Gene activity in primary T cells infected with HIV 89.6: intron retention and induction of genomic repeats

Retrovirology

Frederic D. Bushman¹  Karen E. Ocwieja²  Scott Sherrill-Mix¹ 

[1] Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, 425 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia 19104, PA, USA;Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia 19104, PA, USA

关键词: Retrotransposons;    HERV;    Chimera;    Expression;    Splicing;    Transcription;    RNA-Seq;    T cell;    HIV;   

Others  :  1226241
DOI  :  10.1186/s12977-015-0205-1

 received in 2015-04-24, accepted in 2015-08-28,  发布年份 2015

【 摘 要 】

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 _89.6infection 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 _89.6RNA 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 _89.6from 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 _89.6isolate disclosed multiple novel features of HIV-host interactions, notably intron retention and induction of transcription of retrotransposons and endogenous retroviruses.

【 授权许可】

   
2015 Sherrill-Mix et al.

【 图 表 】

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