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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Expression cloning of new receptors used by simian and human immunodeficiency viruses
H K Deng1, D Unutmaz, V N KewalRamani
1Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Howard Hughes Medical Institute, New York University Medical Center, New York 10016, USA.
Abstract:
Several members of the chemokine-receptor family serve, in conjunction with CD4, as receptors for the entry of human immunodeficiency virus type I (HIV-1) into cells. The principal receptor for entry of macrophage-tropic (M-tropic) HIV-1 strains is CCR5, whereas that for T-cell-line-tropic (T-tropic) strains is CXCR4. Unlike HIV-1, infection with either M-tropic or T-tropic strains of simian immunodeficiency virus (SIV) can be mediated by CCR5, but not CXCR4. SIV strains will also infect CD4+ cells that lack CCR5, which suggests that these strains use as yet unidentified receptors. Here we use an expression-cloning strategy to identify SIV receptors and have isolated genes encoding two members of the seven-transmembrane G-protein-coupled receptor family that are used not only by SIVs, but also by strains of HIV-2 and M-tropic HIV-1. Both receptors are closely related to the chemokine-receptor family and are expressed in lymphoid tissues. One of the receptors is also expressed in colon and may therefore be important in viral transmission. Usage of these new receptors following experimental infection of non-human primates with SIV strains may provide important insight into viral transmission and the mechanisms of SIV- and HIV-induced acquired immune-deficiency syndrome.
Insights
Researchers identified new receptors used by simian immunodeficiency virus (SIV) and HIV-2 for cell entry. These findings advance understanding of viral transmission and acquired immune-deficiency syndrome (AIDS) mechanisms.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) uses CD4 and chemokine receptors (CCR5 for M-tropic, CXCR4 for T-tropic strains) for cell entry.
- Simian immunodeficiency virus (SIV) utilizes CCR5 but not CXCR4, and infects CD4+ cells lacking CCR5, indicating the existence of unknown receptors.
Purpose of the Study:
- To identify novel receptors utilized by SIV for cellular entry.
- To investigate the role of these receptors in viral tropism and transmission.
Main Methods:
- Expression-cloning strategy to identify SIV receptors.
- Gene isolation and characterization of seven-transmembrane G-protein-coupled receptors.
Main Results:
- Identified two novel G-protein-coupled receptors involved in SIV entry.
- These receptors are also used by HIV-2 and M-tropic HIV-1 strains.
- Receptors are expressed in lymphoid tissues; one is also found in the colon.
Conclusions:
- Discovered new cellular receptors crucial for SIV, HIV-2, and M-tropic HIV-1 entry.
- These findings offer insights into viral transmission routes, including potential colon involvement.
- Understanding these receptors may elucidate mechanisms of SIV and HIV-induced acquired immune-deficiency syndrome (AIDS).
