This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, belongs in the gammaherpesvirinae subfamily and is believed to be the etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and a subset of multicentric Castleman's disease. KSHV, similar to the other viruses in the herpesvirus family, specifies numerous glycoproteins which are expressed during the virus lifecycle. Many of these KSHV glycoproteins have been shown to be important in virus entry, egress and virus-induced cell fusion. Glycoprotein M (gM) and gN are known to play important roles in multiple steps of herpesviruses, while their potential roles in KSHV infections are unknown. The central hypothesis of this project is that the KSHV gM and gN serve essential roles in two critical facets of the viral lifecycle: a) cytoplasmic virion morphogenesis and egress; b) virus-induced cell fusion. The overall experimental approach of the proposed investigations is to generate KSHV recombinant viruses deficient in either glycoprotein M (gM) or glycoprotein N (gN) genes utilizing the KSHV genome cloned into a bacterial artificial chromosome (BAC). These viruses will be utilized to address the functions of these two glycoproteins in virion morphogenesis and egress, and virus-induced cell fusion caused by a KSHV mutant virus having syncytial mutations in gB.
Specific Aim I : To construct and genetically characterize KSHV-BAC36 delta gM (gM-null) and BAC36 delta gN (gN-null) mutants utilizing the pGET-Rec recombination system in DH10B E.
coli Specific Aim II : To assess the role of KSHV gM and gN in cytoplasmic virion morphogenesis and egress, and virus-induced cell fus
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