Sensitivity to a CD4 mimic of a consensus clone of monkey-adapted CCR5-tropic SHIV-MK38C

By acclimatizing CCR5-tropic tier 1B SHIV-MK1 to rhesus monkeys, a tier 2 SHIV-MK38 strain with neutralization resistance and high replication ability was generated. In this study, we generated SHIV-MK38C, a monkey-infectious consensus molecular clone of SHIV-MK38. Analysis using pseudotype viruses...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2023-01, Vol.578, p.171-179
Main Authors: Matsuura, Kanako, Yamaura, Mizuki, Sakawaki, Hiromi, Himeno, Ai, Pisil, Yalcin, Kobayakawa, Takuya, Tsuji, Kohei, Tamamura, Hirokazu, Matsushita, Shuzo, Miura, Tomoyuki
Format: Article
Language:English
Subjects:
AIDS
Animals
CCR5 tropic
CD4 mimic
Clone Cells
Consensus mutation
HIV
Monkey model
Neutralization resistance
SHIV
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus - genetics
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Summary:By acclimatizing CCR5-tropic tier 1B SHIV-MK1 to rhesus monkeys, a tier 2 SHIV-MK38 strain with neutralization resistance and high replication ability was generated. In this study, we generated SHIV-MK38C, a monkey-infectious consensus molecular clone of SHIV-MK38. Analysis using pseudotype viruses showed that MK38C was tier 1C because it lacked the N169D mutation, which is the most important mutation for neutralization resistance. MK38C harboring the N169D mutation became tier 2. However, the replication ability of SHIV-MK38C with N169D was low; more than 17 weeks elapsed before its detection in monkeys. Tier 1C MK38C was sensitive to a CD4 mimic. Therefore, SHIV-MK38C could be used to evaluate CD4 mimics in vivo. •We generated CCR5-tropic SHIV-MK38C, which had tier 1C neutralization ability.•SHIV-MK38C efficiently infected monkeys.•A mutation that induced neutralization resistance also reduced the replication ability of SHIV-MK38C.•Neutralization-resistant SHIV-MK38C was sensitive to a CD4 mimic.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2022.12.004