Detection of Chimeric Cellular: HIV mRNAs Generated Through Aberrant Splicing in HIV-1 Latently Infected Resting CD4+ T Cells.

Autor:	Lee MY; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Khoury G; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Olshansky M; Department of Microbiology, Biomedical Discovery Institute, Monash University, Melbourne, VIC, Australia., Sonza S; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Carter GP; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.; Doherty Applied Microbial Genomics, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., McMahon J; Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia., Stinear TP; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.; Doherty Applied Microbial Genomics, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Turner SJ; Department of Microbiology, Biomedical Discovery Institute, Monash University, Melbourne, VIC, Australia., Lewin SR; Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.; Victorian Infectious Diseases Service, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Purcell DFJ; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2022 Apr 28; Vol. 12, pp. 855290. Date of Electronic Publication: 2022 Apr 28 (Print Publication: 2022).
DOI:	10.3389/fcimb.2022.855290
Abstrakt:	Latent HIV-1 provirus in infected individuals on suppressive therapy does not always remain transcriptionally silent. Both HIV-1 LTR and human gene promoter derived transcriptional events can contribute HIV-1 sequences to the mRNA produced in the cell. In addition, chimeric cellular:HIV mRNA can arise through readthrough transcription and aberrant splicing. Using target enrichment coupled to the Illumina Mi-Seq and PacBio RS II platforms, we show that 3' LTR activation is frequent in latently infected cells from both the CCL19-induced primary cell model of HIV-1 latency as well as ex vivo samples. In both systems of latent HIV-1 infection, we detected several chimeric species that were generated via activation of a cryptic splice donor site in the 5' LTR of HIV-1. Aberrant splicing involving the major HIV-1 splice donor sites, SD1 and SD4 disrupts post-transcriptional processing of the gene in which HIV-1 is integrated. In the primary cell model of HIV-1 latency, Tat-encoding sequences are incorporated into the chimeric mRNA transcripts through the use of SD4. Our study unravels clues to the characteristics of HIV-1 integrants that promote formation of chimeric cellular:HIV mRNA and improves the understanding of the HIV-1 RNA footprint in latently infected cells. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lee, Khoury, Olshansky, Sonza, Carter, McMahon, Stinear, Turner, Lewin and Purcell.)
Databáze:	MEDLINE
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