title: Sequence signatures in envelope protein may determine whether flaviviruses produce hemorrhagic or encephalitic syndromes.
abstract: We analyzed the envelope proteins in pathogenic flaviviruses to determine whether there are sequence signatures associated with the tendency of viruses to produce hemorrhagic disease (H-viruses) or encephalitis (E-viruses). We found that, at the position corresponding to the glycosylated Asn-67 in dengue virus, asparagine (Asn) occurs in all seven viral species that cause hemorrhagic disease in humans. Furthermore, Asn was extremely rare at position 67 in six flaviviruses that cause encephalitis, being replaced by Asp in four of them. Of the 3,246 sequences from H- and E-viruses, we found that 2,916 sequences (90%) contained Asn in position 67 for H-viruses or Asp in position 67 for E-viruses. The change from Asn-67 that is prevalent in H-viruses to Asp-67 (common in E-viruses) contributes to a stronger electrostatically negative surface in the E-viruses as compared to the H-viruses. These findings should help predicting the disease potential of emerging and re-emerging flaviviruses and understanding the relationship between protein structure and disease outcome.
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: Winona C
authors.initials: WC
authors.lastname: Barker
authors.forename: Raja
authors.initials: R
authors.lastname: Mazumder
authors.forename: Sona
authors.initials: S
authors.lastname: Vasudevan
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Sagripanti
authors.forename: Cathy H
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D018792:Encephalitis, Viral / Q000821:virology; D005416:Flavivirus / Q000235:genetics* / Q000472:pathogenicity*; D006470:Hemorrhage / Q000821:virology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D014759:Viral Envelope Proteins; D037521:Virulence Factors; D001224:Aspartic Acid; D001216:Asparagine