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ID 115224
Miyakawa, Kei Yokohama City University
Matsunaga, Satoko Yokohama City University
Yokoyama, Masaru National Institute of Infectious Diseases
Kimura, Yayoi Yokohama City University
Nishi, Mayuko Yokohama City University
Kimura, Hirokazu Gunma Paz University
Sato, Hironori National Institute of Infectious Diseases
Hirano, Hisashi Yokohama City University
Tamura, Tomohiko Yokohama City University
Akari, Hirofumi Kyoto University
Miura, Tomoyuki Kyoto University
Sawasaki, Tatsuya Ehime University
Yamamoto, Naoki National Institute of Infectious Diseases|Tokyo Medical and Dental University
Ryo, Akihide Yokohama City University
Content Type
Journal Article
Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response.
Journal Title
Nature Communications
Springer Nature
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Medical Sciences