Human immunodeficiency virus type 1-associated CD40 ligand transactivates B lymphocytes and promotes infection of CD4+ T cells.
Abnormal activation of B lymphocytes is a feature commonly seen in human immunodeficiency virus type 1 (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 the 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 interleukin-6 production. Furthermore, such viral entities were found to induce B-cell homotypic adhesion. These effects were paralleled at the intracellular level by the nuclear translocation of the ubiquitous transcription factor NF-kappaB. 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 the incorporation of host-encoded CD40L in HIV-1 is likely to play a role in the B-cell abnormalities that are seen in infected individuals.
Martin
Geneviève
G
Research Center in Infectious Diseases, CHUL Research Center, Laval University, Quebec (QC), Canada G1V 4G2.
Roy
Jocelyn
J
Barat
Corinne
C
Ouellet
Michel
M
Gilbert
Caroline
C
Tremblay
Michel J
MJ
D021581:Active Transport, Cell Nucleus / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D023201:CD40 Ligand / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology*; D014771:Virion / Q000276:immunology
D007074:Immunoglobulin G; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; D015534:Trans-Activators; D051996:Transcription Factor RelA; D023201:CD40 Ligand