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CD4-independent infection by HIV-2 is mediated by fusin/CXCR4
M J Endres1, P R Clapham, M Marsh
1Hematology-Oncology Division, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
Several members of the chemokine receptor family have been shown to function in association with CD4 to permit HIV-1 entry and infection. However, the mechanism by which these molecules serve as CD4-associated cofactors is unclear. In the present report, we show that one member of this family, termed Fusin/ CXCR4, is able to function as an alternative receptor for some isolates of HIV-2 in the absence of CD4. This conclusion is supported by the finding that (1) CD4-independent infection by these viruses is inhibited by an anti-Fusin monoclonal antibody, (2) Fusin expression renders human and nonhuman CD4-negative cell lines sensitive to HIV-2-induced syncytium induction and/or infection, and (3) Fusin is selectively down-regulated from the cell surface following HIV-2 infection. The finding that one chemokine receptor can function as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that differences in the affinity and/or the availability of this site can extend the host range of these viruses to include a number of CD4-negative cell types.
Insights
Fusin (CXCR4) acts as a primary receptor for some HIV-2 strains, enabling infection without CD4. This chemokine receptor discovery broadens understanding of viral entry mechanisms.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Chemokine receptors like Fusin (CXCR4) are known cofactors for HIV-1 entry, typically requiring CD4.
- The precise mechanism of chemokine receptors as CD4-associated cofactors for HIV entry remains unclear.
Purpose of the Study:
- To investigate the role of Fusin/CXCR4 as a potential alternative receptor for HIV-2 in the absence of CD4.
- To elucidate the mechanism of CD4-independent HIV-2 entry mediated by chemokine receptors.
Main Methods:
- Utilizing anti-Fusin monoclonal antibodies to inhibit CD4-independent viral infection.
- Assessing Fusin expression's ability to confer sensitivity to HIV-2 infection in CD4-negative cell lines.
- Monitoring Fusin receptor down-regulation on cell surfaces post-HIV-2 infection.
Main Results:
- CD4-independent HIV-2 infection was significantly inhibited by an anti-Fusin antibody.
- Transfection of CD4-negative human and nonhuman cell lines with Fusin rendered them susceptible to HIV-2 infection and syncytium induction.
- HIV-2 infection led to the selective down-regulation of Fusin from the cell surface.
Conclusions:
- Fusin/CXCR4 can function as a primary receptor for certain HIV-2 isolates, independent of CD4.
- The HIV envelope glycoprotein likely possesses a binding site for chemokine receptors, influencing viral host range.
- This finding suggests chemokine receptors are direct targets for viral entry, expanding the understanding of HIV tropism.
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