ArticlePLoS pathogens2020
Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- A porcine model of chronic hepatitis E virus (HEV) infection identifies male reproductive glands as sites of viral persistence.Virulence · 2026Article
- Differential properties of NS1 glycoproteins in West Nile and Usutu viruses.Emerging microbes & infections · 2026Article
- Review
- Breaking barriers and beyond: Mechanisms and pathological implications of Zika virus traversal across blood-tissue interfaces.Virologica Sinica · 2026Review
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.Protein & cell · 2026Article
- Flavivirus NS1-triggered endothelial dysfunction promotes virus dissemination.PLoS pathogens · 2025Article
- Excess copper exposure and male reproductive toxicity: molecular mechanisms and potential interventions.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Hiding in plain sight: Genomic and phenotypic characterization of mosquito-borne Bussuquara virus.PLoS neglected tropical diseases · 2025Article
- Zika virus disrupts steroidogenesis and impairs spermatogenesis by stalling the translation of CYP17A1 mRNA.Nature communications · 2025Article
- Review
- A Primer on Proteomic Characterization of Intercellular Communication in a Virus Microenvironment.Molecular & cellular proteomics : MCP · 2025Review
- Sox9 downregulation in non-obstructive azoospermia by UTF1 and mediator role of POU5F1.BMC research notes · 2024Article
- ZIKV prM hijacks PIM1 kinase for phosphorylation to prevent ubiquitin-mediated degradation and facilitate viral replication.Frontiers in cellular and infection microbiology · 2024Article
- Article
- Transcription factorZoological research · 2023Article
- Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation.Nature communications · 2023Article
- Proteolytic regulation of a galectin-3/Lrp1 axis controls osteoclast-mediated bone resorption.The Journal of cell biology · 2023Article
- SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling.Nature communications · 2022Article
- The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zika virus (ZIKV) is a unique flavivirus with high tropism to the testes. ZIKV can persist in human semen for months and can cause testicular damage in male mice. However, the mechanisms through which ZIKV enters the testes remain unclear. In this study, we revealed that matrix metalloproteinase 9 (MMP9) was upregulated by ZIKV infection in cell culture and in A129 mice. Furthermore, using an in vitro Sertoli cell barrier model and MMP9-/- mice, we found that ZIKV infection directly affected the permeability of the blood-testis barrier (BTB), and knockout or inhibition of MMP9 reduced the effects of ZIKV on the Sertoli cell BTB, highlighting its role in ZIKV-induced disruption of the BTB. Interestingly, the protein levels of MMP9 were elevated by ZIKV nonstructural protein 1 (NS1) in primary mouse Sertoli cells (mSCs) and other cell lines. Moreover, the interaction between NS1 and MMP9 induced the K63-linked polyubiquitination of MMP9, which enhanced the stability of MMP9. The upregulated MMP9 level led to the degradation of essential proteins involved in the maintenance of the BTB, such as tight junction proteins (TJPs) and type Ⅳ collagens. Collectively, we concluded that ZIKV infection promoted the expression of MMP9 which was further stabilized by NS1 induced K63-linked polyubiquitination to affect the TJPs/ type Ⅳ collagen network, thereby disrupting the BTB and facilitating ZIKV entry into the testes.
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