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bioRxiv · 10.1101/2022.08.12.503821

SIRT-1 connects autophagy and release of virus-containing vesicles during picornavirus infection

Jassey, A.·Logue, J.·Weston, S.·Wagner, M. A.·Galitska, G.·Miller, K. A.·Frieman, M. B.·Jackson, W. T.
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Abstract

Enterovirus D68 is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 inhibits autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1s proviral activity is, we demonstrate, mediated through the repression of ER stress. Inducing ER stress through thapsigargin treatment or SERCA2A knockdown in SIRT-1 knockdown cells had no additional effect on EV-D68 extracellular titers. Knockdown of SIRT-1 also decreases poliovirus and SARS-CoV-2 titers but not coxsackievirus B3. In non-lytic conditions, EV-D68 is primarily released in an enveloped form, and SIRT-1 is required for this process. Our data show that SIRT-1, through its translocation to the cytosol, is critical to promote the release of enveloped EV-D68 viral particles.

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Jassey, A., Logue, J., Weston, S., Wagner, M. A., Galitska, G., Miller, K. A., Frieman, M. B., Jackson, W. T.. 2022-08-15. SIRT-1 connects autophagy and release of virus-containing vesicles during picornavirus infection. https://doi.org/10.1101/2022.08.12.503821

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