Skip to Main content Skip to Navigation
New interface
Preprints, Working Papers, ...

Clustering and reverse transcription of HIV-1 genomes in nuclear niches of macrophages

Abstract : In order to replicate, the Human Immunodeficiency Virus (HIV-1) reverse transcribes its RNA genome into DNA, which subsequently integrates into host cell chromosomes. These two key events of the viral life cycle are commonly viewed as separate not only in time but also in cellular space, since reverse transcription (RT) is thought to be completed in the cytoplasm before nuclear import and integration. However, the spatiotemporal organization of the early replication cycle in macrophages, natural nondividing target cells that constitute reservoirs of HIV-1 and an obstacle to curing AIDS, remains unclear. Here, we demonstrate that infected macrophages display large nuclear foci of viral DNA and viral RNA, in which multiple genomes cluster together. These clusters form in the absence of chromosomal integration, sequester the paraspeckle protein CPSF6 and localize to nuclear speckles. Strikingly, we show that viral RNA clusters consist mostly of genomic, incoming RNA, both in cells where RT is pharmacologically suppressed and in untreated cells. We demonstrate that, after temporary inhibition of RT, RT can resume in the nucleus and lead to vDNA accumulation in these clusters. We further show that nuclear RT can result in transcription competent viral DNA. These findings change our understanding of the early HIV-1 replication cycle, and may have implications for understanding HIV-1 persistence.
Document type :
Preprints, Working Papers, ...
Complete list of metadata

Cited literature [45 references]  Display  Hide  Download
Contributor : Marie Lemesle Connect in order to contact the contributor
Submitted on : Thursday, April 30, 2020 - 1:45:54 PM
Last modification on : Thursday, April 7, 2022 - 10:10:38 AM


Files produced by the author(s)






Elena Rensen, Florian Mueller, Viviana Scoca, Jyotsana Parmar, Philippe Souque, et al.. Clustering and reverse transcription of HIV-1 genomes in nuclear niches of macrophages. 2020. ⟨pasteur-02559460⟩



Record views


Files downloads