Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo
Hirofumi Aso,
Shumpei Nagaoka,
Eiryo Kawakami,
Jumpei Ito,
Saiful Islam,
Benjy Jek Yang Tan,
Shinji Nakaoka,
Koichi Ashizaki,
Katsuyuki Shiroguchi,
Yutaka Suzuki,
Yorifumi Satou,
Yoshio Koyanagi,
Kei Sato
Affiliations
Hirofumi Aso
Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, 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
Shumpei Nagaoka
Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan
Eiryo Kawakami
RIKEN Medical Sciences Innovation Hub Program, Yokohama, Kanagawa 2300045, Japan; Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba 2608670, Japan
Jumpei Ito
Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan
Saiful Islam
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 8600811, Japan; Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan
Benjy Jek Yang Tan
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 8600811, Japan; Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan
Shinji Nakaoka
Faculty of Advanced Life Science, Hokkaido University, Sapporo, Hokkaido 0600810, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 3320012, Japan
Koichi Ashizaki
RIKEN Medical Sciences Innovation Hub Program, Yokohama, Kanagawa 2300045, Japan
Katsuyuki Shiroguchi
RIKEN Center for Biosystems Dynamics Research, Suita, Osaka 5650874, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 2300045, Japan
Yutaka Suzuki
Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 2778561, Japan
Yorifumi Satou
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 8600811, Japan; Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, 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 Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 3320012, Japan; Corresponding author
Summary: For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. To reveal multiple characteristics of HIV-1-producing cells in vivo, we use a hematopoietic-stem-cell-transplanted humanized mouse model infected with GFP-encoding replication-competent HIV-1. We perform multiomics experiments using recently developed technology to identify the features of HIV-1-infected cells. Genome-wide HIV-1 integration-site analysis reveals that productive HIV-1 infection tends to occur in cells with viral integration into transcriptionally active genomic regions. Bulk transcriptome analysis reveals that a high level of viral mRNA is transcribed in HIV-1-infected cells. Moreover, single-cell transcriptome analysis shows the heterogeneity of HIV-1-infected cells, including CXCL13high cells and a subpopulation with low expression of interferon-stimulated genes, which can contribute to efficient viral spread in vivo. Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure.