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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)134-143
Number of pages10
JournalVirology
Volume399
Issue number1
DOIs
StatePublished - Mar 30 2010
Externally publishedYes

Fingerprint

Amino Acid Substitution
HIV-1
Viruses
Tropism
Macaca mulatta
Haplorhini
Phenotype
Amino Acids
Infection

Keywords

  • AIDS
  • CCR5 tropic
  • Mutagenesis
  • SHIV
  • V3 region

ASJC Scopus subject areas

  • Virology

Cite this

Matsuda, K., Inaba, K., Fukazawa, Y., Matsuyama, M., Ibuki, K., Horiike, M., ... Miura, T. (2010). In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6. Virology, 399(1), 134-143. https://doi.org/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. / 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 journalArticle

Matsuda, K, Inaba, K, Fukazawa, Y, Matsuyama, M, Ibuki, K, Horiike, M, Saito, N, Hayami, M, Igarashi, T & Miura, T 2010, 'In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6', Virology, vol. 399, no. 1, pp. 134-143. https://doi.org/10.1016/j.virol.2010.01.008
Matsuda, Kenta ; Inaba, Katsuhisa ; Fukazawa, Yoshinori ; Matsuyama, Megumi ; Ibuki, Kentaro ; Horiike, Mariko ; Saito, Naoki ; Hayami, Masanori ; Igarashi, Tatsuhiko ; Miura, Tomoyuki. / In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6. In: Virology. 2010 ; Vol. 399, No. 1. pp. 134-143.
@article{9467979a8e584c7ebea6db96dfff0593,
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.",
keywords = "AIDS, CCR5 tropic, Mutagenesis, SHIV, V3 region",
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",
year = "2010",
month = "3",
day = "30",
doi = "10.1016/j.virol.2010.01.008",
language = "English (US)",
volume = "399",
pages = "134--143",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6

AU - Matsuda, Kenta

AU - Inaba, Katsuhisa

AU - Fukazawa, Yoshinori

AU - Matsuyama, Megumi

AU - Ibuki, Kentaro

AU - Horiike, Mariko

AU - Saito, Naoki

AU - Hayami, Masanori

AU - Igarashi, Tatsuhiko

AU - Miura, Tomoyuki

PY - 2010/3/30

Y1 - 2010/3/30

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.

AB - 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.

KW - AIDS

KW - CCR5 tropic

KW - Mutagenesis

KW - SHIV

KW - V3 region

UR - http://www.scopus.com/inward/record.url?scp=77049095775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77049095775&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2010.01.008

DO - 10.1016/j.virol.2010.01.008

M3 - Article

C2 - 20102777

AN - SCOPUS:77049095775

VL - 399

SP - 134

EP - 143

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -