HERPESVIRUS GROUP

HSV, VZV, CMV, EBV, HHV-6

I.General characteristics: NA, envelope, capsid, replication

NA: linear, ds DNA

Enveloped:lipid, carbo, proteinderived from host nuclear membrane

Infectivity: eliminated by ether, lipid solvents

Replication

1.attachment, penetration, uncoating, move to nucleus

2.coding for nonstructural proteins: TK (HSV1/2; CMV) & DNA polymerase (all)

3.replication of viral DNA in nucleus

4.cytoplasmic synthesis of viral-specified proteins then transported to nucleus

5.Groups of HSV/CMV genes & fcns

alpha/immediate early - shut down host metab.

beta/early - enzymes for viral replicaton

gamma/late - structural proteins

6.Assembly underneath nuclear membrane, bud through to form envelope

7.Transport out via lysis or tubules

II. Definitions:persistent infection (chronic or latent w/reactivaton)

chronic: low level growth, no symptoms

latent: no growth, viral genome silent

reactivation: spontaneous or trigger to active or low level growth = disease or asymptomatic shedding

Latency sites:sensory neuron (HSV, VZV); B lymphocyte (EBV, HHV-6); Neutrophil (CMV-also salivary gland & renal tubular epithelium)

Immune response:Ab formed in primary helps in recovery not preventing reactivation; CMI impt in recovery from primary & recurrent

III.Malignancy

HSV-2: cervix (more often human papilloma virus)

EBV:Burkitt's lymphoma (Africans); Nasopharyngeal carcinoma (Chinese); B-cell lymphoma (immunosuppressed); lymphoma (primates)

IV.Pathogenesis:primary/recurrent, latency sites, reactivation

Herpes Simplex Virus 1/2 (HSV)

Primary:more severe w/ systemic component

Recurrent:same anatomic location, more localized, milder; reactivated latent or new

Latency:autonomic ganglia via peripheral nerves

Reactivation:travel down sensory nerve, replication in skin

Varicella Zoster Virus (VZV)

Primary:varicella (chickenpox), initial in respiratory tract, viremia to skin, rash

Latent:DRG, usu thoracic ganglia neural cells

Reactivaton:Herpes zoster (shingles), depressed CMI

Cytomegalovirus (CMV)

Transmission:transplacental, natal, postnatal, blood transfusions, day care, sexual

Either fetus/neonate/infant/todler or secually active

Asymptomatic shedding:m-y, saliva, sexual secrteions

Reactivation:immunocompromised

Lab:culture WBC/bronchoalveolar lavage fluid/urine (neonate only); Antibody testing for organ donors

Tx:ganciclovir (+ globulins w/ pneumonitis)

Prevention:CMV seronegative organ donors, ganciclovir prophylaxis

Epstein-Barr Virus (EBV)

Epidemiology

Incidence:social crowding, poor hygiene

Transmission:intimate contanct "kissing"

Pathogenesis/Immune response

Pathogenesis:replicate in pharynx, infect B lymphocytes, spread

Immune response:symptomatology, responds to VCA, EA, EBNA; mono-spot test, non-viral antigens

Lab:mono-spot (95% sensitive & specific but not in infants & young children); Anti-VCA w/ IgG (two serum specimens req.) & IgM (97% sen. & spec., also infants/kids); culture or PCR

Tx:supportive, antivirals reduce shedding, steroids for severe disease

Malignancy

Immunodeficient:EBV-associated B cell lymphomas, espec. w/cyclosporin A

Burkitt's lymphoma:children, jaw tumor, Africa & PNG, 98% Ab-titer or multiple gene copies

Nasopharyngeal carcinoma:South Chinese & eskimos, 100% of NPC cells

Human Herpesvirus Type 6 (HHV-6)

May have association w/ bone marrow transplant patients

V.Features:primary vs. recurrent, risk factors, major complications, asymptomatic shedding, lab diagnosis, antiviral therapy, vaccines

Oral herpes simplex:HSV-1, primary (gingivostomatitis) infants/toddlers, recurrent (herpes labialis, fever blister, cold sore), culture, acyclovir

Genital herpes simplex:HSV-2, primary & recurrent, culture, acyclovir

Ocular herpes simplex:HSV-1, primary (kerato-conjunctivitis), corneal scars, culture, trifluridine (topical) + steroids

Herpes encephalitis:HSV-1, most common sporadic life-threatening encephalitis, any age, 70% mortality if untreated, brain biopsy, soon (CSF PCR & probe) acyclovir

Neonatal herpes:75% HSV-2, virus from mother, complications w/ primary disease (early gestation-abortion; late gestation -premature; parturition - neonatal herpes), 70% mortality if untreated, IV acyclovir

Varicella (chickenpox):VZV, primary, school age children (winter/spring), rash, complications w/ spread to lung/liver/CNS, antigen detection, acyclovir

Herpes zoster (shingles):VZV, recurrent, elderly (nonseasonal) & immunosuppressed, posttherapeutic neuralgia, acyclovir

Congenital CMV:transplacental/natal/postnatal; 90% asymptomatic in neonatal, complications: hearing loss/behavioral/school learning; serious complications for intrauterine (10%): jaundice/petichiae/hepatosplenomegaly/30 % die/rest have neurological sequlae

CMV mononucleosis:usu. asymptomatic, cause mononucleosis syndrome

CMV in immunosuppressed:reactivation; risk: transplants/AIDS/leukemia/lymphoma/on chemo; complications: pneumonitis (80% fatal w/otreat)/chorioretinitis/colitis/hepatitis/fever

EBV infectious mononucleosis:(CIM) fever, mailaise, fatigue, sore throat, pharyngitis, cervical adenitis, splenomegaly, lymphocytosis (atypical), elevated liver enzymes (hepatitis rare); complications: severe disease, nasopharyngeal airway obstruction, CNS (aseptic meningitis, encephalitis)

HHV-6 roseola:Roseola Infantum, infants & toddlers, high fever w/o other symptoms.