Replication-competent influenza A viruses expressing a red fluorescent protein

Virology. 2015 Feb:476:206-216. doi: 10.1016/j.virol.2014.12.006. Epub 2014 Dec 30.

Abstract

Like most animal viruses, studying influenza A in model systems requires secondary methodologies to identify infected cells. To circumvent this requirement, we describe the generation of replication-competent influenza A red fluorescent viruses. These influenza A viruses encode mCherry fused to the viral non-structural 1 (NS1) protein and display comparable growth kinetics to wild-type viruses in vitro. Infection of cells with influenza A mCherry viruses was neutralized with monoclonal antibodies and inhibited with antivirals to levels similar to wild-type virus. Influenza A mCherry viruses were also able to lethally infect mice, and strikingly, dose- and time-dependent kinetics of viral replication were monitored in whole excised mouse lungs using an in vivo imaging system (IVIS). By eliminating the need for secondary labeling of infected cells, influenza A mCherry viruses provide an ideal tool in the ongoing struggle to better characterize the virus and identify new therapeutics against influenza A viral infections.

Keywords: 2A; Antivirals; In vivo imaging system (IVIS); Influenza A virus; Interferon; Microneutralization assay; NS1; Neutralizing antibodies; Replication-competent virus; Virus neutralization assay; mCherry.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Tracking / methods*
  • Female
  • Gene Expression
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A virus / genetics
  • Influenza A virus / physiology*
  • Influenza, Human / virology*
  • Luminescent Proteins / genetics*
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Red Fluorescent Protein
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication*

Substances

  • INS1 protein, influenza virus
  • Luminescent Proteins
  • Viral Nonstructural Proteins