SUMOylation of the human cytomegalovirus 72-kilodalton IE1 protein facilitates expression of the 86-kilodalton IE2 protein and promotes viral replication

Journal of Virology
Michael NevelsThomas Shenk

Abstract

The 72-kDa immediate-early 1 protein (IE1-72kDa) of human cytomegalovirus has been previously shown to be posttranslationally modified by covalent conjugation to the ubiquitin-related protein SUMO-1. Using an infectious bacterial artificial chromosome clone of human cytomegalovirus, we constructed a mutant virus (BADpmIE1-K450R) that is deficient for SUMOylation of IE1-72 kDa due to a single amino acid exchange in the SUMO-1 attachment site. Compared to wild-type virus, this mutant grew more slowly and generated a reduced yield in infected human fibroblasts, indicating that SUMO modification is required for the full activity of IE1-72 kDa. The lack of SUMOylation did not affect the intranuclear localization of IE1-72 kDa, including its ability to target to and disrupt PML bodies and to bind to mitotic chromatin. Likewise, SUMOylation-deficient IE1-72 kDa activated several viral promoters as efficiently as the wild-type protein. However, the failure to modify IE1-72 kDa resulted in substantially reduced levels of the IE2 transcript and its 86-kDa protein (IE2-86 kDa). These observations suggest that SUMO modification of IE1-72 kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86 kDa.

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Citations

Feb 8, 2013·Clinical and Vaccine Immunology : CVI·Thomas J GardnerDomenico Tortorella
Nov 11, 2011·Journal of Virology·Peter WimmerThomas Dobner
Dec 30, 2006·PLoS Biology·Leor S Weinberger, Thomas Shenk
Dec 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Michael NevelsThomas Shenk
Jan 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Atsushi OkumuraPaula M Pitha
Feb 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Christina PaulusMichael Nevels
Jul 4, 2006·Current Opinion in Microbiology·Roberto Boggio, Susanna Chiocca
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Jul 17, 2020·Frontiers in Cellular and Infection Microbiology·Sonali ChaturvediLeor Weinberger
Jan 11, 2019·Nature Communications·Maciej T NogalskiBenjamin D Greenbaum
Jul 19, 2006·The Journal of General Virology·Heejung KangJin-Hyun Ahn

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