A Virally Encoded DeSUMOylase Activity Is Required for Cytomegalovirus Reactivation from Latency.
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
A subset of viral genes is required for the long-term latent infection of hematopoietic cells by human cytomegalovirus (HCMV). Here, we show that a latency-associated gene product (LUNA) promotes the disruption of cellular PML bodies during latency. Mutation and inhibitor studies reveal that LUNA encodes a deSUMOylase activity responsible for this disruption. Specifically, LUNA encodes a conserved Asp-Cys-Gly motif common to all deSUMOylases. Importantly, mutation of the putative catalytic cysteine is sufficient to reverse LUNA-mediated PML dispersal and markedly reduces the efficiency of viral reactivation. The depletion of PML from cells is sufficient to rescue the reactivation of the LUNA-deficient viruses, arguing that targeting PML is an important biological role of LUNA. Finally, we demonstrate that reactivation of naturally latent HCMV is blocked by deSUMOylase inhibitors. Thus, latent HCMV primes the cellular environment for efficient reactivation via the activity of a virally encoded deSUMOylase.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2211-1247
Volume Title
Publisher
Publisher DOI
Sponsorship
Medical Research Council (G9202171)
Medical Research Council (MR/K021087/1)
MRC (G0900466/1)
Medical Research Council (MR/S00081X/1)