title: In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6.
abstract: Although X4 tropic SHIVs have been studied extensively, they show distinct infection phenotypes from those of R5 tropic viruses, which play an important role in HIV-1 transmission and pathogenesis. To augment the variety of R5 tropic SHIVs, we generated a new R5 tropic SHIV from the highly pathogenic X4 tropic SHIV-KS661, a derivative of SHIV-89.6. Based on consensus amino acid alignment analyses of subtype B R5 tropic HIV-1, five amino acid substitutions in the third variable region successfully changed the secondary receptor preference from X4 to R5. Improvements in viral replication were observed in infected rhesus macaques after two passages, and reisolated virus was designated SHIV-MK38. SHIV-MK38 maintained R5 tropism through in vivo passages and showed robust replication in infected monkeys. Our study clearly demonstrates that a minimal number of amino acid substitutions in the V3 region can alter secondary receptor preference and increase the variety of R5 tropic SHIVs.
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inaba
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukazawa
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsuyama
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ibuki
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Horiike
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hayami
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: tmiura@virus.kyoto-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D008253:Macaca mulatta / Q000821:virology; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D016415:Sequence Alignment; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D013045:Species Specificity; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication / Q000502:physiology
chemical_list: D014764:Viral Proteins