PXD055433-1
PXD055433 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Zika virus disrupts steroidogenesis and impairs spermatogenesis by stalling the translation of CYP17A1 mRNA |
Description | ZIKV infection is associated with testicular damage and abnormal spermatogenesis. However, the molecular mechanisms underlying these pathogenic processes remain unclear. Here, we demonstrate that ZIKV disrupts Leydig cells' ability to produce testosterone, leading to decreased sperm counts and motility. Specifically, the non-structural protein NS2A of ZIKV downregulates testosterone production by directly binding to mRNA of CYP17A1, a key enzyme in testosterone synthesis, thereby inhibiting its translation. Notably, the sole membrane-traversing segment and its flanking loops of NS2A are crucial for this interaction with CYP17A1 mRNA. Scanning mutagenesis studies within this sequence identified amino acid residues critical for NS2A binding and the suppression of CYP17A1 mRNA translation. Testicular inoculation of adeno-associated virus (AAV) delivering ZIKV-NS2A or its mutant showed that ZIKV-NS2A alone is sufficient to affect steroidogenesis and spermatogenesis in vivo. Moreover, a mutant virus generated by reverse genetics, containing a single amino acid mutation that abolishes NS2A’s binding to CYP17A1 mRNA, exhibited significantly lower inhibition of steroidogenesis and spermatogenesis compared to the wild-type virus in mouse models. These findings enhance our understanding of how ZIKV impacts male reproductive health and provide crucial insights for future preventive and therapeutic strategies. |
HostingRepository | iProX |
AnnounceDate | 2024-08-29 |
AnnouncementXML | Submission_2024-09-01_19:33:29.266.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Wei Yang |
SpeciesList | scientific name: Mus musculus; NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | TripleTOF 5600 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-09-01 19:33:15 | ID requested | |
⏵ 1 | 2024-09-01 19:33:29 | announced |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Zika Virus, Pathogenesis, Host-virus interaction, Spermatogenesis |
Steroidogenesis |
Testosterone |
CYP17A1 |
Contact List
Wei Yang | |
---|---|
contact affiliation | Wuhan University |
contact email | 912813082@qq.com |
lab head | |
Wei Yang | |
contact affiliation | Wuhan University |
contact email | 912813082@qq.com |
dataset submitter |
Full Dataset Link List
iProX dataset URI |