KSHV/HHV8-mediated hematologic diseases.

ABSTRACT The Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the causal agent of Kaposi sarcoma (KS), but is also pathogenetically related to several lymphoproliferative disorders, including primary effusion lymphoma (PEL)/extra-cavitary (EC)-PEL, KSHV-associated multicentric Castleman disease (MCD), KSHV-positive diffuse large cell lymphoma (DLBCL) and germinotropic lymphoproliferative disorder (GLPD). These different KSHV-associated diseases may co-occur and can have overlapping features. KSHV, similar to the Epstein-Barr virus (EBV), is a lymphotropic gamma herpesvirus which is preferentially present in abnormal lymphoid proliferations occurring in immune compromised individuals. Notably, both KSHV and EBV can infect and transform the same B cell, which is frequently seen in the KSHV-positive, EBV-positive PEL/EC-PELs. The mechanisms by which KSHV leads to lymphoproliferative disorders is thought to be related to the expression of a few transforming viral genes that can affect cellular proliferation and survival. There are critical differences between KSHV-MCD and PEL/EC-PEL, the two most common KSHV-associated lymphoid proliferations, including the viral associations, the patterns of viral gene expression and the cellular differentiation stage reflected by the phenotype and genotype of the infected abnormal B cells. Advances in treatment have improved outcomes, but mortality rates remain high. Our deepening understanding KSHV biology, the clinical features of KSHV-associated diseases, and newer clinical interventions should lead to improved and increasingly targeted therapeutic interventions.