PXD055433

PXD055433 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-01 19:33:15	ID requested
⏵ 1	2024-09-01 19:33:29	announced

Dataset with its publication pending

submitter keyword: Zika Virus, Pathogenesis, Host-virus interaction, Spermatogenesis

Steroidogenesis

Testosterone

CYP17A1

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

iProX dataset URI