Two-step evolution of HIV-1 budding system leading to pandemic in the human population
Yoriyuki Konno,
Keiya Uriu,
Takayuki Chikata,
Toru Takada,
Jun-ichi Kurita,
Mahoko Takahashi Ueda,
Saiful Islam,
Benjy Jek Yang Tan,
Jumpei Ito,
Hirofumi Aso,
Ryuichi Kumata,
Carolyn Williamson,
Shingo Iwami,
Masafumi Takiguchi,
Yoshifumi Nishimura,
Eiji Morita,
Yorifumi Satou,
So Nakagawa,
Yoshio Koyanagi,
Kei Sato
Affiliations
Yoriyuki Konno
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan
Keiya Uriu
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan; Graduate School of Medicine, the University of Tokyo, Tokyo 1130033, Japan; Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Aomori 0368561, Japan
Takayuki Chikata
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8608556, Japan
Toru Takada
Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 8128581, Japan
Jun-ichi Kurita
Graduate School of Medical Life Science, Yokohama City University, Kanagawa 2300045, Japan
Mahoko Takahashi Ueda
Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa 2591193, Japan
Saiful Islam
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8608556, Japan
Benjy Jek Yang Tan
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8608556, Japan
Jumpei Ito
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan
Hirofumi Aso
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 6068501, Japan
Ryuichi Kumata
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan
Carolyn Williamson
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa
Shingo Iwami
Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 8128581, Japan; MIRAI, Japan Science and Technology Agency, Kawaguchi 3320012, Japan
Masafumi Takiguchi
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8608556, Japan
Yoshifumi Nishimura
Graduate School of Medical Life Science, Yokohama City University, Kanagawa 2300045, Japan
Eiji Morita
Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Aomori 0368561, Japan
Yorifumi Satou
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8608556, Japan
So Nakagawa
Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa 2591193, Japan
Yoshio Koyanagi
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 6068501, Japan
Kei Sato
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan; Graduate School of Medicine, the University of Tokyo, Tokyo 1130033, Japan; International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan; Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 2778561, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 3320012, Japan; Corresponding author
Summary: The pandemic HIV-1, HIV-1 group M, emerged from a single spillover event of its ancestral lentivirus from a chimpanzee. During human-to-human spread worldwide, HIV-1 diversified into multiple subtypes. Here, our interdisciplinary investigation mainly sheds light on the evolutionary scenario of the viral budding system of HIV-1 subtype C (HIV-1C), a most successfully spread subtype. Of the two amino acid motifs for HIV-1 budding, the P(T/S)AP and YPxL motifs, HIV-1C loses the YPxL motif. Our data imply that HIV-1C might lose this motif to evade immune pressure. Additionally, the P(T/S)AP motif is duplicated dependently of the level of HIV-1 spread in the human population, and >20% of HIV-1C harbored the duplicated P(T/S)AP motif. We further show that the duplication of the P(T/S)AP motif is caused by the expansion of the CTG triplet repeat. Altogether, our results suggest that HIV-1 has experienced a two-step evolution of the viral budding process during human-to-human spread worldwide.
