PXD059264 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Keratin 72 restricts HIV-1 infection |
Description | Although HIV-1 can directly infect resting CD4+ T cells, virus replication in resting CD4+T cells is very inefficient owing to the different host restriction factors blocking viral replication. The accessory protein Vpx from the major simian immunodeficiency virus (SIV) of rhesus macaque (mac) and HIV-2 lineage could degrade a host restriction factor, SAM and HD domain containing protein 1 (SAMHD1), to facilitate HIV reverse transcription. Interestingly, Vpx proteins from a second SIV lineage, the SIV of redcapped mangabeys or mandrills (SIVrcm/nmd-2), had no effect on SAMHD1 and did not affect the dNTP pool, but strongly increased HIV-1 infection in resting CD4+ T cells although not in primary macrophages. This indicates that Vpx, in addition to SAMHD1,can overcome a previously unexplored restriction factor for lentiviruses. Here to identify this potential restriction factor, we examined Vpxrcm-interacting cellular proteins and found that keratin 72 (KRT72), an intermediate filament protein that is exclusively expressed in resting CD4+ T cells, is a new host antiviral factor targeted by Vpx. Other than Vpx from SIV mac and HIV-2, the Vpxrcm/nmd-2 lineage, which had no effect on the SAMHD1 protein, could strongly promote the degradation of KRT72, resulting in enhanced HIV-1 infection in resting CD4+ T cells. Furthermore, we discovered that KRT72 restricts HIV-1 replication by sequestering incoming HIV-1 capsids in cytoplasmic intermediate filaments (IFs). In the presence of KRT72, HIV-1 capsid cores become attached to the IF and their trafficking toward the nucleus is inhibited. In contrast, in the absence of KRT72, HIV-1 capsids are transported into the nucleus,leading to high levels of integrated HIV-1 DNA. In addition, KRT72 expression was substantially higher in resting CD4+ T cells than in activated CD4+ T cells, and it was rapidly reduced by T cell activation. Collectively, the results show that KRT72 is a new Vpx-counteracted host antiviral factor that acts to tether incoming capsids to the cytoplasmic IF, thereby restricting HIV-1 infection in resting CD4+ T cells. |
HostingRepository | PRIDE |
AnnounceDate | 2025-03-28 |
AnnouncementXML | Submission_2025-03-28_00:42:14.606.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | yang he |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-12-26 06:25:29 | ID requested | |
⏵ 1 | 2025-03-28 00:42:15 | announced | |
Publication List
Keyword List
submitter keyword: HIV-1,LC-MC,IP,KRT72,Vpx |
Contact List
Guoxin Liang |
contact affiliation | China Medical University |
contact email | gxliang@cmu.edu.cn |
lab head | |
yang he |
contact affiliation | China Medical University |
contact email | yhe91@cmu.edu.cn |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD059264
- Label: PRIDE project
- Name: Keratin 72 restricts HIV-1 infection