TY  - JOUR
AU  - Chen, Yuexuan
AU  - Klute, Susanne
AU  - Bansal, Anju
AU  - Sparrer, Konstantin Maria Johannes
AU  - Serra-Moreno, Ruth
TI  - HIV-1 Vpr is targeted for degradation by autophagy.
JO  - PLoS pathogens
VL  - 22
IS  - 3
SN  - 1553-7366
CY  - Lawrence, Kan.
PB  - PLoS
M1  - DZNE-2026-00266
SP  - e1014020
PY  - 2026
AB  - 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.
KW  - Autophagy: physiology
KW  - Humans
KW  - vpr Gene Products, Human Immunodeficiency Virus: metabolism
KW  - vpr Gene Products, Human Immunodeficiency Virus: genetics
KW  - HIV-1: metabolism
KW  - HIV-1: genetics
KW  - HIV-1: pathogenicity
KW  - HIV Infections: metabolism
KW  - HIV Infections: virology
KW  - HIV Infections: immunology
KW  - HEK293 Cells
KW  - Proteolysis
KW  - vpr Gene Products, Human Immunodeficiency Virus (NLM Chemicals)
KW  - vpr protein, Human immunodeficiency virus 1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41770818
C2  - pmc:PMC12970978
DO  - DOI:10.1371/journal.ppat.1014020
UR  - https://pub.dzne.de/record/285490
ER  -