Will VP35 be Ebola’s weak link?

ResearchBlogging.orgEbola is a viral disease that only occasionally infects humans, but when it does, he fatality rate is very high. In some population, where culturally determined methods of treating the dead involve a lot of contact with bodily fluids and where people are unaware of techniques to avoid spread of infection and are otherwise at risk, a large percentage of a rural village population can become infected, and the survival rate once infected can be as low as 10%. With increased awareness of how to avoid infection and even the most basic improvements in patient care, these numbers can be much improved, but fatality rates have never been lower than about 25% and are usually closer to 50%.

(Part of the large variation in survival rate data comes form the fact that ebola outbreaks always involve relatively small numbers of people and are rare. Useful rate data are best obtained from much larger samples.)

The protein VP35 is one of a small number of molecules that make up the center of the virus. VP35 serves several functions. Together with nearby proteins, VP35 is involved in ‘reproduction,’ such as it is for viruses. But VP35 also inhibits interferon, an immune system product, in the infected (host) individual. It turns out that mutations that affect this protein also mess up the virus’s ability to avoid the interferon.

A paper just coming out in the Proceedings of the National Academy of Sciences explores the physical structure of VP35 at several levels, allowing for a characterization of the protein, with the hope of leading to the development of an effective anti-viral treatment.

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From the paper:

Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists.

D. W. Leung, N. D. Ginder, D. B. Fulton, J. Nix, C. F. Basler, R. B. Honzatko, G. K. Amarasinghe (2009). Structure of the Ebola VP35 interferon inhibitory domain Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0807854106

Comments

  1. #1 minas
    January 5, 2009

    really interesting!!

  2. #2 LZ
    April 10, 2009

    Interesting Post. Updating the news, now we have the full lenght recombinant protein, expressed and purified in a bacterial system. Such model will allow us biochemical in vitro assays to develop antiviral VP35 inhibitors for its several fucntions. Look at “Zinzula et al. 2009″ on pubmed.com. Cheers.