Human herpesvirus 8 (HHV-8) is classified as a γ2-herpesvirus and is related to Epstein-Barr virus (EBV), a γ1-herpesvirus. One important aspect of the γ-herpesviruses is their association with
neoplasia, either naturally or in animal model systems. HHV-8 is associated with B-cell-derived
primary effusion lymphoma (PEL) and
multicentric Castleman's disease (MCD), endothelial-derived
Kaposi's sarcoma (KS), and KSHV inflammatory
cytokine syndrome (KICS). EBV is also associated with a number of B-cell
malignancies, such as
Burkitt's lymphoma,
Hodgkin's lymphoma, and posttransplant lymphoproliferative disease, in addition to epithelial nasopharyngeal and gastric
carcinomas. Despite the similarities between these viruses and their associated
malignancies, the particular
protein functions and activities involved in key aspects of virus biology and neoplastic transformation appear to be quite distinct. Indeed, HHV-8 specifies a number of
proteins for which counterparts had not previously been identified in EBV, other herpesviruses, or even viruses in general, and these
proteins are believed to play vital functions in virus biology and to be involved centrally in viral pathogenesis. Additionally, a set of
microRNAs encoded by HHV-8 appears to modulate the expression of multiple host
proteins to provide conditions conductive to virus persistence within the host and possibly contributing to HHV-8-induced
neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.