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Detection of Chimeric Cellular: HIV mRNAs Generated Through Aberrant Splicing in HIV-1 Latently Infected Resting CD4+ T Cells.
- Source :
- Frontiers in Cellular & Infection Microbiology; 4/28/2022, Vol. 12, p1-23, 23p
- Publication Year :
- 2022
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- HIV
CD4 antigen
T cells
LATENT infection
HUMAN genes
Subjects
Details
- Language :
- English
- ISSN :
- 22352988
- Volume :
- 12
- Database :
- Complementary Index
- Journal :
- Frontiers in Cellular & Infection Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 156622063
- Full Text :
- https://doi.org/10.3389/fcimb.2022.855290