Latency-associated viral interleukin-10 (IL-10) encoded by human cytomegalovirus modulates cellular IL-10 and CCL8 Secretion during latent infection through changes in the cellular microRNA hsa-miR-92a.

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cam.issuedOnline2014-09-24
dc.contributor.authorPoole, Emma
dc.contributor.authorAvdic, Selmir
dc.contributor.authorHodkinson, Jemima
dc.contributor.authorJackson, Sarah
dc.contributor.authorWills, Mark
dc.contributor.authorSlobedman, Barry
dc.contributor.authorSinclair, John
dc.contributor.orcidPoole, Emma [0000-0003-3904-6121]
dc.contributor.orcidJackson, Sarah [0000-0002-4230-9220]
dc.contributor.orcidWills, Mark [0000-0001-8548-5729]
dc.contributor.orcidSinclair, John [0000-0002-2616-9571]
dc.date.accessioned2015-12-10T17:21:37Z
dc.date.available2015-12-10T17:21:37Z
dc.date.issued2014-12
dc.description.abstractUNLABELLED: The UL111A gene of human cytomegalovirus encodes a viral homologue of the cellular immunomodulatory cytokine interleukin 10 (cIL-10), which, due to alternative splicing, results in expression of two isoforms designated LAcmvIL-10 (expressed during both lytic and latent infection) and cmvIL-10 (identified only during lytic infection). We have analyzed the functions of LAcmvIL-10 during latent infection of primary myeloid progenitor cells and found that LAcmvIL-10 is responsible, at least in part, for the known increase in secretion of cellular IL-10 and CCL8 in the secretomes of latently infected cells. This latency-associated increase in CCL8 expression results from a concomitant LAcmvIL-10-mediated suppression of the expression of the cellular microRNA (miRNA) hsa-miR-92a, which targets CCL8 directly. Taking the data together, we show that the previously observed downregulation of hsa-miR-92a and upregulation of CCL8 during HCMV latent infection of myeloid cells are intimately linked via the latency-associated expression of LAcmvIL-10. IMPORTANCE: HCMV latency causes significant morbidity and mortality in immunocompromised individuals, yet HCMV is carried silently (latently) in 50 to 90% of the population. Understanding how HCMV maintains infection for the lifetime of an infected individual is critical for the treatment of immunocompromised individuals suffering with disease as a result of HCMV. In this study, we analyze one of the proteins that are expressed during the "latent" phase of HCMV, LAcmvIL-10, and find that the expression of the gene modulates the microenvironment of the infected cell, leading to evasion of the immune system.
dc.description.sponsorshipThis work was funded by a British Medical Research Council 5-year program grant (G0701279).
dc.description.versionThis is the final version of the article. It first appeared from the American Society for Microbiology via http://dx.doi.org/10.1128/JVI.02424-14
dc.identifier.citationPoole et al. Journal of Virology (2014) Vol. 88, 24, pp. 13947-55. doi: 10.1128/JVI.02424-14
dc.identifier.eissn1098-5514
dc.identifier.issn0022-538X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252954
dc.languageEnglish
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.publisher.urlhttp://dx.doi.org/10.1128/jvi.02424-14
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.rioxxterms.funderMRC
dc.rioxxterms.projectidG0701279
dc.subjectCells, Cultured
dc.subjectChemokine CCL8
dc.subjectCytomegalovirus
dc.subjectHumans
dc.subjectInterleukin-10
dc.subjectMicroRNAs
dc.subjectMyeloid Progenitor Cells
dc.subjectViral Proteins
dc.subjectVirus Latency
dc.titleLatency-associated viral interleukin-10 (IL-10) encoded by human cytomegalovirus modulates cellular IL-10 and CCL8 Secretion during latent infection through changes in the cellular microRNA hsa-miR-92a.
dc.typeArticle
prism.endingPage13955
prism.publicationDate2014
prism.publicationNameJ Virol
prism.startingPage13947
prism.volume88
pubs.funder-project-idMedical Research Council (MR/K021087/1)
pubs.funder-project-idMedical Research Council (G0701279)
rioxxterms.licenseref.startdate2014-09-24
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionofrecord10.1128/JVI.02424-14
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