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Nanoparticle exposure of persistently herpesvirus-infected cells reactivates latent virus and restores a signature observed during acute virus infection in vitro and in vivo

ABSTRACT: Both inhalation of environmental (nano)particles (NP) and persistent herpesvirus-infection have been implicated to contribute to the development of chronic lung disease. We hypothesized that the combination of NP exposure and virus infection leads to a different outcome than each factor alone. To test this hypothesis, we applied different carbonaceous NP in the model system of murine gammaherpesvirus 68 (MHV-68), which serves as a small animal model for gammaherpesvirus pathogenesis in vitro and in vivo. NP exposure of latently infected cells induced lytic virus production, while virus growth after de novo infection was not affected. To investigate the effect of pulmonary NP exposure in vivo, latently infected mice were instilled with carbonaceous NP or left untreated. After 24 hours, lung tissue was harvested for analysis. Immunohistochemistry demonstrated an increase in lytic viral proteins after exposure to NP. Simultaneously, gene expression analysis revealed a signature with considerable parallels to the one seen during acute infection. Analysis of the metabolome demonstrated an enrichment of phospholipids in latently infected mice after short-time exposure to NP, matching profoundly with the pattern observed during acute virus infection. Furthermore, the effect of NP exposure on virus reactivation could also be observed in human cells latently infected with Epstein-Barr-Virus (EBV). Our results indicate that the combination of NP exposure and persistent herpesvirus infection restores a molecular signature found in acute virus infection, boosts production of lytic viral proteins, and induces an inflammatory response in the lung – a pattern which might finally result in tissue damage and fibrotic alterations.

ORGANISM(S): Mus musculus

PROVIDER: GSE79501 | GEO | 2016/12/19

SECONDARY ACCESSION(S): PRJNA316002

REPOSITORIES: GEO

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Nanoparticle exposure of persistently herpesvirus-infected cells reactivates latent virus and restores a signature observed during acute virus infection in vitro and in vivo

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