In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6

Kenta Matsuda; Katsuhisa Inaba; Yoshinori Fukazawa; Megumi Matsuyama; Kentaro Ibuki; Mariko Horiike; Naoki Saito; Masanori Hayami; Tatsuhiko Igarashi; Tomoyuki Miura

doi:10.1016/j.virol.2010.01.008

In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6

Kenta Matsuda, Katsuhisa Inaba, Yoshinori Fukazawa, Megumi Matsuyama, Kentaro Ibuki, Mariko Horiike, Naoki Saito, Masanori Hayami, Tatsuhiko Igarashi, Tomoyuki Miura

Vaccine and Gene Therapy Institute

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Pages (from-to)	134-143
Number of pages	10
Journal	Virology
Volume	399
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2010.01.008
State	Published - Mar 30 2010

Keywords

AIDS
CCR5 tropic
Mutagenesis
SHIV
V3 region

ASJC Scopus subject areas

Virology

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In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6. / Matsuda, Kenta; Inaba, Katsuhisa; Fukazawa, Yoshinori; Matsuyama, Megumi; Ibuki, Kentaro; Horiike, Mariko; Saito, Naoki; Hayami, Masanori; Igarashi, Tatsuhiko; Miura, Tomoyuki.

In: Virology, Vol. 399, No. 1, 30.03.2010, p. 134-143.

Research output: Contribution to journal › Article › peer-review

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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.",

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author = "Kenta Matsuda and Katsuhisa Inaba and Yoshinori Fukazawa and Megumi Matsuyama and Kentaro Ibuki and Mariko Horiike and Naoki Saito and Masanori Hayami and Tatsuhiko Igarashi and Tomoyuki Miura",

note = "Funding Information: We thank Dr. Julie Strizki, Schering Plough Research Institute, for providing AD101. This work was supported, in part, by Research on Human Immunodeficiency Virus/AIDS in Health and Labor Sci ences research grants from the Ministry of Health, Labor and Welfare, Japan, a grant-in-aid for scientific research from the Ministry of Education and Science, Japan, a research grant for health sciences focusing on drug innovation for AIDS from the Japan Health Sciences Foundation, and a grant from the Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) of Japan. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.",

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AU - Matsuyama, Megumi

AU - Ibuki, Kentaro

AU - Horiike, Mariko

AU - Saito, Naoki

AU - Hayami, Masanori

AU - Igarashi, Tatsuhiko

AU - Miura, Tomoyuki

N1 - Funding Information: We thank Dr. Julie Strizki, Schering Plough Research Institute, for providing AD101. This work was supported, in part, by Research on Human Immunodeficiency Virus/AIDS in Health and Labor Sci ences research grants from the Ministry of Health, Labor and Welfare, Japan, a grant-in-aid for scientific research from the Ministry of Education and Science, Japan, a research grant for health sciences focusing on drug innovation for AIDS from the Japan Health Sciences Foundation, and a grant from the Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) of Japan. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

PY - 2010/3/30

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N2 - 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.

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In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6

Abstract

Keywords

ASJC Scopus subject areas

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