Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has been implicated in the development of Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL) and some forms of multicentric Castleman’s disease.
In 1994, Chang and Moore discovered new DNA fragments from KS lesion using representational difference analysis, which showed the presence of unique herpesviral sequence. This newly identified virus was called human gamma-herpesvirus 8 (γ-HHV8) or KSHV.
KSHV genome is a linear and double-stranded form and it has size range from 165 to 170Kb. Genome consist of two parts: long unique region (LUR), which contains all of the KSHV ORFs and is about 140kb in length, and terminal repeat (TR) sequences at both end of the linear viral genome. In the viral capsid, KSHV genome is a linear form, but upon infection the genome is circularized called episome.
Like other herpesviruses, KSHV also undergoes two modes of life cycles, latency and lytic cycle. KSHV genome is maintained as a circular form and only few genes are expressed during latent infection. Latent associated nuclear antigen (LANA), encoded by ORF 73, is one of the viral proteins expressed in latency. LANA is required for the replication and maintenance of viral genome. Other latently expressed proteins are vCyclin, vFLIP and vIRF3/LANA2. Upon lytic cycle, most genes are expressed, including structural proteins, enzymes for DNA synthesis, and virions are produced.
KSHV expresses many proteins which affect not only cellular signal transduction including MAPK, Wnt and Notch signaling but also cell cycle regulation, immune modulation and inhibition of programmed cell death. For example, vCyclin and LANA regulate cell cycle and K3, K5 and vIRFs regulate host immune system. Recently, it was demonstrated that KSHV has several micro RNAs which encoded in non-coding region of KSHV genome.