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PXD055433

PXD055433 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleZika virus disrupts steroidogenesis and impairs spermatogenesis by stalling the translation of CYP17A1 mRNA
DescriptionZIKV 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.
HostingRepositoryiProX
AnnounceDate2024-08-29
AnnouncementXMLSubmission_2024-09-01_19:33:29.266.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterWei Yang
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-01 19:33:15ID requested
12024-09-01 19:33:29announced
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 affiliationWuhan University
contact email912813082@qq.com
lab head
Wei Yang
contact affiliationWuhan University
contact email912813082@qq.com
dataset submitter
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