Home > In process > HIV-1 Vpr is targeted for degradation by autophagy. > print

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024 7 _ |a 10.1371/journal.ppat.1014020
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037 _ _ |a DZNE-2026-00266
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Chen, Yuexuan
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245 _ _ |a HIV-1 Vpr is targeted for degradation by autophagy.
260 _ _ |a Lawrence, Kan.
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520 _ _ |a 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.
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650 _ 7 |a vpr Gene Products, Human Immunodeficiency Virus
|2 NLM Chemicals
650 _ 7 |a vpr protein, Human immunodeficiency virus 1
|2 NLM Chemicals
650 _ 2 |a Autophagy: physiology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a vpr Gene Products, Human Immunodeficiency Virus: metabolism
|2 MeSH
650 _ 2 |a vpr Gene Products, Human Immunodeficiency Virus: genetics
|2 MeSH
650 _ 2 |a HIV-1: metabolism
|2 MeSH
650 _ 2 |a HIV-1: genetics
|2 MeSH
650 _ 2 |a HIV-1: pathogenicity
|2 MeSH
650 _ 2 |a HIV Infections: metabolism
|2 MeSH
650 _ 2 |a HIV Infections: virology
|2 MeSH
650 _ 2 |a HIV Infections: immunology
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Proteolysis
|2 MeSH
700 1 _ |a Klute, Susanne
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700 1 _ |a Bansal, Anju
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700 1 _ |a Sparrer, Konstantin Maria Johannes
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700 1 _ |a Serra-Moreno, Ruth
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773 _ _ |a 10.1371/journal.ppat.1014020
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