Gene activity in primary T cells infected with $ HIV_{89.6} $: intron retention and induction of genomic repeats

Background HIV infection has been reported to alter cellular gene activity, but published studies have commonly assayed transformed cell lines and lab-adapted HIV strains, yielding inconsistent results. Here we carried out a deep RNA-Seq analysis of primary human T cells infected with the low passage HIV isolate $ HIV_{89.6} $. Results Seventeen percent of cellular genes showed altered activity 48 h after infection. In a meta-analysis including four other studies, our data differed from studies of HIV infection in cell lines but showed more parallels with infections of primary cells. We found a global trend toward retention of introns after infection, suggestive of a novel cellular response to infection. $ HIV_{89.6} $ infection was also associated with activation of several human endogenous retroviruses (HERVs) and retrotransposons, of interest as possible novel antigens that could serve as vaccine targets. The most highly activated group of HERVs was a subset of the ERV-9. Analysis showed that activation was associated with a particular variant of ERV-9 long terminal repeats that contains an indel near the U3-R border. These data also allowed quantification of >70 splice forms of the $ HIV_{89.6} $ RNA and specified the main types of chimeric $ HIV_{89.6} $-host RNAs. Comparison to over 100,000 integration site sequences from the same infected cell populations allowed quantification of authentic versus artifactual chimeric reads, showing that 5′ read-in, splicing out of $ HIV_{89.6} $ from the D4 donor and 3′ read-through were the most common $ HIV_{89.6} $-host cell chimeric RNA forms. Conclusions Analysis of RNA abundance after infection of primary T cells with the low passage $ HIV_{89.6} $ isolate disclosed multiple novel features of HIV-host interactions, notably intron retention and induction of transcription of retrotransposons and endogenous retroviruses..

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Retrovirology - 12(2015), 1 vom: 17. Sept.

Sprache:

Englisch

Beteiligte Personen:

Sherrill-Mix, Scott [VerfasserIn]
Ocwieja, Karen E. [VerfasserIn]
Bushman, Frederic D. [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

Chimera
Expression
HERV
HIV
RNA-Seq
Retrotransposons
Splicing
T cell
Transcription

Anmerkungen:

© Sherrill-Mix et al. 2015

doi:

10.1186/s12977-015-0205-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2099164215

Zugang & Verfügbarkeit




Zugehörige Publikationen/Bände

    Haven't found what you're looking for?