Skip to Main content Skip to Navigation
Journal articles

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

Abstract : In order to replicate, 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 viral replication cycle in macrophages, the natural non-dividing 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 (vDNA) and viral RNA, in which multiple viral genomes cluster together. These clusters form in the absence of chromosomal integration, sequester the paraspeckle protein CPSF6, and localize to nuclear speckles. Surprisingly, these viral RNA clusters consist mostly of genomic, incoming RNA, both in cells where reverse transcription is pharmacologically suppressed and in untreated cells. We demonstrate that following temporary inhibition, reverse transcription can resume in the nucleus and lead to vDNA accumulation in these clusters. We further show that nuclear reverse transcription can result in transcription-competent viral DNA. These findings change our understanding of the early HIV-1 replication cycle and may have implications for addressing HIV-1 persistence.
Document type :
Journal articles
Complete list of metadata
Contributor : Francesca Di Nunzio Connect in order to contact the contributor
Submitted on : Saturday, December 26, 2020 - 11:27:29 AM
Last modification on : Thursday, April 7, 2022 - 10:10:54 AM
Long-term archiving on: : Monday, March 29, 2021 - 4:43:02 PM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License




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. EMBO Journal, EMBO Press, 2021, 40 (1), pp.e105247. ⟨10.15252/embj.2020105247⟩. ⟨pasteur-03088393⟩



Record views


Files downloads