Human Parainfluenza Virus Type 3 Matrix Protein Reduces Viral RNA Synthesis of HPIV3 by Regulating Inclusion Body Formation

Viruses. 2018 Mar 11;10(3):125. doi: 10.3390/v10030125.

Abstract

Human parainfluenza virus type 3 is one of the main causes of lower respiratory illness in newborns and infants. The role of the matrix protein (M) in viral budding is extensively studied, but the effect of M on viral replication remains to be determined. Using an HPIV3 minigenome assay, we found that M reduced HPIV3 mingenome-encoded reporter activity even though it had an unspecific effect on the expression of cellular genes. Furthermore, the inhibition effect of M on viral RNA synthesis was proven to be independent of its virus-like particles (VLPs)' release ability. A VLP's defective mutant (ML302A) decreased the expression of minigenome reporter as wild type M did. Using an immunofluorescence assay, we found that M weakened the formation of inclusion bodies (IBs), although it did not co-localize with the IBs. Moreover, using another mutant, ML305A , which is defective in M-nucleoprotein (N) interaction, we found that ML305A had no effect on reporter activity and IB formation as the wild type of M did. Taken together, we conclude that M reduces the replication of HPIV3 and IB formation by M-N interaction.

Keywords: M–N interaction; human parainfluenza virus type 3; inclusion body formation; viral replication; virus-like particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Viral
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Inclusion Bodies, Viral*
  • Mutation
  • Parainfluenza Virus 3, Human / physiology*
  • Protein Binding
  • RNA, Viral / biosynthesis*
  • Respirovirus Infections / virology*
  • Transcription, Genetic
  • Viral Matrix Proteins / metabolism*
  • Viral Proteins
  • Virus Assembly
  • Virus Release
  • Virus Replication

Substances

  • RNA, Viral
  • Viral Matrix Proteins
  • Viral Proteins