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Kaposi’s sarcoma herpesvirus latency-associated nuclear antigen broadly regulates viral gene expression and is essential for lytic infection

2024Journal article Open access
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dc.contributor.authorLi, Shijun
dc.contributor.authorWang, Mengbo
dc.contributor.authorSciver, Nicholas Van
dc.contributor.authorSzymula, Agnieszka
dc.contributor.authorTumuluri, Vinayak Sadasivam
dc.contributor.authorGeorge, Athira
dc.contributor.authorRamachandran, Akshaya
dc.contributor.authorRaina, Komal
dc.contributor.authorCosta, Catarina N.
dc.contributor.authorZhao, Bo
dc.contributor.authorKazemian, Majid
dc.contributor.authorSimas, J. Pedro
dc.contributor.authorKaye, Kenneth M.
dc.date.accessioned2024-02-14T08:50:36Z
dc.date.available2024-02-14T08:50:36Z
dc.date.issued2024
dc.description.abstractKaposi’s sarcoma herpesvirus (KSHV) is a leading cause of malignancy in AIDS and current therapies are limited. Like all herpesviruses, KSHV infection can be latent or lytic. KSHV latency-associated nuclear antigen (LANA) is essential for viral genome persistence during latent infection. LANA also maintains latency by antagonizing expression and function of the KSHV lytic switch protein, RTA. Here, we find LANA null KSHV is not capable of lytic replication, indicating a requirement for LANA. While LANA promoted both lytic and latent gene expression in cells partially permissive for lytic infection, it repressed expression in non-permissive cells. Importantly, forced RTA expression in non-permissive cells led to induction of lytic infection and LANA switched to promote, rather than repress, most lytic viral gene expression. When basal viral gene expression levels were high, LANA promoted expression, but repressed expression at low basal levels unless RTA expression was forcibly induced. LANA’s effects were broad, but virus gene specific, extending to an engineered, recombinant viral GFP under control of host EF1α promoter, but not to host EF1α. Together, these results demonstrate that, in addition to its essential role in genome maintenance, LANA broadly regulates viral gene expression, and is required for high levels of lytic gene expression during lytic infection. Strategies that target LANA are expected to abolish KSHV infection.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1371/journal.ppat.1011907pt_PT
dc.identifier.eid85182774163
dc.identifier.issn1553-7366
dc.identifier.pmcPMC10793894
dc.identifier.pmid38232124
dc.identifier.urihttp://hdl.handle.net/10400.14/43935
dc.identifier.wos001150456500002
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleKaposi’s sarcoma herpesvirus latency-associated nuclear antigen broadly regulates viral gene expression and is essential for lytic infectionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titlePLoS Pathogenspt_PT
oaire.citation.volume20pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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