Kaposi sarcoma-associated herpesvirus (KSHV): Molecular biology and oncogenesis

Abstract

Kaposi sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA herpesvirus belonging to the gammaherpesvirinae subfamily. KSHV has been associated with the development of three neoplastic diseases: Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). In this review, we discuss the three KSHV-associated malignancies, KSHV genome, latent and lytic aspects of the viral lifecycle, putative viral oncogenes, as well as therapeutic regimens used for the treatment of KS, PEL, and MCD.

Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein

“…The primers used to amplify the light chain Fv region were 5'4C3-VL14-linker (5'-TCA GGT GGT GGC GGA TCT GGA GGT GGC GGA AGC GAC ATT GTG ATG ACA CAG TCT-3') and 3'4C3-VL14-HindIII (5'-GGA AGC TTT CCG TTT GAT TTC CAG CTT GGT-3'). The PCR products encoding the V H and V L domains of mAb 4C3 connected by a 15 amino acid linker (Gly 4 Ser) 3 were generated by fusion PCR using the purified individual V H and V L PCR fragments through the primers 5'4C3-VH20 and 3'4C3-VL14-HindIII. The PCR product was cloned into pCR2.1 vector, double digested with EcoRV and HindIII and ligated to PE-toxin expression vector 37°C, 5% CO 2 .…”

“…The KSHV latency phase is associated with restricted gene expression involved in maintenance of the viral genome as a nuclear episome, cell proliferation, immune evasion and suppression of apoptosis; the lytic phase involves temporal expression of genes leading to virus replication and infectious virion release. 3 Since its initial identification in 1994 by representational differential analysis of AIDS-related Kaposi sarcoma (KS) tissues, 4 KSHV was subsequently implicated in two uncommon, typically human immunodeficiency virus (HIV)-associated, B-cell lymphoproliferative disorders-primary effusion lymphoma (PEL), 5 and the plasmablastic variant of multicentric Castleman disease (MCD). 6 Its etiological role in all three diseases is now…”

Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence?

“…KS is the most common cancer in untreated AIDS patients, but it is also known to occur during other states of immunosuppression such as during organ transplant (Mesri et al, 2010). For a comprehensive review of KSHV, see Speck & Ganem (2010), Wen & Damania (2010), and Barton et al (2011).…”

“…MHV-68 mLANA (murine latency-associated nuclear antigen) and KSHV LANA share mostly conserved functions, whereas a LANA homolog has not been identified for EBV. mLANA/LANA expression is required for establishment and maintenance of latent infection (see Figure 2) (Barton et al, 2011;Wen & Damania, 2010). KSHV LANA may also have other functions aside from latency maintenance, as its expression has been found in tumors from all three diseases known to be caused by KSHV: KS, MCD, and PEL Kellam et al, 1999;Parravicini et al, 2000).…”

Measurement of γHV68 Infection in Mice

“…Unlike acute infection in which infectious virus can be directly assayed by the plaque-forming ability, latently-infected tissues/samples of γ-HVs do not usually contain detectable preformed infectious virus, instead, viral DNA is maintained as a circular episome with few genes expressed 6,7 . In this case, the viral latency load can be determined by the frequency of ex vivo reactivation of the virus from in vitro explants of latently-infected cells onto a permissive indicator cell culture (e.g.…”