In:
Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-4-28)
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.
Type of Medium:
Online Resource
ISSN:
2235-2988
DOI:
10.3389/fcimb.2022.855290
DOI:
10.3389/fcimb.2022.855290.s001
DOI:
10.3389/fcimb.2022.855290.s002
DOI:
10.3389/fcimb.2022.855290.s003
DOI:
10.3389/fcimb.2022.855290.s004
DOI:
10.3389/fcimb.2022.855290.s005
DOI:
10.3389/fcimb.2022.855290.s006
DOI:
10.3389/fcimb.2022.855290.s007
DOI:
10.3389/fcimb.2022.855290.s008
DOI:
10.3389/fcimb.2022.855290.s009
DOI:
10.3389/fcimb.2022.855290.s010
DOI:
10.3389/fcimb.2022.855290.s011
DOI:
10.3389/fcimb.2022.855290.s012
DOI:
10.3389/fcimb.2022.855290.s013
DOI:
10.3389/fcimb.2022.855290.s014
DOI:
10.3389/fcimb.2022.855290.s015
DOI:
10.3389/fcimb.2022.855290.s016
DOI:
10.3389/fcimb.2022.855290.s017
DOI:
10.3389/fcimb.2022.855290.s018
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2619676-1
Permalink