title: Generation of a replication-competent simian-human immunodeficiency virus, the neutralization sensitivity of which can be enhanced in the presence of a small-molecule CD4 mimic.
abstract: Simian-human immunodeficiency virus (SHIV) carrying the envelope from the clade B clinical human immunodeficiency virus type 1 (HIV-1) isolate MNA, designated SHIV MNA, was generated through intracellular homologous recombination. SHIV MNA inherited biological properties from the parental HIV-1, including CCR5 co-receptor preference, resistance to neutralization by the anti-V3 loop mAb KD-247 and loss of resistance in the presence of the CD4-mimic small-molecule YYA-021. SHIV MNA showed productive replication in rhesus macaque PBMCs. Experimental infection of a rhesus macaque with SHIV MNA caused a transient but high titre of plasma viral RNA and a moderate antibody response. Immunoglobulin in the plasma at 24 weeks post-infection was capable of neutralizing SHIV MNA in the presence but not in the absence of YYA-021. SHIV MNA could serve a model for development of novel therapeutic interventions based on CD4-mimic-mediated conversion of envelope protein susceptible to antibody neutralization.
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Otsuki
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hishiki
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.affiliation: Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Hashimoto
authors.affiliation: Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Narumi
authors.affiliation: Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D018716:Molecular Mimicry / Q000276:immunology*; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000276:immunology / Q000502:physiology; D011995:Recombination, Genetic; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D012367:RNA, Viral; D019713:Receptors, CCR5