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Short communication: HIV type 1 phenotype, tropism, and sequence patterns: association and preference
Xiao-Nan Dong1, Xi Chen, Yu Chen
1Laboratory of Immunology, Research Centre for Medical Science and Department of Biology, Tsinghua University, and Protein Science Laboratory of MOE, Beijing 100084, Peoples Republic of China.
AIDS Research and Human Retroviruses
|March 30, 2005
Summary
Syncytium-inducing (SI) HIV-1 phenotypes correlate with CXCR4 coreceptor use and distinct V3 loop sequence features. Non-SI (NSI) phenotypes show no such specific sequence or coreceptor preferences.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- HIV-1 envelope glycoprotein 120 (gp120) mediates viral entry by interacting with CD4 and coreceptors.
- Coreceptor usage (CCR5 or CXCR4) is a key determinant of HIV-1 tropism and disease progression.
- Sequence variations in gp120, particularly the V1V2 and V3 loops, are associated with differential biological phenotypes.
Purpose of the Study:
- To investigate the relationship between HIV-1 biological phenotypes (syncytium-inducing/non-syncytium-inducing) and sequence characteristics of the V1V2 and V3 regions of gp120.
- To determine the association between these phenotypes and coreceptor usage (CXCR4 vs. CCR5).
Main Methods:
- Analysis of HIV-1 sequence data from the Los Alamos National Laboratory database.
- Correlation of biological phenotypes (SI/NSI) with coreceptor usage (X4/R5).
- Examination of sequence patterns, including net charge and N-linked glycosylation sites, in the V1V2 and V3 loops.
Main Results:
- Syncytium-inducing (SI) phenotypes were strongly linked to CXCR4 (X4) coreceptor usage, but not CCR5 (R5) usage.
- X4 HIV-1 isolates exhibited significantly higher net charges and a loss of N-linked glycosylation sites in the V3 loop compared to R5 isolates.
- No significant differences in net charge or N-linked glycosylation were observed in the V1V2 region between SI and NSI or X4 and R5 isolates.
- No correlation was found between V1V2 loop length and virus tropism or biological phenotypes.
Conclusions:
- HIV-1 V3 loop sequence features, specifically higher net charge and loss of glycosylation, are associated with CXCR4 tropism and syncytium-inducing ability.
- The V1V2 region's sequence characteristics do not appear to be major determinants of these specific phenotypes or tropism.
- These findings enhance our understanding of HIV-1 evolution and pathogenesis, highlighting the V3 loop's critical role.