• gamma herpesvirus
• DNA virus, icosahedra capsid, lipid envelope
• envelop glycoproteins that:
  • mediate attachement
  • important for making vaccine
• latency in B lymphocytes
  • circular viral DNA as episome into nucleus
  • expression of specific viral proteins leads to cellular transformation
    • latent infection membrane proteins

• developing countries: childhood (oncogenic potential: Burkett's lymphoma)
• developed countries: adolescence, early adulthood
  • 90% of adults in US have serum Ab
• EBV excretion in oropharyngeal secretions
  • almost always in immunocompromised hosts
  • sometimes in healthy adults
• "close" personal contact

1. EBV multiplies in pharyngeal lymphoid tissue and possibly oropharyngeal epithelial cells
2. dissemination throughout the lymphoreticular system (ex: spleen, lymph nodes, liver)
3. EBV latency and reactivation leads to periodic asymptomatic shedding
4. EBV cause transformation of B lymphocytes
   • cytotoxic T lymphocytes or "atypical lymphocytes" directed against infected B cells can be seen on peripheral blood film

• asymptomatic
• infectious mononucleosis
• sore throat, fever, lymphadenopathy
• tonsillar enlargement with exudate
• palatal petechiae at junction of hard and soft palate
• cervical lymphadenopathy
• splenomegaly and hepatomegaly
  • splenic trauma may result in splenic rupture
• rash to ampicillin

• hemolytic anemia
• splenic rupture, usually after trauma
• neurologic disease

tx for complication is corticosteroids (but no effective tx for EBV)

• B cell lymphomas (remember, EBV infects B cells)
  • Hodgkin's lymphoma
  • Burkitt's lymphoma
  • CNS lymphoma
• lymphoproliferative syndromes
• nasopharyngeal carcinoma

• atypical lymphocytosis
  • large lymphocyte with basophilic vacuolated cytoplasm, lobulated eccentric nuclei
• thrombocytopenia common
• mild elevation in transaminases
• differential dx
  • CMV
  • HIV
  • toxoplasmosis

• monospot (heterophile Ab's)
  • latex agglutination of horse RBC's
  • positive in most cases of acute mononucleus
• specific Ab's (IgM- within first 2 months; IgG- last for years)
  • viral capsid Ag (VCA)- Ig's bind to this
  • early Ag (EA)
  • Epstein Barr nuclear Ag (EBNA)- found in latent infection
• EBV DNA PCR

• beta herpesvirus
• largest human virus: linear DNA, icosahedra capsid, lipid envelope
• causes increase size of infected cells (cytomegaly)
• encodes proteins that prevent MHC I molecules from reaching cell surface
  • downregulates cytotoxic CD8 response

• contact with body fluids: shed in
  • saliva
  • urine
  • semen
• many adults seropositive
• sexual contact
• contaminated blood products
• perinatal- intrapartum, at delivery, via breast milk
• day care settins

• asymptomatic
• mononucleosis
• congenital CMV

• retinitis
• pneumonitis
• GI: colitis, esophagitis
• CNS: encephalitis, myelitis

• primarily in patients with HIV infection
• necrotizing chorioretinitis: peripheral or central (half is bilateral)
• irregular sheathing of bv's
• later development of scattered white granular lesions with hemorrhage
• several antiviral have been used for tx (ganciclovir, foscarnet, cidofovir)

• several manifestations involving multiple organ systems
  • jaundice
  • hepatosplenomegaly
  • petechial rash
  • microcephaly
  • low birth rate
  • developmental delay
  • motor disability
  • chorioretinitis
  • cerebral calcifications
• intrapartum transmission
  • primary infection during pregnancy
  • rarely, infection prior to pregnancy

• tissue: cytoplasmic and nuclear inclusions ("owl's eye" inclusion)
  • aggregates of CMV nucleoprotein cores
• serology: IgM/IgG (usually heterophilic negative)
• culture
  • shell vial technology
  • assay supernatant for early Ag, more rapid detection
• CMV DNA PCR

• beta herpesvirus (some homology with CMV and HHV7)
• can infect multiple cell types
  • T cells
  • B cells
  • NK cells
  • epitheial cells
  • macrophages
  • glial cells
• detect Ab in 70% of infants 12 months old and 90% in 24 months
• 80% of blood donors are seropositive

• mainly in kids
• usually in spring/fall
• spread by contacts with saliva

• roseola infantum (exanthem subitum: 6th disease) in some cases
• usually benign illness of children

• incubation period: 10 days
• abrupt onset high fever with well appearance, suboccipital adenopathy, red throat
• abrupt disappearance of fever with onset of macular rash
• drop in WBC prior to rash (may have atypical lymphocytes)
• duration: 6 days
• mononucleosis like illness in adults

• complication
  • usually self limited, mild
  • febrile seizures, rare encephalitis
• dx: serologic testing (IgG/IgM)
• tx: usually not indicated unless immunocompromised (mostly investigational)

• gamma herpesvirus
  • indistinguishable from other herpesviruses on EM
• also called Kaposi's sarcoma associated herpesvirus (KSHV)
• attach to heparan sulfate, integrin alpha 3 and beta 1
• target tissues
  • endothelial or spindle cells (Kaposi's sarcoma)
  • B lymphocytes: lymphomas
• latency: lymphocytes, endothelial cells

• transmission likely via sexual contact
• associated with malignancy
  • Kaposi's sarcoma
    • vascular tumors usually associated with HIV
    • 90% of KS lesions positive for HHV8 DNA or proteins by in situ hybridization
    • seen in HIV associated KS, African variety, those associated with transplantation
  • Castleman's disease- focal or multicentric lymphoma