A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation

Abstract

Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.

References 53

1. 1.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1093/oxfordjournals.jbchem.a021588

2. 2.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1002/j.1460-2075.1995.tb07299.x

3. 3.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1242/jcs.079889

4. 4.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1128/jvi.00239-10

5. 5.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1002/rmv.657

6. 6.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1016/0042-6822(81)90201-4

7. 7.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1128/jvi.01118-06

8. 8.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1128/jvi.01294-10

9. 9.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library10.1073/pnas.89.8.3443

10. 10.
    Transforming Growth Factor-β: Activation by Neuraminidase and Role in Highly Pathogenic H5N1 Influenza Pathogenesis · 2010

    No notice
11. 11.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1055/s-0033-1334487

12. 12.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

13. 13.
    Influenza HA Subtypes Demonstrate Divergent Phenotypes for Cleavage Activation and pH of Fusion: Implications for Host Range and Adaptation · 2013

    No notice
14. 14.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1128/jvi.02232-10

15. 15.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.4049/jimmunol.176.11.6962

16. 16.
    Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice · 2013

    Corrected
17. 17.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1074/jbc.m109.091256

18. 18.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1128/jvi.68.9.6074-6078.1994

19. 19.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1101/gr.gr-1478r

20. 20.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1161/01.res.0000250834.29108.1a

21. 21.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1016/j.bbapap.2011.07.001

22. 22.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1016/0042-6822(75)90284-6

23. 23.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1074/jbc.m408608200

24. 24.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

25. 25.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1016/0042-6822(75)90285-8

26. 26.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1016/0042-6822(73)90296-1

27. 27.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1128/jvi.67.4.2110-2122.1993

28. 28.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1007/bf01718208

29. 29.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1073/pnas.221447598

30. 30.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1074/jbc.m111.319996

31. 31.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1111/j.1538-7836.2007.02464.x

32. 32.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1038/nature06553

33. 33.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1073/pnas.83.18.6776

34. 34.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1021/bi0107290

35. 35.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.4049/jimmunol.180.5.3391

36. 36.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1128/jvi.03677-13

37. 37.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1146/annurev-immunol-032713-120231

38. 38.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1038/nature09907

39. 39.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1038/nature12862

40. 40.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library10.1073/pnas.72.1.93

Cited by papers we hold 3

• Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS‐CoV‐2 in the respiratory tract · 2021
  Not checked
• Identification of interferon-stimulated genes that attenuate Ebola virus infection · 2020
  Not checked
• LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step · 2018
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.