Small RNAs growing tall: miRNAs as drug targets in herpesvirus infections

L’Hernault, Anne; Dölken, Lars

doi:10.1016/j.coviro.2015.07.010

Cited by 2 publications

(2 citation statements)

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“…In particular, it has been proposed that ncRNAs directly or indirectly contribute to the maintenance of latency, either by targeting pivotal viral lytic genes or by targeting cellular regulatory pathways used to control latency1619205354. For gammaherpesviruses, this has been shown for KSHV where viral miRNAs help to maintain latency by mediating the repression of RTA (replication and transcription activator) or by targeting the NF-kB pathway, and it has also been shown for EBV where viral miRNAs help to maintain latency by targeting BALF5 (the EBV DNA polymerase) or by targeting Dicer (see references 12, 18, 19, 53, 54, 55 for recent reviews). The studies with KSHV and EBV have all been performed in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Besides the identification of potential targets of a herpesviral miRNA, the demonstration of its biological function, preferentially in the context of viral infection, is needed to finally define its role in infection and pathogenesis11. Using various model systems combined with reverse genetics approaches, important roles for herpesviral ncRNAs in the viral life cycle and in pathogenesis have been described, including the regulation of viral persistence, host cell proliferation, long-term survival of host cells and immune evasion (reviewed, for example, in111213141516171819202122). However, the biological functions have so far largely been explored in in vitro systems whereas the respective knowledge during infection in vivo is still very limited.…”

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confidence: 99%

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The small noncoding RNAs (sncRNAs) of murine gammaherpesvirus 68 (MHV-68) are involved in regulating the latent-to-lytic switch in vivo

Steer

Strehle

Christine

et al. 2016

Sci Rep

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The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), which are associated with a variety of diseases including tumors, produce various small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs). Like all herpesviruses, they show two stages in their life cycle: lytic replication and latency. During latency, hardly any viral proteins are expressed to avoid recognition by the immune system. Thus, sncRNAs might be exploited since they are less likely to be recognized. Specifically, it has been proposed that sncRNAs might contribute to the maintenance of latency. This has already been shown in vitro, but the respective evidence in vivo is very limited. A natural model system to explore this question in vivo is infection of mice with murine gammaherpesvirus 68 (MHV-68). We used this model to analyze a MHV-68 mutant lacking the expression of all miRNAs. In the absence of the miRNAs, we observed a higher viral genomic load during late latency in the spleens of mice. We propose that this is due to a disturbed regulation of the latent-to-lytic switch, altering the balance between latent and lytic infection. Hence, we provide for the first time evidence that gammaherpesvirus sncRNAs contribute to the maintenance of latency in vivo.

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