title: gp41 sequence variability in HIV type 1 non-B subtypes infected patients undergoing enfuvirtide pressure.
abstract: 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.
authors.affiliation: Spallanzani Institute for Infectious Diseases, Rome, Italy. darrigo@inmi.it
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Arrigo
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.forename: Caterina
authors.initials: C
authors.lastname: Gori
authors.forename: Stefania
authors.initials: S
authors.lastname: Montieri
authors.forename: Stefano
authors.initials: S
authors.lastname: Aquaro
authors.forename: Rita
authors.initials: R
authors.lastname: Bellagamba
authors.forename: Evangelo
authors.initials: E
authors.lastname: Boumis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Daniele
authors.initials: D
authors.lastname: Pizzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rezza
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
mesh_terms: 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
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide