gp41 sequence variability in HIV type 1 non-B subtypes infected patients undergoing enfuvirtide pressure.
Enfuvirtide is the first of a new class of antiretroviral drugs that inhibits HIV entry. It is a 36 amino acid synthetic peptide that mimics the HR2 region of the HIV-1 gp41, preventing the fusion of viral and cellular membranes. Up to now, enfuvirtide was designed based on the HIV-1 B-subtype gp41, and resistance mutations to the fusion inhibitor have been investigated primarily in individuals infected with this subtype. To fill the gap, we analyzed the full length gp41 protein sequence of HIV-1 non-B strains from individuals receiving enfuvirtide-containing regimens. No primary resistance to the enfuvirtide binding domain (36-45 residues) was found. Resistance mutations were detected at follow-up visits and were comparable to those described among B-subtype HIV-1-infected patients; no sequence changes were detected in crucial HR1/HR2 gp41 sites such as the cytotoxic T lymphocyte epitope, cysteine loop, ectodomain, and 5-helix interaction and binding region.
D'Arrigo
Roberta
R
Spallanzani Institute for Infectious Diseases, Rome, Italy. darrigo@inmi.it
Ciccozzi
Massimo
M
Gori
Caterina
C
Montieri
Stefania
S
Aquaro
Stefano
S
Bellagamba
Rita
R
Boumis
Evangelo
E
Di Perri
Giovanni
G
Pizzi
Daniele
D
Antinori
Andrea
A
Rezza
Giovanni
G
Perno
Carlo Federico
CF
D000328:Adult; D000595:Amino Acid Sequence; D024882:Drug Resistance, Viral / Q000235:genetics; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry* / Q000145:classification / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010802:Phylogeny
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide