title: Conformational properties of the third variable loop of HIV-1AD8 envelope glycoprotein in the liganded conditions.
abstract: The conformational dynamics of the HIV-1 envelope glycoprotein gp120 and gp41 (Env) remains poorly understood. Here we examined how the V3 loop conformation is regulated in the liganded state using a panel of recombinant HIV-1NL4-3 clones bearing HIV-1AD8 Env by two experimental approaches, one adopting a monoclonal neutralizing antibody KD-247 (suvizumab) that recognizes the tip of the V3 loop, and the other assessing the function of the V3 loop. A significant positive correlation of the Env-KD-247 binding was detected between the liganded and unliganded conditions. Namely, the mutation D163G located in the V2 loop, which enhances viral susceptibility to KD-247 by 59.4-fold, had little effect on the sCD4-induced increment of the virus-KD-247 binding. By contrast, a virus with the S370N mutation in the C3 region increased the virus-KD-247 binding by 91.4-fold, although it did not influence the KD-247-mediated neutralization. Co-receptor usage and the susceptibility to CCR5 inhibitor Maraviroc were unaffected by D163G and S370N mutations. Collectively, these data suggest that the conformation of the liganded V3-loop of HIV-1AD8 Env is still under regulation of other Env domains aside from the V3 loop, including V2 and C3. Our results give an insight into the structural properties of HIV-1 Env and viral resistance to entry inhibitors by non-V3 loop mutations.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku, Tokyo, 162-0053, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku, Tokyo, 162-0053, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Takizawa
authors.affiliation: Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Miyauchi
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku, Tokyo, 162-0053, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Urano
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku, Tokyo, 162-0053, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute, 1314-1 Kawabe Kyokushi, Kikuchi, Kumamoto, 869-1298, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Murakami
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku, Tokyo, 162-0053, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Murakami
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku, Tokyo, 162-0053, Japan; Department of Clinical Laboratory, Nagoya Medical Center, 1-1 4-Chome, Sannomaru, Naka-ku, Nagoya, 460-0001, Japan. Electronic address: Komano@nnh.hosp.go.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017354:Point Mutation; D011487:Protein Conformation; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: Envelope structure; HIV-1; KD-247; Liganded condition; Neutralization; Suvizumab