HHV8 Flashcards
HHV8 structure & classification
Family: Herpesviridae
Genus: Rhadinovirus
Sub group: gammaherpesvirus
dsDNA
Baltimore: I
HHV8 receptor & tropism
Receptor: Cell surface Heparan sulfate
infect a variety of cells, including those of endothelial lineage, monocytes, and B cells.
Latent phase – In its latent phase, HHV-8 is maintained as a circular episome in the nucleus, which is tethered to the host chromosome, thus maintaining its replication during host cell division.
●Lytic phase – Activation of the virally encoded “lytic switch” gene, RTA, causes HHV-8 to enter its lytic phase, in which the full complement of viral-encoded genes is expressed and the host cellular machinery is redirected to the manufacture and assembly of progeny virions.
HHv8 clinical syndromes
- Children – In some immunocompetent children, primary HHV-8 infection may be associated with fever and a maculopapular rash.
- Kaposi sarcoma — Kaposi sarcoma (KS) is a multifocal angioproliferative tumor with four epidemiologic forms: Classic KS, endemic or African KS, AIDS-related KS, and organ transplant-associated
- Multicentric Castleman disease — HHV-8 is the etiologic agent of a plasmablastic form of MCD that is most common in the setting of HIV but can also arise in transplant recipients and in other patients without HIV [66]. HHV-8 associated MCD is a polyclonal B cell disorder characterized clinically by intermittent flares of inflammatory symptoms and signs, including fevers, night sweats, fatigue, and cachexia, and edema, together with lymphadenopathy and hepatosplenomegaly. Common laboratory abnormalities include anemia, thrombocytopenia, hypoalbuminemia, hyponatremia, and elevated inflammatory markers, most notably C-reactive protein (CRP)
- HHV-8 (Kaposi sarcoma) inflammatory cytokine syndrome (KICS) — HHV-8/Kaposi sarcoma inflammatory cytokine syndrome (KICS) is a syndrome characterized by severe inflammatory symptoms and elevated HHV-8 viremia [6,7]. The clinical manifestations are similar to those of MCD, and include fevers, night sweats, fatigue, and cachexia, and edema. Hepatosplenomegaly is common whereas lymphadenopathy is not [7]. Laboratory abnormalities include anemia, thrombocytopenia, hypoalbuminemia, hyponatremia, and elevated inflammatory markers including C-reactive protein
- Primary effusion lymphoma (PEL) — PEL is a rare variant of B-cell non-Hodgkin lymphoma (NHL) notable for its unusual presentation and aggressive clinical course [68,69]. The great majority of reported cases occur in people with HIV, although it may also be seen following solid organ transplantation, in older adults, and in chronic hepatitis C virus infection [70]. PEL usually presents as a lymphomatous effusion in serous body cavities, with pleural involvement seen in 60 to 90 percent of patients, followed by involvement of other body cavity membranes, including peritoneal (30 to 60 percent), pericardial (up to 30 percent), joint spaces, and rarely meninges
HHV8 therapeutics
MCD:
●Initial treatment with weekly rituximab for four weeks. Multiple additional four-week cycles may be necessary to achieve a response.
●Antiretroviral therapy is started or continued for all patients with HIV infection. For patients with poorly controlled HIV infection (eg, low CD4 count and/or higher HIV load), we also include antiviral therapy aimed at the HHV-8 (eg, ganciclovir) with the above combination regimen and as maintenance therapy.
HHV-8 replication is sensitive in vitro to ganciclovir, foscarnet, and cidofovir at achievable plasma concentrations
HHV8 screening when Donor sero positive
Latent & Lytic serology to be performed.
- D+/R+: risk of reactivation/reinfection.
Monitor DNA monthly for 1st 6 months. - D+/R-: antibodies AND DNA testing monthly for 1st 3 months.
Quarterly for months 3 to 12.
Types of KS
- Classic - usually indolent
- Endemic - aggressive & locally invasive
- Iatrogenic/graft related
- Epidemic - AIDS associated
