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

Shijun Li, Mengbo Wang, Nicholas Van Sciver, Agnieszka Szymula, Vinayak Sadasivam Tumuluri, Athira George, Akshaya Ramachandran, Komal Raina, Catarina N. Costa, Bo Zhao, Majid Kazemian, J. Pedro Simas*, Kenneth M. Kaye*

*Autor correspondente para este trabalho

Resultado de pesquisarevisão de pares

2 Citações (Scopus)
21 Transferências (Pure)

Resumo

Kaposi’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.

Idioma originalEnglish
Número do artigoe1011907
Número de páginas24
RevistaPLoS Pathogens
Volume20
Número de emissão1
DOIs
Estado da publicaçãoPublicado - 17 jan. 2024

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