HIV-1 induces DCIR expression in CD4+ T cells.

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• The C-type lectin receptor DCIR is primarily found on antigen-presenting cells and acts as an attachment factor for HIV-1 in dendritic cells.
• Recent findings identified DCIR in CD4(+) T cells from rheumatoid arthritis patients, challenging its restricted expression.
• HIV-1 infection and rheumatoid arthritis share characteristics like chronic inflammation and immune hyperactivation.

Purpose of the Study:

• To investigate if HIV-1 infection promotes DCIR expression in CD4(+) T cells.
• To elucidate the mechanisms underlying HIV-1-induced DCIR up-regulation.
• To determine the functional consequences of increased DCIR expression on HIV-1 pathogenesis.

Main Methods:

• Analysis of DCIR expression in CD4(+) T cells from HIV-1 infected patients (both treated and untreated) and in vitro infected cells.
• Investigation of soluble factors mediating DCIR up-regulation on uninfected cells.
• Infection studies using HIV-1 with deleted Vpr or Nef genes.
• Assessment of DCIR's role in apoptosis pathways.
• Evaluation of DCIR's impact on HIV-1 attachment, entry, replication, and transfer.

Main Results:

• HIV-1 infection demonstrably drives DCIR expression in primary human CD4(+) T cells, irrespective of patient treatment status or acute in vitro infection.
• Soluble factors released by HIV-1-infected cells are responsible for up-regulating DCIR on bystander uninfected cells.
• Viral genes Vpr and Nef are not implicated in the induction of DCIR expression following acute HIV-1 infection.
• DCIR expression is associated with both caspase-dependent and -independent intrinsic apoptotic pathways.
• Elevated surface DCIR on CD4(+) T cells correlates with enhanced HIV-1 attachment, entry, replication, and cell-to-cell transfer.

Conclusions:

• HIV-1 actively induces DCIR expression on CD4(+) T cells, a novel finding with significant implications for viral pathogenesis.
• This HIV-1-mediated DCIR up-regulation may contribute to the dissemination of the virus within the host.
• The study highlights a potential new mechanism by which HIV-1 exploits host cell machinery to promote its lifecycle and spread.