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Infection of cells expressing CXCR4 mutants lacking N-glycosylation at the N-terminal extracellular domain is enhanced for R5X4-dualtropic human immunodeficiency virus type-1.
- Source :
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BMC infectious diseases [BMC Infect Dis] 2002 Dec 19; Vol. 2, pp. 31. Date of Electronic Publication: 2002 Dec 19. - Publication Year :
- 2002
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Abstract
- Background: Infection with human immunodeficiency virus type-1 (HIV-1) requires binding of the viral envelope gp120 to CD4 and to the CXCR4 coreceptor. Both, gp120 and CXCR4 are subject to N-glycosylation. Here we investigated the influence of the N-linked glycans g1 and g2 present on CXCR4 for HIV-1 infection.<br />Methods: The two CXCR4 N-glycosylation sites g1 (NYT) and g2 (NVS) were mutated by changing the first or third amino acids N or T/S to Q and A respectively (g1; N11Q or T13A; g2, N176Q or S178A). Human osteosarcoma cells (GHOST) expressing human CD4 and the various CXCR4 glycosylation mutants were tested for infection using NL4-3-based viruses with X4, R5 or R5X4-tropism differing only in the V3 loop region.<br />Results: All constructed cell lines expressing the various CXCR4 glycomutants showed similar permissiveness for the X4-monotropic virus and no change in the coreceptor specificity that allows infection of a CCR5-dependent R5-monotropic virus. Interestingly, the removal of glycan g1 significantly enhanced the permissiveness of GHOST cells for the R5X4 dualtropic virus. GHOST cells expressing the CXCR4-g1 or CXCR4-g1/2 mutants were infected at higher rates by the R5X4-dualtropic virus compared to cells expressing CXCR4-wt or CXCR4-g2 coreceptors.<br />Conclusion: Our present observations underscore a role for glycans present on the CXCR4 coreceptor in the entry process of HIV-1. The data will help to better understand the multifaceted mechanism of HIV infection and the selective forces which drive HIV-1 evolution from mono- to dual-tropism.
Details
- Language :
- English
- ISSN :
- 1471-2334
- Volume :
- 2
- Database :
- MEDLINE
- Journal :
- BMC infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 12489987
- Full Text :
- https://doi.org/10.1186/1471-2334-2-31