title: Functional characteristics of the natural polymorphisms of HIV-1 gp41 in HIV-1 isolates from enfuvirtide-naïve Korean patients.
abstract: HIV-1 gp41 plays a key role in viral entry. The insertion of Thr at position 4 and Met/Val/Phe substitutions at position 7 are frequently observed in the fusion peptide (FP) motif of gp41 without major enfuvirtide resistance associated with mutation in heptad repeats 1/2 (HR1/2) of HIV-1 isolates from Korean patients. Here, the influence of these mutations on their biological function was evaluated by employing HIV-1 variants with mutant FPs as shown previously and with recombinant HIV-1 using the env genes of 20 HIV-1 isolates from Korean patients. In an infectivity assay, all FP mutants showed lower infectivity than the wild-type NL4-3. In particular, the substitutions at position 7 led to much greater reductions in infectivity than the insertions at position 4. Nevertheless, the replication kinetics of most mutants were similar to those of the wild type, except that the FP mutants with an Ile insertion at position 4 and a Phe substitution at position 7 showed reduced replication. Moreover, most point mutants showed lower IC50 values for enfuvirtide than the wild type, whereas the L7M substitution resulted in a slightly increased IC50 value. The infectivity using the HIV-1 env recombinant viruses decreased in 14 cases but increased slightly in six cases compared with the wild type. Most recombinants were more susceptible to enfuvirtide than the wild type, except for three recombinants that showed slight resistance. Our findings may help to explain the potential mechanisms corresponding to the natural polymorphism of gp41 and to predict the efficiency of enfuvirtide in treatment of HIV-1-infected patients in Korea.
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-yeup, Cheongju, Chungbuk, 363-951, Republic of Korea.
authors.forename: YoungHyun
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-yeup, Cheongju, Chungbuk, 363-951, Republic of Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Yoon
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-yeup, Cheongju, Chungbuk, 363-951, Republic of Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-yeup, Cheongju, Chungbuk, 363-951, Republic of Korea.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Lim
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-yeup, Cheongju, Chungbuk, 363-951, Republic of Korea.
authors.forename: Byeong-Sun
authors.initials: BS
authors.lastname: Choi
authors.affiliation: Division of Respiratory Viruses, Korea National Institute of Health, Chungbuk, Republic of Korea.
authors.forename: Sung Soon
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-yeup, Cheongju, Chungbuk, 363-951, Republic of Korea. ckang@nih.go.kr.
authors.forename: Chun
authors.initials: C
authors.lastname: Kang
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D000077560:Enfuvirtide; D005260:Female; D015752:Genes, env; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009154:Mutation; D010446:Peptide Fragments / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide