocytes and T and B lymphocytes Involvement of salivary gland- common

Burkitt s lymphoma Tumor of the jaw in African children and young adults

Individuals at great risk for CMV: 1. Those receiving organ transplants 2. Those with malignant tumors receiving chemotherapy 3. Those with AIDS Most common complication- pneumonia CMV Congenital and Perinatal Infection Cytomegalic Inclusion disease of the newborn Involvement of the CNS and RES CM: IUGR (intrauterine growth retardation), jaundice, hepatosplenomegaly, thrombocytopenia, microencephaly, retinitis Survivors will have severe hearing loss, ocular abnormalities (blindness) and mental retardation Laboratory Diagnosis Polymerase chain reaction assays- for routine detection of CMV infection Serology- to detect antibodies against CMV Treatment DOC: Ganciclovir Foscarnet- used to treat cytomegalic retinitis *CMV vaccines are under development Epstein-Barr Virus Disease: Acute infectious mononucleosis Associated with nasopharyngeal carcinoma, Burkitt s lymphoma, Hodgkins lymphoma, gastric CA Target cell: B lymphocytes (CD21 or CR2 receptors) Can replicate in the epithelial cells of the oropharynx, parotid gland, and uterine cervix
Kissings disease

Nasopharyngeal carcinoma Common in males of Chinese origin

MOT: by infected saliva- initiates infection in the oropharynx Infected B cells- produces autoantibodies- heterophil antibodiesreacts with antigens on sheep erythrocytes (agglutination)
EBV heterophil (+) CMV- heterophil (-)

Laboratory Diagnosis Nucleic acid hybrization Most sensitive means of detecting EBV Serology: To detect EBV antibodies ELISA tests, immunoblot assays, indirect immunofluorescence test using EBV-postive lymphoid cells Heterophil agglutination test Agglutinates sheep RBCs Treatment: Acyclovir- reduces EBV shedding from the oropharynx but does not affect the number of EBV-immortalized B cells *no vaccine available Human Herpesvirus 6 1986 T-lymphotropic human herpesvirus 6 First isolated from peripheral blood mononuclear cells from patients with lymphoproliferative disorders Receptor: human CD46 Grows well in CD4 T lymphocytes, B cells and cells of glial, fibroblastoid, and megakaryocyte origin

Immunosuppression reactivates EBV latent infections Infectious mononucleosis Primary EBV infection in adolescents and young adults IP: 30-50 days Headache, fever, malaise, fatigue and sore throat LAD, splenomegaly, hepatitis Oral hairy leukoplakia Wart-like growth on the tongue in some HIV-infected persons and transplant patients- epithelial focus of EBV replication

Cell latenly infected= not known Virus may be present in saliva Epidemiology:>90% of children 1>yo and adults are virus positive Disease: roseola infantum or sixth disease, exanthema subitum- 6 day
course of disease (3 days fever then (-) fever (+) maculopapular rash

Human Herpesvirus 7 T-lymphotropic Recovered from peripheral blood lymphocytes of health individual Persistent infections in the salivary glands Human herpesvirus 8 Aka Kaposi sarcoma-associated herpesvirus (KSHV) Genome contains numerous genes related to cellular regulatory genes involved in cell proliferation, apoptosis and host responses MOT: through contact with oral secretionsSexually (MSM) Vertically Blood Organ transplant KSHV may be found in breast milk Common in Africa Lab dx: Serology Treatment: Foscarnet, Ganiciclovir, cidofovir Zoster Unilateral vesicular eruption within a dermatome, often associated with severe pain.

Ramsay Hunt Syndrome 1. Pain and vesicles in the external auditory canal 2. Loss of sense of taste in the anterior 2/3 of the tongue 3. Ipsilateral facial palsy -The geniculate ganglion of the sensory branch of the facial nerve is involved. Immunity Previous infection with varicella = lifelong immunity Antibodies induced by varicella vaccine persist for at least 20 years Laboratory Diagnosis Treatment: Acyclovir, valacyclovir, famciclovir and Foscarnet Prevention: Live attenuated varicella vaccine VZIG

B virus Disease: acute ascending myelitis and encephalomyelitis propensity to cause

neurologic disorders

MOT: monkey-bite; through respiratory route ocular splash exposure Treatment: acyclovir- given immediately after exposure Varicella-Zoster Virus Diseases: 1. Varicella (chickenpox) -highly contagious disease -characterized by generalized vesicular eruptions of the skin and mucous membranes (exanthem and enanthem) -the acute disease 2. Zoster (shingles) -the reactivation of the varicella virus present in latent form in the neurons in sensory ganglia -sporadic, rash is limited to the skin innervated by a single sensory ganglion Clinical Manifectations: Varicella IP: 10-21 days (usually 14-17 days) Low-grade fver, malaise, rash= maculopapules to vesicles over hours to days (trunk-face-limbs-buccal- pharyngeal mucosa) Vesicles appear in crops (all stages maybe seen at the same time)