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Article

The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding

1
School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia
2
Institute of Respiratory Health, University of Western Australia, Nedlands, WA 6009, Australia
3
Department for Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
*
Author to whom correspondence should be addressed.
Current Address: School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.
Current Address: SpeedX Pty Ltd., National Innovative Centre, Evenleigh, NSW 2015, Australia.
Academic Editors: Niels A. Lemmermann and Vanda Juranic Lisnic
Pathogens 2021, 10(7), 866; https://doi.org/10.3390/pathogens10070866
Received: 16 June 2021 / Revised: 7 July 2021 / Accepted: 8 July 2021 / Published: 9 July 2021
(This article belongs to the Special Issue Murine Models of Cytomegalovirus Infection)
As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3′-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNγ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells. View Full-Text
Keywords: cytomegalovirus; immune evasion; m15; natural killer; coterminal transcription; salivary gland; saliva shedding cytomegalovirus; immune evasion; m15; natural killer; coterminal transcription; salivary gland; saliva shedding
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MDPI and ACS Style

Chan, B.; Arapović, M.; Masters, L.L.; Rwandamuiye, F.; Jonjić, S.; Smith, L.M.; Redwood, A.J. The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding. Pathogens 2021, 10, 866. https://doi.org/10.3390/pathogens10070866

AMA Style

Chan B, Arapović M, Masters LL, Rwandamuiye F, Jonjić S, Smith LM, Redwood AJ. The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding. Pathogens. 2021; 10(7):866. https://doi.org/10.3390/pathogens10070866

Chicago/Turabian Style

Chan, Baca, Maja Arapović, Laura L. Masters, Francois Rwandamuiye, Stipan Jonjić, Lee M. Smith, and Alec J. Redwood. 2021. "The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding" Pathogens 10, no. 7: 866. https://doi.org/10.3390/pathogens10070866

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