%0 Journal Article
%A Chen, Yuexuan
%A Klute, Susanne
%A Bansal, Anju
%A Sparrer, Konstantin Maria Johannes
%A Serra-Moreno, Ruth
%T HIV-1 Vpr is targeted for degradation by autophagy.
%J PLoS pathogens
%V 22
%N 3
%@ 1553-7366
%C Lawrence, Kan.
%I PLoS
%M DZNE-2026-00266
%P e1014020
%D 2026
%X 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.
%K Autophagy: physiology
%K Humans
%K vpr Gene Products, Human Immunodeficiency Virus: metabolism
%K vpr Gene Products, Human Immunodeficiency Virus: genetics
%K HIV-1: metabolism
%K HIV-1: genetics
%K HIV-1: pathogenicity
%K HIV Infections: metabolism
%K HIV Infections: virology
%K HIV Infections: immunology
%K HEK293 Cells
%K Proteolysis
%K vpr Gene Products, Human Immunodeficiency Virus (NLM Chemicals)
%K vpr protein, Human immunodeficiency virus 1 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41770818
%2 pmc:PMC12970978
%R 10.1371/journal.ppat.1014020
%U https://pub.dzne.de/record/285490