KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA
2009

Pim-1 and Pim-3 Kinases are Essential for KSHV Reactivation

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Author Information

Author(s): Cheng Fang, Weidner-Glunde Magdalena, Varjosalo Markku, Rainio Eeva-Marja, Lehtonen Anne, Schulz Thomas F., Koskinen Päivi J., Taipale Jussi, Ojala Päivi M.

Primary Institution: University of Helsinki, Finland

Hypothesis

Pim-1 and Pim-3 kinases are required for the reactivation of Kaposi's sarcoma herpesvirus (KSHV) from latency.

Conclusion

Pim-1 and Pim-3 kinases are critical regulators of KSHV reactivation by phosphorylating the latency-associated nuclear antigen (LANA), which counteracts its repression of viral gene transcription.

Supporting Evidence

  • Pim-1 and Pim-3 were shown to be up-regulated during KSHV reactivation.
  • Phosphorylation of LANA by Pim-1 and Pim-3 counteracts its ability to inhibit viral gene transcription.
  • Silencing Pim-1 or Pim-3 significantly reduced KSHV reactivation.
  • IFN-γ treatment increased Pim-1 levels and induced KSHV reactivation.

Takeaway

This study found that two proteins, Pim-1 and Pim-3, help a virus called KSHV wake up from sleep mode so it can make more copies of itself.

Methodology

The study used a gain-of-function screen to identify kinases that induce KSHV reactivation and performed various assays to analyze the role of Pim kinases in this process.

Limitations

The study primarily focused on specific cell lines and may not fully represent KSHV behavior in all biological contexts.

Digital Object Identifier (DOI)

10.1371/journal.ppat.1000324

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