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Published on: August 31, 2014
SDF-1 gene polymorphisms and syncytia induction in Brazilian HIV-1 infected individuals
Maria Angelica Ehara Watanabe1, Gabriela Gonçalves de Oliveira Cavassin, Maristela Delgado Orellana
1Department of Pathological Sciences, Londrina State University, Londrina, PR, Brazil. maewat@sercomtel.com.br
Insights
The SDF1-3'A gene variant, a factor in HIV-1 co-receptor CXCR4, was studied in HIV patients and blood donors. This variant was absent in HIV patients, suggesting a potential role in HIV susceptibility.
Area of Science:
- Genetics
- Virology
- Immunology
Background:
- Stromal-derived factor (SDF-1) is the primary ligand for CXCR4, a crucial co-receptor for T-cell tropic HIV-1 entry.
- A common polymorphism, SDF1-3'A, exists in the 3' untranslated region of the SDF-1 gene.
- This variant involves a G to A transition at position 801, altering an Msp I restriction site.
Purpose of the Study:
- To investigate the frequency of the SDF1-3'A polymorphism in HIV-1 infected patients and healthy blood donors.
- To determine if the SDF1-3'A genotype correlates with syncytium-inducing (SI) or non-syncytium-inducing (NSI) HIV-1 variants.
Main Methods:
- Genotyping of 62 HIV-1 patients and 60 blood donors using PCR-restriction fragment length polymorphism (RFLP) analysis for the SDF1-3'A variant.
- Assessment of syncytia formation via co-culture of MT-2 cells with peripheral blood mononuclear cells from HIV-1 patients.
Main Results:
- The SDF1-3'A/3'A genotype was found at a low frequency (5%) in blood donors but was completely absent in HIV-1 infected patients.
- The wild-type (wt/wt) genotype for SDF-1 was present in 68% of HIV-1 patients, including both SI and NSI groups.
- No statistically significant correlation was observed between SDF-1 alleles and the capacity of HIV-1 to induce syncytia.
Conclusions:
- The SDF1-3'A polymorphism may play a role in HIV-1 susceptibility, as evidenced by its absence in the studied HIV-1 patient cohort.
- The SDF-1 gene polymorphism does not appear to be associated with the syncytium-inducing phenotype of HIV-1.
Abstract:
Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a co-receptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3' A, was identified in an evolutionary conserved segment of the 3' untranslated region of the SDF-1 gene. Sequence analysis revealed a common variant at position 801, a G-->A transition referred to as SDF1-3' A. Because this variant eliminates the Msp I restriction site PCR-restriction fragment length polymorphism (RFLP) analysis was used for rapid detection of genotypes. We genotyped 62 HIV infected patients and 60 non-HIV blood donors by RFLP analysis. We also assessed syncytia formation through co-culture of MT-2 cells with peripheral blood mononuclear cells from HIV patients. Syncytium-inducing HIV-1 variants have been shown to be clinically significant in the pathogenesis of HIV-1 infection. In our study, we detected a low frequency of 3'A/3'A (5%) in the blood donors but this genotype was absent in all HIV patients. We found that 41 (68%) HIV patients including syncytia inducing (SI) and non-syncytia inducing (NSI) groups contained the wild type (wt/wt) genotype for SDF-1. Our data indicate that there is no correlation between SDF-1 alleles and syncytium inducing HIV.
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