SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses

[tetano]

Virology. 2020 Jan 7;543:43-53. doi: 10.1016/j.virol.2020.01.004. [Epub ahead of print] SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.

Straus MR¹, Kinder JT², Segall M³, Dutch RE⁴, Whittaker GR⁵.
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Abstract

Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 h post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral.
Copyright ? 2020 Elsevier Inc. All rights reserved.


KEYWORDS:

Antiviral therapy; HAI-2; HMPV; HMPV F; Hemagglutinin; Influenza; Proteases; SPINT2

PMID: 32056846 DOI: 10.1016/j.virol.2020.01.004