HIV-1 co-receptor usage of contemporary transmitted/ founder viruses in Uganda

Abstract

Background: Globally, HIV remains a global public health threat despite the serious efforts to stop it using combination antiretroviral therapy. This could be attributed to the lack of preventative and curative treatment or vaccine to fend off the HIV-1 infection. Therefore, a comprehensive understanding of the molecular mechanisms of the HIV-1 transmission and evolution could provide an insight into the virus' vulnerabilities and its host defense mechanisms, including an accurate illustration of the transmitted or founder virus variants, the genetic and biological properties favoring HIV-1 mucosal transmission which would be very critical steps in developing a cure and vaccine for the HIV-1 infection. Several studies have investigated the properties employed by HIV-1 subtypes B and C, but these are not endemic in East Africa, and they may not represent the complete picture on the mucosal properties like co-receptors that favor the transmission of subtypes A, D, and their recombinant forms. This study investigated the HIV-1 co-receptor usage of the contemporary T/F virus strains circulating in Uganda and Kenya and their susceptibility to CCR5-antagonists. Methods: This study was nested within the “Exploration of the Virologic Characteristics of recently transmitted HIV-1 viruses in Uganda and Kenya” study that is investigating the biological properties of identified HIV-1 Transmitted Founder viruses of subtypes A, D and A/D. We retrieved 37 HIV-1 env clones from the parent study. The env clones were transformed, sequenced using Sanger sequencing platform and transfected. The viruses subtype diversity was predicted using REGA-HIV Subtyping tool. The virus tropism (co-receptors) and their susceptibility to CCR5-antagonist were predicted using Geno2Pheno V2.5. Results: We found 5 HIV-1 subtypes in Uganda, A1(45.5%), C (27.3%), D (13.6%) and A1C (4.5%), A1D (9.1%) of 22 samples and 2 subtypes in Kenya A1 (86.7%) and A1D (13.3%). Of the 37 samples tested, 24 (67.6%) were CCR5 tropism viruses and all were susceptible to CCR5-antagonists while 13 (32.4%) were CXCR4 tropism viruses and all were resistant to CCR5-antagonists. Conclusion: 54.5% and 86.7% of the HIV-1 T/F virus strains from Uganda and Kenya respectively were CCR5 tropism viruses and were susceptible to CCR5-antagonist. A1 HIV-1 subtype seems to be the dominating variant in Ugandan (45.5%) and Kenyan (86.7%) population and HIV-1 subtypes in Uganda seems to be more diversified (A1, C, D, A1C, and A1D) than in Kenya (A1 and A1D). There is need for in-vitro studies to be conducted to confirm these phenotypic properties and a bigger sample size would provide more representative findings.