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Viral infection

De-chaperoning antivirals

Nature Reviews Microbiology volume 14, pages 2–3 (2016)Cite this article

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Host chaperones from the Hsp70 ATPase family have a role in several stages of the life cycles of numerous viruses, including dengue virus (DENV), which currently has no approved antiviral therapy. However, despite the availability of Hsp70 inhibitors, their potential as antiviral therapeutics has not been explored. Now, two studies show that Hsp70 inhibitors are promising candidates as antivirals against flaviviruses, including DENV, and Kaposi's sarcoma-associated herpesvirus (KSHV).

To investigate the stages of the life cycle inhibited by JG40, the authors applied the drug at different time points during infection, which showed that Hsp70 is required for both viral entry and post-entry stages, including virion biogenesis. An examination of the effect of JG40 on individual DENV proteins showed that the capsid protein and the RNA-dependent RNA polymerase enzyme, known as NS5, are particularly reliant on Hsp70 activity for their stability; immunoprecipitation experiments confirmed that both proteins are direct substrates of Hsp70.

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References

  1. Taguwa, S. et al. Defining Hsp70 subnetworks in dengue virus replication reveals key vulnerability in flavivirus infection. Cell 163, 1108–1123 (2015)

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  2. Baquero-Pérez, B. & Whitehouse A. Hsp70 isoforms are essential for the formation of Kaposi's sarcoma-associated herpesvirus replication and transcription compartments. PLoS Pathog. 11, e1005274 (2015)

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Authors
  1. Naomi Attar
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Attar, N. De-chaperoning antivirals. Nat Rev Microbiol 14, 2–3 (2016). https://doi.org/10.1038/nrmicro.2015.12

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