Correlating: Flavivirus virulence and levels of intrinsic disorder in shell proteins: Protective roles vs. immune evasion

Gerard Kian Meng Goh, A. Keith Dunker, Vladimir N. Uversky

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (CFRs) among Flaviviruses and within at least two Flavivirus species, such as tick-borne encephalitis virus (TBEV) and dengue virus (DENV). The shell proteins analyzed in this study are capsid (C) and membrane (PrM, Pr, and M) proteins. The highest correlations can be found when regression analyses were conducted using Pr (Flavivirus: r2 = 0.78, p < 0.01) or M (Flavivirus: r2 = 0.91, p < 0.01) as an independent variable with C and CFR as co-explanatory and dependent variables, respectively. Interestingly, while predicted intrinsic disorder levels (PIDs) of both C and M are positively correlated with the virulence, the PIDs of Pr and CFR are negatively correlated. This is likely due to the fact that the Pr portion of PrM plays various roles in protecting the virion from damage, whereas M and C are assisted by greater potential in binding promiscuity as a result of greater disorder. The C protein of yellow fever virus (YFV), which is the most virulent virus in the sample, has the highest PID levels, whereas the second most virulent TBEV FE subtype has the second highest PID score due to its C protein, and the least virulent West Nile virus (WNV) has the least disordered C protein. This knowledge can be used while working on the development and identification of attenuated strains for vaccine. Curiously, unlike Flaviviruses, a disordered outer shell was described for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human simplex virus 2 (HSV-2), which currently have no effective vaccine.

Original languageEnglish (US)
Pages (from-to)1881-1891
Number of pages11
JournalMolecular BioSystems
Volume12
Issue number6
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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