Human immunodeficiency virus type 2 (HIV-2) env gene analysis: prediction of glycoprotein epitopes important for heterotypic neutralization and evidence for three genotype clusters within the HIV-2a subtype.
The env gene sequences of ten tissue-culture-adapted human immunodeficiency virus type 2 (HIV-2) isolates from West African patients were determined. Alignment and comparison of the gene sequences and putative translation products with database sequences revealed 11-29% diversity at the nucleotide level and 15-31% variation at the protein level. From analysis of glycoproteins of HIV-2 strains sensitive and resistant to neutralization by HIV-1 antisera, five regions were identified as putative targets for cross-neutralizing antibody. The HIV-2 equivalent of the HIV-1 V3 loop was not included in this number. However, three of the HIV-2 peptides aligned with regions identified as targets for broad neutralization of HIV-1 strains. These were the V2 and CD4-binding domains of gp120 and the Kennedy domain in gp41. Phylogenetic analysis of the env gene sequences, together with HIV-2 env gene sequences published in the Los Alamos database, support the identification of two distinct HIV-2 subtypes, HIV-2a and HIV-2b. The new sequences are located within the HIV-2a subtype and allow prediction of at least three genotypes, designated I-III. Some correlation of genotype with geographical origin of isolates was noted. Genotype I viruses originate from Guinea Bissau and group II viruses mainly originate from The Gambia. One isolate from Guinea Bissau, HIV-2CAM4, appears phylogenetically older than other viruses in the HIV-2a subtype. The possible implications of this in the light of epidemiological findings in Guinea Bissau are discussed.
Breuer
J
J
National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
Douglas
N W
NW
Goldman
N
N
Daniels
R S
RS
D000595:Amino Acid Sequence; D001483:Base Sequence; D000939:Epitopes; D015752:Genes, env; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015498:HIV-2 / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000235:genetics
D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007106:Immune Sera