title: Enfuvirtide binding domain is highly conserved in non-B HIV type 1 strains from Cameroon, West Central Africa.
abstract: Recently T-20 or enfuvirtide, the first drug of a new class of antiretrovirals targeting the entry stage of the virus life cycle, has been clinically approved. Enfuvirtide is a peptide derived from the HR2 region of the transmembrane glycoprotein from the HXB2 HIV-1 subtype B prototype strain that binds to the HR1 region. Drug resistance seems to occur in the HR1 region between amino acids 36 and 45. We examined to what extent this region is conserved in 184 non-B strains from Cameroon: 132 (71.7%) CRF02-AG, 14 (7.6%) subtype A, 11 (5.9%) F2, 9 (4.8%) subtype D, 8 (4.3%) subtype G, 4 (2.1%) CRF01-AE, 4 (2.1%) CRF11-cpx, and 2 (1.1%) CRF06-cpx. Among the 184 strains studied, no amino acid mutation was found in the highly conserved three amino acid motif at codons 36-38 (GIV) that are important determinants of viral susceptibility to enfuvirtide. Other common substitutions like Q40H and N42T were also absent. The N42S polymorphism was present in 148 (80.4%) strains. Analysis of the HR2 domain, from which the peptide is derived, indicated a much greater genetic variability as compared to HR1.
authors.affiliation: Laboratoire de Santé Hygiène Mobile, Yaoundé, Cameroon.
authors.forename: Avelin Fobang
authors.initials: AF
authors.lastname: Aghokeng
authors.forename: Léonard
authors.initials: L
authors.lastname: Ewane
authors.forename: Bih
authors.initials: B
authors.lastname: Awazi
authors.forename: Aubin
authors.initials: A
authors.lastname: Nanfack
authors.forename: Eric
authors.initials: E
authors.lastname: Delaporte
authors.forename: Léopold
authors.initials: L
authors.lastname: Zekeng
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000595:Amino Acid Sequence; D002163:Cameroon; D017124:Conserved Sequence; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide