Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo.

Aso, Hirofumi; Nagaoka, Shumpei; Kawakami, Eiryo; Ito, Jumpei; Islam, Saiful; Tan, Benjy Jek Yang; Nakaoka, Shinji; Ashizaki, Koichi; Shiroguchi, Katsuyuki; Suzuki, Yutaka; Satou, Yorifumi; Koyanagi, Yoshio; Sato, Kei

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.