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 | |
| State | Published - Mar 30 2010 |
| Externally published | Yes |
Fingerprint
Keywords
- AIDS
- CCR5 tropic
- Mutagenesis
- SHIV
- V3 region
ASJC Scopus subject areas
- Virology
Cite this
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
}
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
VL - 399
SP - 134
EP - 143
JO - Virology
JF - Virology
SN - 0042-6822
IS - 1
ER -