Unknown

Dataset Information

0

HIV-1 Vpu induces neurotoxicity by promoting Caspase 3-dependent cleavage of TDP-43


ABSTRACT: Despite the efficacy of highly active antiretroviral therapy in controlling the incidence and mortality of AIDS, effective interventions for HIV-1-induced neurological damage and cognitive impairment remain elusive. In this study, we found that HIV-1 infection can induce proteolytic cleavage and aberrant aggregation of TAR DNA-binding protein 43 (TDP-43), a pathological protein associated with various severe neurological disorders. The HIV-1 accessory protein Vpu was found to be responsible for the cleavage of TDP-43, as ectopic expression of Vpu alone was sufficient to induce TDP-43 cleavage, whereas HIV-1 lacking Vpu failed to cleave TDP-43. Mechanistically, the cleavage of TDP-43 at Asp89 by HIV-1 relies on Vpu-mediated activation of Caspase 3, and pharmacological inhibition of Caspase 3 activity effectively suppressed the HIV-1-induced aggregation and neurotoxicity of TDP-43. Overall, these results suggest that TDP-43 is a conserved host target of HIV-1 Vpu and provide evidence for the involvement of TDP-43 dysregulation in the neural pathogenesis of HIV-1.

SUBMITTER: Dr. Jiaxin Yang 

PROVIDER: S-SCDT-10_1038-S44319-024-00238-Y | biostudies-other |

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC10134869 | biostudies-literature
| S-EPMC8169680 | biostudies-literature
| S-EPMC9998009 | biostudies-literature
| S-EPMC4478251 | biostudies-literature
| S-EPMC6673167 | biostudies-literature
2013-01-22 | E-GEOD-42844 | biostudies-arrayexpress
| S-EPMC3584124 | biostudies-literature
2013-01-22 | GSE42844 | GEO
| S-EPMC4756693 | biostudies-literature
| S-EPMC4596857 | biostudies-literature