Kaposi's sarcoma-associated herpesvirus (KSHV) is Gamma herpesvirus associated with a number of human malignancies which includes Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). Similar to other herpesviruses, KSHV is a large double stranded DNA virus which displays two alternate genetic life cycle programs upon infection of host cells (35)-In latent infection, gene expression is limited to a small subset of viral latent genes and includes the latency associated nuclear antigen (LANA) encoded by ORF73, viral cyclin (v-cyclin) encoded by ORF72, viral Fas-associated death domain (FADD) interleukin-1L-converting enzyme (FLICE) inhibitory protein (v-FLIP) encoded by ORF71, viral interferon (IFN) regulatory factors (vIRFs) encoded by K10 and Kaposin encoded by K12. During latency the viral episome is maintained through successive generations but no viral progeny are produced. In contrast, lytic replication leads to extensive viral gene expression, virion production, and death of the infected cell. Latently infected cells can be induced to enter the lytic cycle under specific physiological conditions. Thus, the pool of latently infected cells represents a reservoir of viral persistence from which infectious virus can be later reactivated with production of viral progeny which can spread to new target cells.
To date, it is widely accepted that latent infection by the virus plays a central role in viral pathogenesis with the expression of select genes responsible for targeting and controlling selective cellular pathways. Occasionally, lytic reactivation of the virus may be critical as expression of viral cytokine homologues during this phase may function as paracrine factors in stimulating cell growth and proliferation. The reduced gene expression pattern of latency minimizes the number of viral epitopes that are presented by infected cells to cytotoxic T lymphocytes (CTLs) and so contributes to the ability of the vims to escape immune surveillance and establishment of persistent infection (8, 9). In addition, a number of studies have shown that the genes expressed during latency play a major role in tumorigenesis of KSHV-associated cancers.
USPTO Backgrounds
USPTO Backgrounds