Host CCR5 and HIV-1 env/pol Polymorphisms: Role in transmission and virulence in the Kenyan population

Abstract

INTRODUCTION HIV-1 env protein and host cluster of differentiation antigen 4 (CD4) and wild-CC chemokine receptor 5 (CCR5) proteins are responsible for the attachment and entry of HIV-1 into T lymphocytes, hence influencing its infectivity. However, information on the flow, distribution, ARVs resistance patterns and co-infections of the HIV-1 sub-types is limited. An up-to-date comprehensive review on the role of CCR5/CD4 and env/pol protein polymorphisms in the susceptibility to HIV-1 infection, virulence, transmission, disease progression and discordance in the Kenyan population is lacking. This study aimed to review the role of CCR5/CD4 and HIV-1 env/pol protein polymorphisms in the transmission and virulence of HIV-1 in the Kenyan population. METHODOLOGY Data was sourced by literature search on Google Scholar, PubMed, and ScienceDirect. Grey literature articles were manually reviewed. Study selection was based on relevance to the role of CCR5/CD4 and env/pol protein polymorphisms in the transmission and virulence of HIV-1 were included in the review. Data were extracted from individual studies or articles. Data were synthesized regarding the information on the role of CCR5/CD4 and env/pol protein polymorphisms in the transmission and virulence of HIV-1 is synchronized under the headings; introduction, molecular characterization of HIV-1, HIV-1 treatment and antiretrovirals (ARVs) resistance, influence of host genes on HIV-1 disease progression, CD4 as HIV-1 receptors, and characterization of genetic/antigenic variants circulating in a given population. RESULTS A total of 74 articles were screened and 66 eligible articles were reviewed, four (4) of them touching on the origin and evolutionary mechanisms of the human immunodeficiency virus (HIV), while 21 articles addressed molecular characterization of the HIV-1. A total of 11 articles addressed HIV-1 treatment and ARVs resistance whereas 13 articles addressed the influence of host genes on HIV/AIDS disease progression. Eleven (11) and 8 articles addressed the CD4 as HIV-1 receptors and characterization of HIV-1 genetic/antigenic variants circulating in a given population, respectively. CONCLUSION There are many HIV-1 subtypes in circulation in Kenya with uneven distribution and it is difficult to accurately predict future metamorphosis and determine and monitor the flow and ARVs resistance patterns of the sub-types.A mutant allele of the β-chemokine receptor gene CCR5 prevents cell invasion and homozygotes for this mutation are resistant to infection with heterozygosity at this gene correlating with slowed HIV/AIDS disease progression. The C868T single nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition. RECOMMENDATIONS There is a need for accurate prediction of the future metamorphosis and regular evaluation and monitoring of the flow, distribution, ARVs resistance patterns and co-infections of the HIV-1 sub-types and their variation over time. Detailed assessment of the role of CCR5/CD4 and env/pol protein polymorphisms in the susceptibility to HIV-1 infection, virulence, disease progression and discordance in some couples in the Kenyan population is important.