A Virally Encoded DeSUMOylase Activity Is Required for Cytomegalovirus Reactivation from Latency.
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Authors
Kew, Verity G
Lau, Jonathan CH
Murray, Matthew J
Stamminger, Thomas
Reeves, Matthew B
Publication Date
2018-07-17Journal Title
Cell Rep
ISSN
2211-1247
Publisher
Elsevier BV
Volume
24
Issue
3
Pages
594-606
Language
eng
Type
Article
Physical Medium
Print
Metadata
Show full item recordCitation
Poole, E., Kew, V. G., Lau, J. C., Murray, M. J., Stamminger, T., Sinclair, J., & Reeves, M. B. (2018). A Virally Encoded DeSUMOylase Activity Is Required for Cytomegalovirus Reactivation from Latency.. Cell Rep, 24 (3), 594-606. https://doi.org/10.1016/j.celrep.2018.06.048
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.
Keywords
Dendritic Cells, Inclusion Bodies, Humans, Cytomegalovirus, Carbon-Nitrogen Lyases, Viral Proteins, Antigens, CD34, Virus Latency, Virus Activation, Amino Acid Sequence, Catalytic Domain, Mutation, THP-1 Cells
Sponsorship
Medical Research Council (G0701279)
Medical Research Council (G9202171)
Medical Research Council (MR/K021087/1)
MRC (G0900466/1)
Medical Research Council (MR/S00081X/1)
Identifiers
External DOI: https://doi.org/10.1016/j.celrep.2018.06.048
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283522
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