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Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion

Siritorn Butrapet1, Thomas Childers, Kelley J Moss

  • 1Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.

Virology
|March 1, 2011
PubMed

Insights

Mutations in the dengue virus envelope protein

Area of Science:

  • Virology
  • Molecular Biology
  • Infectious Diseases

Background:

  • The dengue virus envelope (E) protein is crucial for viral entry and infection.
  • Specific regions, like the molecular hinge, are vital for E protein function.
  • Understanding these regions can reveal targets for antiviral strategies.

Purpose of the Study:

  • To identify amino acids (AAs) in the dengue virus E protein's molecular hinge critical for viral infection.
  • To elucidate the roles of specific hinge residues in viral infectivity, fusion, and replication.

Main Methods:

  • Engineering of fifteen mutant dengue viruses with specific amino acid substitutions in the E protein hinge.
  • Assessment of viral infectivity in mammalian cells.
  • Determination of the pH threshold for viral fusion.
  • Evaluation of viral replication in both mammalian and mosquito cell lines (C6/36).
  • Sequence analysis to identify potential compensatory mutations and interactions between residues.

Main Results:

  • Substitutions at Q52, A54, and E133 reduced mammalian cell infectivity and altered fusion pH.
  • Mutations at F193, G266, I270, and G281 impacted replication in both cell types; I270W showed reduced fusion.
  • T280Y affected fusion pH and C6/36 cell replication.
  • L135 mutations were lethal in mammalian cells; L135G abrogated fusion but had minimal impact on mosquito infection rates.
  • L135W replicated well in C6/36 cells but had the lowest mosquito infection rate.
  • Sequence analysis suggested interactions between hinge residues (e.g., 52 and 277, or 53, 135, 170, 186, 265, and 276).

Conclusions:

  • Specific amino acids in the dengue virus E protein hinge are essential for infectivity, fusion, and replication.
  • Mutations in the hinge region can differentially affect mammalian and mosquito cell infectivity and transmission.
  • Identified interactions suggest a complex functional network within the E protein hinge.

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