Skip to Main content Skip to Navigation
Journal articles

Uracil DNA glycosylase interacts with the p32 subunit of the replication protein A complex to modulate HIV-1 reverse transcription for optimal virus dissemination

Abstract : Background: Through incorporation into virus particles, the HIV‑1 Vpr protein participates in the early steps of the virus life cycle by influencing the reverse transcription process. We previously showed that this positive impact on reverse transcription was related to Vpr binding to the uracil DNA glycosylase 2 enzyme (UNG2), leading to enhance‑ ment of virus infectivity in established CD4‑positive cell lines via a nonenzymatic mechanism. Results: We report here that Vpr can form a trimolecular complex with UNG2 and the p32 subunit (RPA32) of the replication protein A (RPA) complex and we explore how these cellular proteins can influence virus replication and dissemination in the primary target cells of HIV‑1, which express low levels of both proteins. Virus infectivity and replication in peripheral blood mononuclear cells and monocyte‑derived macrophages (MDMs), as well as the efficiency of the viral DNA synthesis, were significantly reduced when viruses were produced from cells depleted of endogenous UNG2 or RPA32. Moreover, viruses produced in macrophages failed to replicate efficiently in UNG2‑ and RPA32‑depleted T lymphocytes. Reciprocally, viruses produced in UNG2‑depleted T cells did not replicate efficiently in MDMs confirming the positive role of UNG2 for virus dissemination. Conclusions: Our data show the positive effect of UNG2 and RPA32 on the reverse transcription process leading to optimal virus replication and dissemination between the primary target cells of HIV‑1.
Document type :
Journal articles
Complete list of metadatas

Cited literature [63 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01322757
Contributor : Mireille Bos <>
Submitted on : Friday, May 27, 2016 - 4:09:23 PM
Last modification on : Thursday, April 9, 2020 - 11:50:51 AM
Long-term archiving on: : Sunday, August 28, 2016 - 10:42:26 AM

File

12977_2016_Article_257.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Cecile Herate, Clarisse Vigne, Marie Lambele, Marie‑christine Rouyez, Serge Benichou. Uracil DNA glycosylase interacts with the p32 subunit of the replication protein A complex to modulate HIV-1 reverse transcription for optimal virus dissemination. Retrovirology, BioMed Central, 2016, 13 (26), ⟨10.1186/s12977-016-0257-x⟩. ⟨inserm-01322757⟩

Share

Metrics

Record views

498

Files downloads

1039