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Journal of Virology, May 2009, p. 4030-4038, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02520-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Mouse Cytomegalovirus Immediate-Early 1 Gene Is Not Required for Establishment of Latency or for Reactivation in the Lungs{triangledown}

Andreas Busche,1 Anja Marquardt,1 Andre Bleich,2 Peter Ghazal,3 Ana Angulo,4 and Martin Messerle1*

Department of Virology,1 Institute of Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany,2 Division of Pathway Medicine, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom,3 Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain4

Received 8 December 2008/ Accepted 3 February 2009

The immediate-early protein IE1 of human and mouse cytomegalovirus (MCMV) is one of the first proteins expressed during the productive infection cycle and upon reactivation from latency. The CMV IE1 proteins have been found to inhibit histone deacetylases, suggesting a role in the epigenetic regulation of viral gene expression. Consequently, the IE1 protein is considered to have a profound effect on reactivation, because small amounts of IE1 may be decisive for the switch to lytic replication. Here we asked if an MCMV {Delta}ie1 mutant is able both to establish latency and to reactivate from the lungs of latently infected mice. Since the {Delta}ie1 mutant was known to be attenuated during acute infection, we first defined conditions that led to comparable levels of viral genomes during latent infection with mutant and wild-type (wt) MCMV. Viral genome copy numbers dropped considerably at the onset of the latent infection but then remained steady for both viruses even after several months. Reactivation of the {Delta}ie1 mutant and of wt MCMV from latency occurred with similar incidences in lung explant cultures at 4, 7, and 12 months postinfection. The increase in the frequency of a subset of MCMV-specific memory T cells, a possible indicator of frequent transcriptional reactivation events during latency, was in a comparable range for both viruses. Recurrence of the {Delta}ie1 virus infection in vivo could also be induced by hematoablative treatment of latently infected mice. We conclude that the ie1 gene is not essential for the establishment of latency or for the reactivation of MCMV.

* Corresponding author. Mailing address: Hannover Medical School, Department of Virology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Phone: 49-511-532-4320. Fax: 49-511-532-8736. E-mail: messerle.martin{at}mh-hannover.de

{triangledown} Published ahead of print on 11 February 2009.

Journal of Virology, May 2009, p. 4030-4038, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02520-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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