Journal
CELL REPORTS
Volume 32, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107887
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Funding
- NIH/National Institute of Allergy and Infectious Diseases [NIAID] grant [5P30 AI028697]
- Agency for Medical Research and Development (AMED) [J-PRIDE 19fm0208006]
- AMED Research Program on HIV/AIDS [19fk0410014, 19fk0410019]
- AMED Emerging/Re-emerging Infectious Diseases [20fk0108146h0001]
- Japan Science and Technology Agency (JST) Core Research for Evolutional Science and Technology (CREST)
- Japan Society for the Promotion of Science (JSPS) KAKENHI [PAGS 16H06279]
- JSPS [18H02662, 16H06429, 16K21723, 17H05813, 19H04826, 20K15767, DC1 20J23299, DC1 19J22802, PD 19J01713]
- Joint Usage/Research Center program of inFront, Kyoto University
- Institute of Medical Science, University of Tokyo (IMSUT) Joint Research Project
- Takeda Science Foundation
- Lotte Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Daiichi Sankyo Foundation of Life Science
- Sumitomo Foundation
- Uehara Foundation
- Grants-in-Aid for Scientific Research [16H06429, 18H02662, 19H04826, 20K15767, 17H05813, 16K21723] Funding Source: KAKEN
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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 CXCL 13(high) 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.
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