Inhibition of HIV-1 infection on CD4+ T cells by blocking adhesion molecule mediated virus adsorption

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIAID	VIROL-7

Authors

• J.P. Kononchik
• P.D. Sun

Abstract

HIV-1 infection of primary T cells is well characterized with respect to CD4 and co-receptor recognition. The mechanism of entry involves interaction between these cell receptors and gp120, which is specific and required for infection. Virus adsorption to the cell surface, however, has been largely ignored. We have previously shown that viral envelope-associated sialic acids are important for HIV-1 adhesion to and infection of monocyte derived macrophages. It was shown that blocking host Siglec receptors significantly decreases surface bound gp120 and HIV-1 infection. Here, we present data examining the importance of gp120 glycosylation with respect to HIV-1 infection of primary T cells. Surface plasma resonance and ELISAs show that gp120 binds specifically to L-selectin, a host adhesion molecule present on naïve and central memory T cells. A novel Qdot-gp120 binding assay showed that gp120 bound to primary T cells expressing endogenous L-selectin, and anti-CD62L significantly blocked both gp120 binding to and HIV-1 infection of CD4 T cells. These data suggests an important role of L-selectin in facilitating HIV-1 infection. Combined with the previously published data regarding macrophages, we present a new paradigm in HIV-1 infection in which cellular lectin receptor-mediated viral adhesion precedes CD4 mediated viral entry.

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