Please use this identifier to cite or link to this item: https://covid-19.conacyt.mx/jspui/handle/1000/1629
The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression
Grunewald, M
Chen, Y
Kuny, C
Maejima, T
Lease, R
Ferraris, D
Aikawa, M
Sullivan, C
Perlman, S
Fehr, A
Acceso Abierto
Atribución-NoComercial-SinDerivadas
ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production.
PLoS Pathogens
2019
Preimpreso
https://coronavirus.1science.com/item/b19a33b47b4db6d484784efc2ba56f96f884e1cb
Inglés
VIRUS RESPIRATORIOS
Appears in Collections:Artículos científicos

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