Abstract 280: Genetics and functions of Kaposi's sarcoma-associated herpesvirus (KSHV) glycoproteins in virion egress, infectivity and tumorigenesis

Abstract

Abstract Kaposi's sarcoma-associated herpes virus (KSHV), or human herpes virus 8, is a lymphotropic oncogenic virus that has been implicated in the pathogenesis of Kaposi's sarcoma; body cavity-based B-cell lymphoma (BCBL), or primary lymphoma; and some forms of Multicentric Castleman's disease. We have developed a conditional silencing system for partial inhibition of KSHV viral glycoprotein synthesized genes that are not susceptible to siRNA inhibition. We have successfully used this system to demonstrate that KHSV glycoprotein B (gB) is necessary for virion egress from BCBL-1 cells and virus infectivity (Subramanian, D'Auvergne, et al. J. Virol. 2008, 82:7144-54). To investigate the potential role of gB in tumorigenesis, BCBL-1 cells were transiently transfected with anti-gB siRNAs and codon optimized gB were mixed with matrigel and injected subcutaneously in nude mice. Direct measurement of tumors revealed that BCBL-1 cells transfected with anti-gB siRNAs produced tumors significantly smaller than mock-transfected BCBL-1 cells. Co-transfection of codon optimized gB appeared to abrogate the inhibition of tumor formation by siRNAs. These results show that gB is important for infectivity, virion egress and pleural effusion lymphoma (PEL) formation in mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 280. doi:1538-7445.AM2012-280