Why the study?
Although efficient alphavirus replication requires catalytically active macrodomains, which form of ADP-ribosylation requires removal and from which protein(s) had not been determined.
Poly-ARH activity of viral macrodomains is essential for efficient alphavirus replication, highlighting a potential therapeutic target.
Alphavirus replication requires catalytically active macrodomain; leaves open therapeutic targeting across conserved viral families.
Viral macrodomains have drawn attention in recent years due to their high degree of conservation in several virus families (e.g., coronaviruses and alphaviruses) and their potential druggability. These domains erase mono- or poly-ADP-ribose, posttranslational modifications written by host poly-ADP-ribose polymerase (PARP) proteins, from undetermined host or viral proteins to enhance replication. Prior work determined that efficient alphavirus replication requires catalytically active macrodomains; however, which form of the modification requires removal and from which protein(s) had not been determined. Here, we present evidence for the specific requirement of poly-ARH activity to ensure efficient productive infection and virus replication.
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Aguilar et al. (2022) studied this question.
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