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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
HIV-1 subtype C in vitro growth and coreceptor utilization
Thumbi Ndung'u1, Enoch Sepako, Mary Fran McLane
1Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education, Private Bag BO320, Bontleng, Gaborone, Botswana, Africa.
Insights
Human immunodeficiency virus type 1 subtype C (HIV-1C) predominantly uses R5 and dualtropic X4R5 coreceptors for entry in Botswana. This suggests HIV-1C does not evolve to a pure X4 phenotype, impacting treatment strategies.
Area of Science:
- Virology
- Immunology
- Epidemiology
Background:
- Human immunodeficiency virus type 1 subtype C (HIV-1C) is the most prevalent globally, causing approximately 50% of infections.
- Southern Africa bears a significant burden of HIV-1C, necessitating research into its unique biological characteristics.
- Understanding HIV-1C tropism is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the chemokine receptor usage of HIV-1C isolates from Botswana.
- To determine the predominant coreceptor tropism of HIV-1C in this region.
- To assess potential evolution of HIV-1C tropism over the course of infection.
Main Methods:
- Generation of HIV-1C virus isolates from infected individuals at various disease stages.
- Analysis of coreceptor tropism, specifically chemokine receptor usage (CCR5 and CXCR4).
- Phenotypic characterization of virus entry based on coreceptor utilization.
Main Results:
- The R5 tropism (CCR5-using) was predominant among the studied HIV-1C isolates.
- A smaller proportion of viruses exhibited dualtropic X4R5 (CCR5 and CXCR4-using) tropism.
- No viruses with pure X4 tropism (CXCR4-only using) were identified, indicating a lack of evolution towards this phenotype.
Conclusions:
- HIV-1C in Botswana primarily utilizes R5 and X4R5 coreceptors for entry.
- The absence of X4-only tropism suggests limited viral evolution towards this entry pathway in the aging epidemic.
- These findings have significant implications for the design and efficacy testing of antiretroviral therapies and prevention strategies.
Abstract:
Human immunodeficiency virus type 1 subtype C (HIV-1C) accounts for about 50% of all HIV infections in the pandemic and is the predominant subtype in the heavily burdened region of southern Africa. HIV-1C possesses unique genetic and phenotypic features that might be associated with biological differences compared to other subtypes. Here, we generated virus isolates from individuals at different stages of HIV-1C infection and investigated the chemokine receptor repertoire that the derived HIV-1C isolates may utilize for entry. Our results show that the R5 phenotype predominates among viruses in Botswana, with a lesser contribution of viruses showing the dualtropic X4R5 phenotype. No viruses of pure X4 phenotype were found, which suggests no discernable evolution of HIV-1C to a monotropic X4 phenotype as the epidemic ages in Botswana. Usage of other coreceptors was rare and apparently insignificant. These results enhance our understanding of HIV-1C biology, with implications for designing and testing therapeutic and prophylactic agents.
