Inhibition of herpes simplex virus type 1 replication by adeno-associated virus rep proteins depends on their combined DNA-binding and ATPase/helicase activities.

Journal of Virology
Daniel L GlauserCornel Fraefel

Abstract

Adeno-associated virus (AAV) has previously been shown to inhibit the replication of its helper virus herpes simplex virus type 1 (HSV-1), and the inhibitory activity has been attributed to the expression of the AAV Rep proteins. In the present study, we assessed the Rep activities required for inhibition of HSV-1 replication using a panel of wild-type and mutant Rep proteins lacking defined domains and activities. We found that the inhibition of HSV-1 replication required Rep DNA-binding and ATPase/helicase activities but not endonuclease activity. The Rep activities required for inhibition of HSV-1 replication precisely coincided with the activities that were responsible for induction of cellular DNA damage and apoptosis, suggesting that these three processes are closely linked. Notably, the presence of Rep induced the hyperphosphorylation of a DNA damage marker, replication protein A (RPA), which has been reported not to be normally hyperphosphorylated during HSV-1 infection and to be sequestered away from HSV-1 replication compartments during infection. Finally, we demonstrate that the execution of apoptosis is not required for inhibition of HSV-1 replication and that the hyperphosphorylation of RPA per se is not inhibitory...Continue Reading

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Citations

Dec 15, 2015·Molecular Therapy. Methods & Clinical Development·Joseph M KelichWeidong Yang
Aug 21, 2015·Journal of Virology·Michael SeyffertCornel Fraefel
May 19, 2018·Nature Communications·Michel CrameriJovan Pavlovic
Jun 25, 2020·Viruses·Anita F MeierMichael Seyffert
May 1, 2021·International Journal of Molecular Sciences·Michael SeyffertCornel Fraefel

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