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The nuclear lamina binds the EBV genome during latency and regulates viral gene expression
Caruso, Lisa Beatrice Guo, Rui Keith, Kelsey Madzo, Jozef Maestri, Davide Boyle, Sarah Kossenkov, Andrew Gewurz, Benjamin E.
Caruso, Lisa Beatrice
Guo, Rui
Keith, Kelsey
Madzo, Jozef
Maestri, Davide
Boyle, Sarah
Kossenkov, Andrew
Gewurz, Benjamin E.
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2022-04-14
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http://dx.doi.org/10.1371/journal.ppat.1010400
Abstract
The Epstein Barr virus (EBV) infects almost 95% of the population worldwide. While typically asymptomatic, EBV latent infection is associated with several malignancies of epithelial and lymphoid origin in immunocompromised individuals. In latently infected cells, the EBV genome persists as a chromatinized episome that expresses a limited set of viral genes in different patterns, referred to as latency types, which coincide with varying stages of infection and various malignancies. We have previously demonstrated that latency types correlate with differences in the composition and structure of the EBV episome. Several cellular factors, including the nuclear lamina, regulate chromatin composition and architecture. While the interaction of the viral genome with the nuclear lamina has been studied in the context of EBV lytic reactivation, the role of the nuclear lamina in controlling EBV latency has not been investigated. Here, we report that the nuclear lamina is an essential epigenetic regulator of the EBV episome. We observed that in B cells, EBV infection affects the composition of the nuclear lamina by inducing the expression of lamin A/C, but only in EBV+ cells expressing the Type III latency program. Using ChIP-Seq, we determined that lamin B1 and lamin A/C bind the EBV genome, and their binding correlates with deposition of the histone repressive mark H3K9me2. By RNA-Seq, we observed that knock-out of lamin A/C in B cells alters EBV gene expression. Our data indicate that the interaction between lamins and the EBV episome contributes to the epigenetic control of viral gene expression during latency, suggesting a restrictive function of the nuclear lamina as part of the host response against viral DNA entry into the nucleus.
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Caruso LB, Guo R, Keith K, Madzo J, Maestri D, Boyle S, et al. (2022) The nuclear lamina binds the EBV genome during latency and regulates viral gene expression. PLoS Pathog 18(4): e1010400. https://doi.org/10.1371/journal.ppat.1010400
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PLoS Pathogens, Vol. 18
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