Back to Search
Start Over
HIV-1 Infection of Primary CD4 + T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements.
- Source :
-
Journal of virology [J Virol] 2017 Dec 14; Vol. 92 (1). Date of Electronic Publication: 2017 Dec 14 (Print Publication: 2018). - Publication Year :
- 2017
-
Abstract
- Endogenous retroviruses (ERVs) occupy extensive regions of the human genome. Although many of these retroviral elements have lost their ability to replicate, those whose insertion took place more recently, such as the HML-2 group of HERV-K elements, still retain intact open reading frames and the capacity to produce certain viral RNA and/or proteins. Transcription of these ERVs is, however, tightly regulated by dedicated epigenetic control mechanisms. Nonetheless, it has been reported that some pathological states, such as viral infections and certain cancers, coincide with ERV expression, suggesting that transcriptional reawakening is possible. HML-2 elements are reportedly induced during HIV-1 infection, but the conserved nature of these elements has, until recently, rendered their expression profiling problematic. Here, we provide comprehensive HERV-K HML-2 expression profiles specific for productively HIV-1-infected primary human CD4 <superscript>+</superscript> T cells. We combined enrichment of HIV-1 infected cells using a reporter virus expressing a surface reporter for gentle and efficient purification with long-read single-molecule real-time sequencing. We show that three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated on average between 3- and 5-fold in HIV-1-infected CD4 <superscript>+</superscript> T cells. One provirus, HML-2 12q24.33, in contrast, was repressed in the presence of active HIV replication. In conclusion, this report identifies the HERV-K HML-2 loci whose expression profiles differ upon HIV-1 infection in primary human CD4 <superscript>+</superscript> T cells. These data will help pave the way for further studies on the influence of endogenous retroviruses on HIV-1 replication. IMPORTANCE Endogenous retroviruses inhabit big portions of our genome. Moreover, although they are mainly inert, some of the evolutionarily younger members maintain the ability to express both RNA and proteins. We have developed an approach using long-read single-molecule real-time (SMRT) sequencing that produces long reads that allow us to obtain detailed and accurate HERV-K HML-2 expression profiles. We applied this approach to study HERV-K expression in the presence or absence of productive HIV-1 infection of primary human CD4 <superscript>+</superscript> T cells. In addition to using SMRT sequencing, our strategy also includes the magnetic selection of the infected cells so that levels of background expression due to uninfected cells are kept at a minimum. The results presented here provide a blueprint for in-depth studies of the interactions of the authentic upregulated HERV-K HML-2 elements and HIV-1.<br /> (Copyright © 2017 American Society for Microbiology.)
- Subjects :
- Cells, Cultured
Endogenous Retroviruses physiology
Genome, Human
HIV-1 genetics
Humans
Proviruses physiology
RNA, Viral metabolism
Viral Envelope Proteins metabolism
CD4-Positive T-Lymphocytes virology
Endogenous Retroviruses genetics
Gene Expression Regulation, Viral
HIV-1 physiology
Proviruses genetics
Viral Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 92
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 29046457
- Full Text :
- https://doi.org/10.1128/JVI.01507-17