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KSHV LANA acetylation-selective acidic domain reader sequence mediates virus persistence

2020-09-08Journal article Open access
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dc.contributor.authorJuillard, Franceline
dc.contributor.authorMiranda, Marta Pires de
dc.contributor.authorLi, Shijun
dc.contributor.authorFranco, Aura
dc.contributor.authorSeixas, André F.
dc.contributor.authorLiu, Bing
dc.contributor.authorÁlvarez, Ángel L.
dc.contributor.authorTan, Min
dc.contributor.authorSzymula, Agnieszka
dc.contributor.authorKaye, Kenneth M.
dc.contributor.authorSimas, J. Pedro
dc.date.accessioned2021-03-17T16:07:30Z
dc.date.available2021-03-17T16:07:30Z
dc.date.issued2020-09-08
dc.description.abstractViruses modulate biochemical cellular pathways to permit infection. A recently described mechanism mediates selective protein interactions between acidic domain readers and unacetylated, lysine-rich regions, opposite of bromodomain function. Kaposi´s sarcoma (KS)-associated herpesvirus (KSHV) is tightly linked with KS, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV latently infects cells, and its genome persists as a multicopy, extrachromosomal episome. During latency, KSHV expresses a small subset of genes, including the latency-associated nuclear antigen (LANA), which mediates viral episome persistence. Here we show that LANA contains two tandem, partially overlapping, acidic domain sequences homologous to the SET oncoprotein acidic domain reader. This domain selectively interacts with unacetylated p53, as evidenced by reduced LANA interaction after overexpression of CBP, which acetylates p53, or with an acetylation mimicking carboxyl-terminal domain p53 mutant. Conversely, the interaction of LANA with an acetylation-deficient p53 mutant is enhanced. Significantly, KSHV LANA mutants lacking the acidic domain reader sequence are deficient for establishment of latency and persistent infection. This deficiency was confirmed under physiological conditions, on infection of mice with a murine gammaherpesvirus 68 chimera expressing LANA, where the virus was highly deficient in establishing latent infection in germinal center B cells. Therefore, LANA’s acidic domain reader is critical for viral latency. These results implicate an acetylation-dependent mechanism mediating KSHV persistence and expand the role of acidic domain readers.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1073/pnas.2004809117pt_PT
dc.identifier.eid85090613569
dc.identifier.issn0027-8424
dc.identifier.pmcPMC7486799
dc.identifier.pmid32820070
dc.identifier.urihttp://hdl.handle.net/10400.14/32248
dc.identifier.wos000571476400005
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAcetylation-regulated interactionpt_PT
dc.subjectAcidic domain readerpt_PT
dc.subjectKaposi's sarcoma herpesviruspt_PT
dc.subjectLatency-associated nuclear antigenpt_PT
dc.subjectVirus persistencept_PT
dc.titleKSHV LANA acetylation-selective acidic domain reader sequence mediates virus persistencept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage22451pt_PT
oaire.citation.issue36pt_PT
oaire.citation.startPage22443pt_PT
oaire.citation.titleProceedings of the National Academy of Sciences of the United States of Americapt_PT
oaire.citation.volume117pt_PT
person.familyNamePires de Miranda
person.familyNameÁlvarez
person.familyNameSimas
person.givenNameMarta
person.givenNameÁngel L.
person.givenNameJ Pedro
person.identifier1061776
person.identifier.ciencia-id8A1D-8B1A-205B
person.identifier.ciencia-idF415-6379-78FB
person.identifier.ciencia-id3513-BF02-52B7
person.identifier.orcid0000-0003-3733-4963
person.identifier.orcid0000-0001-9388-8595
person.identifier.orcid0000-0001-6982-9253
person.identifier.ridB-2004-2015
person.identifier.scopus-author-id14008468100
person.identifier.scopus-author-id35069014500
person.identifier.scopus-author-id7003457329
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7c13d360-9783-400c-a167-1dc27a2fcdf0
relation.isAuthorOfPublicationa6f37a34-10a0-44b2-b42f-7019436225fb
relation.isAuthorOfPublicationb3171337-3c36-4d2d-8af5-e7da208599a0
relation.isAuthorOfPublication.latestForDiscoveryb3171337-3c36-4d2d-8af5-e7da208599a0

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