ArticleJournal of virology2014
Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine reproductive and respiratory syndrome virus entry.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- Review
- Potential threats of porcine Getah virus outbreaks and its specific antagonism of host antiviral response through proteasome-dependent degradation of P46 by nsP2.PLoS pathogens · 2026Article
- Metal binding site alignment enables network-driven discovery of recurrent geometries across sequence-divergent proteins and drug off-targets.PLoS computational biology · 2026Article
- CD163 at the crossroads: a viral-exploited immunomodulator.Virology journal · 2026Review
- Article
- Review
- Early boosting of p38 MAPK signaling pathway by lycorine hydrochloride potently inhibits PRRSV proliferation in primary and established cells.Frontiers in microbiology · 2025Article
- Antiviral effects of mogroside V against porcine reproductive and respiratory syndrome virusFrontiers in microbiology · 2025Article
- Elevation of IL-8 secretion induced by PEDV infection via NF-κB signaling pathway.Frontiers in cellular and infection microbiology · 2024Article
- Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3.PLoS pathogens · 2023Article
- Review
- Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism.iScience · 2023Article
- Glycoprotein Non-Metastatic Melanoma Protein B Restricts PRRSV Replication by Inhibiting Autophagosome-Lysosome Fusion.Viruses · 2023Article
- Review
- Porcine deltacoronavirus E protein induces interleukin-8 production via NF-κB and AP-1 activation.Veterinary microbiology · 2022Article
- Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection.Viruses · 2022Article
- Toosendanin activates caspase-1 and induces maturation of IL-1β to inhibit type 2 porcine reproductive and respiratory syndrome virus replication via an IFI16-dependent pathway.Veterinary research · 2022Article
- Innate Immune Evasion of Porcine Epidemic Diarrhea Virus through Degradation of the FBXW7 Protein via the Ubiquitin-Proteasome Pathway.Journal of virology · 2022Article
- Recent advances in inhibition of porcine reproductive and respiratory syndrome virus through targeting CD163.Frontiers in microbiology · 2022Review
- Reappraising host cellular factors involved in attachment and entry to develop antiviral strategies against porcine reproductive and respiratory syndrome virus.Frontiers in microbiology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledAs a consequence of their effects on ectodomain shedding, members of the A disintegrin and metalloprotease (ADAM) family have been implicated in the control of various cellular processes. Although ADAM family members are also involved in cancer, inflammation, and other pathologies, it is unclear whether they affect porcine reproductive and respiratory syndrome virus (PRRSV) infection. Here, we demonstrate for the first time that inhibition of ADAM17 enhances PRRSV entry in Marc-145 and porcine alveolar macrophages (PAMs). We also demonstrate that the inhibition of ADAM17 upregulates membrane CD163 expression, a putative PRRSV receptor that is exogenously expressed in BHK-21 and endogenously expressed in Marc-145 and PAMs. Furthermore, overexpression of ADAM17 induced downregulation of CD163 expression and a reduction in PRRSV infection, whereas ablation of ADAM17 expression using specific small interfering RNA resulted in upregulation of CD163 expression with a corresponding increase in PRRSV infection. These ADAM17-mediated effects were confirmed with PRRSV nonpermissive BHK-21 cells transfected with CD163 cDNA. Overall, these findings indicate that ADAM17 downregulates CD163 expression and hinders PRRSV entry. Hence, downregulation of ADAM17 particular substrates may be an additional component of the anti-infection defenses. IMPORTANCE: ADAM17 is one of the important membrane-associated metalloproteases that mediate various cellular events, as well as inflammation, cancer, and other pathologies. Here, we investigate for the first time the role of the metalloprotease ADAM17 in PRRSV infection. By using inhibitor and genetic modification methods, we demonstrate that ADAM17 negatively regulate PRRSV entry by regulating its substrate(s). More specifically, ADAM 17 mediates the downregulation of the PRRSV cellular receptor CD163. The reduction in CD163 expression represents another component of the anti-infection response initiated by ADAM17.
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