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@ARTICLE{Chen:285490,
author = {Chen, Yuexuan and Klute, Susanne and Bansal, Anju and
Sparrer, Konstantin Maria Johannes and Serra-Moreno, Ruth},
title = {{HIV}-1 {V}pr is targeted for degradation by autophagy.},
journal = {PLoS pathogens},
volume = {22},
number = {3},
issn = {1553-7366},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {DZNE-2026-00266},
pages = {e1014020},
year = {2026},
abstract = {Autophagy is part of the innate immune arsenal to fight
viruses, including HIV-1. We previously reported that HIV-1
Gag is targeted for autophagy-mediated degradation. Here, we
identify HIV-1 Vpr, an important virulence factor, as an
autophagy target in HIV-1 NL4-3, a lab adapted molecular
clone. Notably, Vpr proteins from a collection of
transmitted/founder viruses (TFVs) were resistant to
autophagy. Based on this observation, we identified residues
at positions 37, 45, 77, 83-86, 93-94 in NL4-3 Vpr as
responsible for its susceptibility to autophagy.
Importantly, differences between NL4-3 and TFV Vpr proteins
at these positions impact their interaction with the
autophagy receptors NDP52, SQSTM1/p62 and TAX1BP1. By
engineering NL4-3 molecular clones harboring either
autophagy-sensitive or -resistant vpr, we found that in 2D
and 3D in vitro systems virus spread was significantly
reduced for the virus carrying autophagy-sensitive Vpr. In
conclusion, our study identifies Vpr as a novel autophagy
target and suggests that Vpr susceptibility to autophagy
impacts HIV-1 spread.},
keywords = {Autophagy: physiology / Humans / vpr Gene Products, Human
Immunodeficiency Virus: metabolism / vpr Gene Products,
Human Immunodeficiency Virus: genetics / HIV-1: metabolism /
HIV-1: genetics / HIV-1: pathogenicity / HIV Infections:
metabolism / HIV Infections: virology / HIV Infections:
immunology / HEK293 Cells / Proteolysis / vpr Gene Products,
Human Immunodeficiency Virus (NLM Chemicals) / vpr protein,
Human immunodeficiency virus 1 (NLM Chemicals)},
cin = {AG Sparrer},
ddc = {610},
cid = {I:(DE-2719)1910003},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41770818},
pmc = {pmc:PMC12970978},
doi = {10.1371/journal.ppat.1014020},
url = {https://pub.dzne.de/record/285490},
}