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ID 115516
タイトル別表記
Cynomolgus macaque TRIMCyp-resistant HIV-1
著者
Sultana, Tahmina Osaka University
Nakayama, Emi E. Osaka University
Tobita, Satoshi Osaka University
Yokoyama, Masaru National Institute of Infectious Diseases
Seki, Yohei Kyoto University
Saito, Akatsuki Kyoto University
Akari, Hirofumi Kyoto University
Sato, Hironori National Institute of Infectious Diseases
Shioda, Tatsuo Osaka University
資料タイプ
学術雑誌論文
抄録
Old World monkey TRIM5α strongly suppresses human immunodeficiency virus type 1 (HIV-1) replication. A fusion protein comprising cynomolgus macaque (CM) TRIM5 and cyclophilin A (CM TRIMCyp) also potently suppresses HIV-1 replication. However, CM TRIMCyp fails to suppress a mutant HIV-1 that encodes a mutant capsid protein containing a SIVmac239-derived loop between α-helices 4 and 5 (L4/5). There are seven amino acid differences between L4/5 of HIV-1 and SIVmac239. Here, we investigated the minimum numbers of amino acid substitutions that would allow HIV-1 to evade CM TRIMCyp-mediated suppression. We performed random PCR mutagenesis to construct a library of HIV-1 variants containing mutations in L4/5, and then we recovered replication-competent viruses from CD4+ MT4 cells that expressed high levels of CM TRIMCyp. CM TRIMCyp-resistant viruses were obtained after three rounds of selection in MT4 cells expressing CM TRIMCyp and these were found to contain four amino acid substitutions (H87R, A88G, P90D and P93A) in L4/5. We then confirmed that these substitutions were sufficient to confer CM TRIMCyp resistance to HIV-1. In a separate experiment using a similar method, we obtained novel CM TRIM5α-resistant HIV-1 strains after six rounds of selection and rescue. Analysis of these mutants revealed that V86A and G116E mutations in the capsid region conferred partial resistance to CM TRIM5α without substantial fitness cost when propagated in MT4 cells expressing CM TRIM5α. These results confirmed and further extended the previous notion that CM TRIMCyp and CM TRIM5α recognize the HIV-1 capsid in different manners.
掲載誌名
Journal of General Virology
ISSN
00221317
14652099
cat書誌ID
AA00698722
出版者
Microbiology Society
97
4
開始ページ
963
終了ページ
976
発行日
2016-04-01
権利情報
This is an Open Access article published by the Microbiology Society under the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/)
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系