Identification of a virion-associated B cell entry determinant for Kaposi’s sarcoma associated herpes virus.

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAID	VIROL-1

* FARE Award Winner

Authors

• S. J. Dollery
• R. J. Santiago-Crespo
• D. Chatterjee
• E. A. Berger

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an HIV-associated lymphotropic herpes virus that causes two life-threatening B-cell lymphoproliferative disorders: multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL). During KSHV infection of the host, B cell infection is critical. B cells are believed to be the reservoir of KSHV during lifelong infection and are the likely origin of reactivation, dissemination and disease. In spite of all the evidence for B cell tropism, KSHV infection of B cells has until recently been remarkably inefficient. Using the newly discovered KSHV susceptible MC116 B cells and tonsillar B cells, we show that KSHV glycoprotein K8.1A is critical for KSHV infection of B cells, but dispensable for fibroblast and endothelial cell infection. Using a recombinant knockout virus and a panel of monoclonal antibodies, we demonstrate that K8.1A has a mechanistic role in viral attachment to cell surface heparin-sulphate proteoglycans and is also needed in a post-attachment step. Since KSHV B cell tropism determinants are important for the biology and pathogenesis of KSHV, knowledge of this nature is integral for developing therapeutic interventions.

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