The C-terminal helical domain of dengue virus precursor membrane protein is involved in virus assembly and entry

Virology. 2011 Feb 5;410(1):170-80. doi: 10.1016/j.virol.2010.11.006. Epub 2010 Dec 3.


The role of the α-helical domain (MH) of dengue virus (DENV) precursor membrane protein in replication was investigated by site-directed mutagenesis. Proline substitutions of three residues (120, 123 and 127) at the C-terminus, but not those at the N-terminus of MH domain, reduced the virus-like particles of DENV1, DENV2 and DENV4 detected in supernatants. In a DENV2 replicon trans-packaging system, these three mutations suppressed particles detected; two of them (I123P and V127P) also affected viral entry. In the context of DENV2 genome-length RNA, all three mutations reduced virion assembly and virus spreading in cell culture. Analysis of revertants showed that mutation A120P could partially support viral infection cycle; in contrast, mutations I123P and V127P were lethal, and adaptations of I123P→I123L and V127P→V127L were required to restore the viral infection cycle. These findings demonstrate that the C-terminus of the MH domain is involved in both assembly and entry of DENV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cricetinae
  • Dengue Virus / genetics
  • Dengue Virus / metabolism*
  • Gene Expression Regulation, Viral / physiology
  • Humans
  • Mice
  • Mutation
  • Protein Precursors / chemistry
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Protein Structure, Tertiary
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*
  • Virus Assembly / physiology*
  • Virus Internalization*


  • Protein Precursors
  • Viral Matrix Proteins