Donor variability in HIV binding to peripheral blood mononuclear cells

Joshua J Anzinger,Gene G Olinger,Gregory T Spear

doi:10.1186/1743-422x-5-95

Abstract

BackgroundHIV infection of cells varies greatly between individuals, with multiple steps in the replication cycle potentially contributing to the variability. Although entry and post-entry variability of HIV infection levels in cells has been demonstrated, variability in HIV binding has not been examined. In this study, we examined variability of HIV binding to peripheral blood mononuclear cells (PBMC) from different donors.ResultsHIV binding to PBMC varied up to 3.9-fold between individuals and was independent of CD4. Replication of HIV in donor PBMC required CD4 and paralleled virus binding trends of donor PBMC. To assess the stability of virus binding phenotypes over time, HIV was bound to donors with low- and high-binding phenotypes. The binding phenotypes were maintained when tested weekly over a 4-week period for 3 of 4 donors, while one high-binding donor decreased to lower binding on the 4th week. The low- and high-binding phenotypes were also preserved across different HIV strains. Experiments performed to determine if there was an association between HIV binding levels and specific cell subset levels within PBMC showed no correlation, suggesting that HIV binds to multiple cell subsets.ConclusionThese results show that differences exist in HIV binding to donor PBMC. Our data also show that HIV binding to donor PBMC is CD4-independent and can change over time, suggesting that virus binding variability is due to differences in the expression of changeable cell-surface host factors. Taken together, this study highlights the impact of cell-surface factors in HIV binding to, and infection of, PBMC which likely represents an important step in HIV infection in vivo.

Highlights

HIV infection of cells varies greatly between individuals, with multiple steps in the replication cycle potentially contributing to the variability
We previously showed that the initial attachment of HIV primary isolates to peripheral blood mononuclear cells (PBMC) is independent of CD4 and not attributable to host factors previously suggested to be involved in HIV attachment to cells [13,14,15]
We assessed the possibility of differences in HIV binding to donor PBMC using the R5 primary isolate HIVTH and freshly isolated PBMC from 19 different healthy donors

Summary

Introduction

HIV infection of cells varies greatly between individuals, with multiple steps in the replication cycle potentially contributing to the variability. Infection of cells by HIV requires a number of host cell factors [1] Differences in these factors can contribute to variability in infection levels between individuals. Previous studies show that HIV infection levels of cells differ between individuals, with up to a 1000-fold variability in replication for HIV laboratory-adapted strains [2,3] and up to a 40-fold variability for HIV primary isolates [4]. The level of HIV infectivity in cells has been attributed to multiple steps in the HIV replication cycle, including entry (page number not for citation purposes). Virology Journal 2008, 5:95 http://www.virologyj.com/content/5/1/95 and several post-entry events [5] These studies show that differences in host factors between individuals can impact the efficiency of HIV infection. We previously showed that the initial attachment of HIV primary isolates to PBMC is independent of CD4 and not attributable to host factors previously suggested to be involved in HIV attachment to cells [13,14,15]

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