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J. Virol. doi:10.1128/JVI.02542-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

HIV-1-associated CD40 ligand trans-activates B lymphocytes and promotes infection of CD4⁺ T

Research Center in Infectious Diseases, CHUL Research Center, and Faculty of Medicine, Laval University, Quebec, Canada

^* To whom correspondence should be addressed. Email: michel.j.tremblay{at}crchul.ulaval.ca.

	Abstract

Abnormal activation of B lymphocytes is a feature commonly seen in HIV-1-infected persons. However, the mechanism(s) responsible for this dysfunction is still poorly understood. Having recently shown that CD40L, the ligand for CD40, is inserted within emerging HIV-1 particles, we hypothesized that the contact between virus-anchored host CD40L and CD40 on the surface of B lymphocytes might result in activation of this cell type. We report here that CD40L-bearing viruses, but not isogenic virions lacking host-derived CD40L, can induce immunoglobulin G and IL-6 production. Furthermore, such viral entities were found to induce B-cell homotypic adhesion. These effects were paralleled at the intracellular level by nuclear translocation of the ubiquitous transcription factor NF-B. The presence of host-derived CD40L within virions resulted in an increased virus attachment to B cells and a more efficient B-cell mediated transfer of HIV-1 to autologous CD4⁺ T lymphocytes. All the above processes were independent of the virus-encoded envelope glycoproteins. Altogether the data gathered from this series of investigations suggest that incorporation of host-encoded CD40L in HIV-1 is likely to play a role in B-cell abnormalities that are seen in infected individuals.