HIV-1 Infection: The Functional Importance of SDF1, CCR2 and CCR5 in Protection and Therapeutics

Abstract

IntroductionInfection of human immunodeficiency virus (HIV)-1, the causative agent of spectrum of disease known as acquired immuno deficiency syndrome (AIDS), is a global pandemics. The prevalence and pattern of HIV1 infection varies globally. Some countries are more affected from fatal consequences then the others and the infection prototype varies within the country itself [1]. Despite global awareness and implementation of prevention strategies, the infection of HIV1 has increased at alarming rates in different parts of the world [1]. Advancement in the field of immunology, virology and population genetics has enabled us to understand the complex biology of HIV1 infection. The prevalence of HIV1 infection and progression to AIDS depends both on virus and host genetic factors [1]. There is tropism in HIV1 infection. The M-tropic and T-tropic HIV1 mediates their infection to human CD4+ cells by viral coat proteins gp120 and gp41 respectively. For HIV1 infection the G protein coupled seven transmembrane C-C chemokines receptors CCR2, CCR5, CXCR4 of host are extremely critical [2]. The R5, X4 and R5X4 strain of HIV1 exploit host CCR5, CXCR4 and both CCR5 and CXCR4 receptor respectively for their entry to host cells. The expression status of these three host factors namely CCR2, CCR5 and CXCR4 ligand SDF1 (stromal cell derived factor 1) on CD4+ immune cells decides the prevalence, propagation of HIV1 infection. Individuals among different populations harbouring CCR2 (64I), CCR5 (Δ32) and stromal cells derived factor 1-3' A (SDF1-3' A) mutant allele are comparatively more protected against infection of M and T trophic strains of HIV1 [3]. The presence and distribution of mutant, minor and wild allele at CCR loci and their respective involvement in disease progression and resistance against infection are the key signature marks of host pathogen co-evolution. This review will discuss about distribution of CCR2 (64I), CCR5-Δ32 and SDF1-3' A, alleles in diverse populations and how much important these alleles are for their role against HIV1 infection. HIV1 infection, geographical distribution, resistance towards drugs and therapeutic has captured a massive attention of research in the field of molecular biology, epidemiology and population genetics. Lastly the review emphasizes the key question, how natural ligands (SDF1, RANTES, MIP1-α, and MIP1-β) and synthetic antagonists against CCR2, CCR5 and SDF1 can prevail protection both M and T trophic HIV1. AbstractThe acute or chronic infection of HIV1 resulting to AIDS pandemics is one of the major causes of morbidity and mortality worldwide. The infection, prevalence and propagation of HIV1 depend both on adaptive mutation in virus and host genetic factors. Virus infection to human CD4+ immune cells together is assisted and restricted by various host factors. Presence of mutations in CCR2, CCR5 and CXCR4 ligands SDF1 are associated to protection against HIV1 infection and restriction to AIDS progression. Globally, individuals in various populations harbouring CCR2 (64I), ...

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