Enfuvirtide binding domain is highly conserved in non-B HIV type 1 strains from Cameroon, West Central Africa.
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.
Aghokeng
Avelin Fobang
AF
Laboratoire de Santé Hygiène Mobile, Yaoundé, Cameroon.
Ewane
Léonard
L
Awazi
Bih
B
Nanfack
Aubin
A
Delaporte
Eric
E
Zekeng
Léopold
L
Peeters
Martine
M
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
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide