Genomic Diversity of Human Immunodeficiency Viruses

Globally circulating strains of human immunodeficiency virus type one (HIV-1) exhibit an extraordinary degree of genetic diversity. Sequences derived from HIV-1 strains have historically been classified on the basis of their phylogenetic relationships. The viruses have been classified into groups, subtypes or clades and circulating recombinant forms (CRFs). Groups were originally named M for main, O for outlier and N for Non-M-Non-O. The identification of subtypes and CRFs provides a means of tracking the dissemination of the pandemic.

Various methods to study the molecular epidemiology of HIV-1 are virus isolation, cloning, DNA sequencing, restricted fragment length polymorphism of the molecularly cloned and amplified genome (PCR-RFLP), RNase mismatch cleavage analyses of RNA, RNA heteroduplexes derived from culture amplified virus, primer mismatch sensitive PCR to identify specific mutations, single strand conformational polymorphism (SSCP) to localize mutations arising over short regions of env gene, denaturing gradient gel electrophoresis and serological assays based on V3 peptide. Except for PCR-RFLP and denaturing gradient gel electrophoresis, these techniques do not easily allow simultaneous analyses of multiple sequence variants and include the laborious and selective process of virus co-cultivation or molecular cloning prior to analyses. The extensive DNA sequence analyses remain the gold standard for epidemiological investigations.

Both HIV-1 and HIV-2 are present in India. The Indian strains of HIV1 also show diverse subtypes with HIV1 subtype C predominance. Tracking the genetic diversity has implications towards understanding the evolution of the epidemic, immunopathogenesis, natural course of infection, response to therapy and most importantly vaccine design.