Host ADP-ribosylation and the SARS-CoV-2 macrodomain

Autor(es)

Hoch, Nicolas C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem, Sao Paulo - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: BIOCHEMICAL SOCIETY TRANSACTIONS; v. 49, n. 4, p. 1711-1721, AUG 2021.
• Citações Web of Science: 0

Resumo

The COVID-19 pandemic has prompted intense research efforts into elucidating mechanisms of coronavirus pathogenesis and to propose antiviral interventions. The interferon (IFN) response is the main antiviral component of human innate immunity and is actively suppressed by several non-structural SARS-CoV-2 proteins, allowing viral replication within human cells. Differences in IFN signalling efficiency and timing have emerged as central determinants of the variability of COVID-19 disease severity between patients, highlighting the need for an improved understanding of host-pathogen interactions that affect the IFN response. ADP-ribosylation is an underexplored post-translational modification catalyzed by ADP-ribosyl transferases collectively termed poly(ADP-ribose) poly-merases (PARPs). Several human PARPs are induced by the IFN response and participate in antiviral defences by regulating IFN signalling itself, modulating host processes such as translation and protein trafficking, as well as directly modifying and inhibiting viral target proteins. SARS-CoV-2 and other viruses encode a macrodomain that hydrolyzes ADP-ribose modifications, thus counteracting antiviral PARP activity. This mini-review provides a brief overview of the known targets of IFN-induced ADP-ribosylation and the functions of viral macrodomains, highlighting several open questions in the field. (AU)

• Processo FAPESP: 18/18007-5 - ADP-ribosilação de proteínas: sinalização de danos ao DNA e impactos na saúde humana
• Beneficiário: Nicolas Carlos Hoch
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/05317-6 - Inibição do macrodomínio viral como estratégia de tratamento para Coronavírus
• Beneficiário: Nicolas Carlos Hoch
• Modalidade de apoio: Auxílio à Pesquisa - Regular