Cell-to-Cell Spread of HIV and Viral Pathogenesis
K M Law1, N Satija1, A M Esposito1
1Immunology Institute Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Insights
Human immunodeficiency virus type 1 (HIV-1) infection depletes CD4(+) T cells. Cell-to-cell interactions, like virological and infectious synapses, enhance HIV-1 spread and immune evasion.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) causes chronic infection, progressively depleting CD4(+) T lymphocytes, crucial for adaptive immunity.
- Cell-free HIV-1 is a prognostic indicator, but cell-to-cell transmission via interactions can significantly enhance viral spread.
- HIV-1 utilizes viral Env protein for cell adhesion and fusion, forming virological synapses that promote replication under immune and therapeutic pressure.
Purpose of the Study:
- To investigate the role of cell-cell interactions in HIV-1 infection dynamics.
- To understand how virological and infectious synapses contribute to viral spread and persistence.
- To elucidate the mechanisms by which HIV-1 evades immune responses through cell-mediated transmission.
Main Methods:
- Analysis of T cell interactions in lymphoid compartments and effector sites.
- Investigating the function of viral Env protein as a cell adhesion molecule.
- Characterizing virological and infectious synapses in HIV-1 infection.
Main Results:
- HIV-1-induced interactions between infected and uninfected T cells (virological synapses) enhance viral replication.
- Infectious synapses between antigen-presenting cells and T cells also promote viral spread.
- These cell-cell interactions facilitate HIV-1 persistence and immune evasion.
Conclusions:
- Cell-to-cell interactions are critical mechanisms for HIV-1 dissemination and persistence.
- Virological and infectious synapses contribute to viral spread, potentially overcoming therapeutic and immune pressures.
- Further research is needed to fully define the roles of these interactions throughout HIV-1 infection stages.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) gives rise to a chronic infection that progressively depletes CD4(+) T lymphocytes. CD4(+) T lymphocytes play a central coordinating role in adaptive cellular and humoral immune responses, and to do so they migrate and interact within lymphoid compartments and at effector sites to mount immune responses. While cell-free virus serves as an excellent prognostic indicator for patient survival, interactions of infected T cells or virus-scavenging immune cells with uninfected T cells can greatly enhance viral spread. HIV can induce interactions between infected and uninfected T cells that are triggered by cell surface expression of viral Env, which serves as a cell adhesion molecule that interacts with CD4 on the target cell, before it acts as the viral membrane fusion protein. These interactions are called virological synapses and promote replication in the face of selective pressure of humoral immune responses and antiretroviral therapy. Other infection-enhancing cell-cell interactions occur between virus-concentrating antigen-presenting cells and recipient T cells, called infectious synapses. The exact roles that these cell-cell interactions play in each stage of infection, from viral acquisition, systemic dissemination, to chronic persistence are still being determined. Infection-promoting immune cell interactions are likely to contribute to viral persistence and enhance the ability of HIV-1 to evade adaptive immune responses.
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