HIV-1 infection of primary CD4+ T cells regulates the expression of specific human endogenous retrovirus HERV-K (HML-2) elements

George R. Young, Sandra N. Terry, Lara Manganaro, Alvaro Cuesta-Dominguez, Gintaras Deikus, Dabeiba Bernal-Rubio, Laura Campisi, Ana Fernandez-Sesma, Robert Sebra, Viviana Simon, Lubbertus C.F. Mulder

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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+ 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+ 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+ T cells. These data will help pave the way for further studies on the influence of endogenous retroviruses on HIV-1 replication.

Original languageEnglish
Article numbere01507-17
JournalJournal of Virology
Volume92
Issue number1
DOIs
StatePublished - 1 Jan 2018

Keywords

  • CD4 T cells
  • HERV-K
  • HIV-1

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