A MODEL FOR ALIGNMENT OF ENV V1 AND V2 HYPERVARIABLE DOMAINS FROM HUMAN AND SIMIAN IMMUNODEFICIENCY VIRUSES

HIV-1 env gene encodes a multifunctional glycoprotein that is involved in virus infectivity, interactions between the virus and the host imm une system, and phenotypic characteristics of virus isolates in cultur e. A number of Env functions map by genetic analysis to V3, one of fiv e hypervariable domains that compose the surface component of Env gp12 0. V1 and V2 hypervariable domains of Env also contribute to the pheno type of HIV-1, although relationships between V1 and V2 genotypes and biological characteristics of HIV-1 are not well defined. One limitati on to genetic analysis of V1 and V2 is the extensive length variation that results from in-frame deletions or duplications of nucleotides an d renders alignments difficult among V1 and V2 sequences from differen t populations of viruses, We developed a model to facilitate rational alignments of V1 and V2 domains independent of their length, The align ment strategy constrains gap placement in V1 and V2 so that glycan mod ification motifs and potential alpha helices are intact, The alignment model accommodates the spectrum of HIV-1 subtypes, as well as HIV-2 a nd SIV V1 and V2 sequences, The model will facilitate genetic analysis and interpretation of amino acid changes in the hypervariable domains , For example, charged and uncharged amino acids are conserved in defi ned positions in each of the V1 and V2 hypervariable domains from a su bset of HIV-1 subtype B isolates, Biochemical characteristics of amino acids in V1 and V2 appear unrelated to cytotropic or syncytium-induci ng phenotypes of the viruses.