Key amino acid residues of neuraminidase involved in influenza A virus entry

Pathog Dis. 2019 Aug 1;77(6):ftz063. doi: 10.1093/femspd/ftz063.

Abstract

Generally, influenza virus neuraminidase (NA) plays a critical role in the release stage of influenza virus. Recently, it has been found that NA may promote influenza virus to access the target cells. However, the mechanism remain unclear. Here, we reported that peramivir indeed possessed anti-influenza A virus (IAV) activity in the stage of viral entry. Importantly, we verified the critical residues of influenza NA involved in the viral entry. As a result, peramivir as an efficient NA inhibitor could suppress the initiation of IAV infection. Furthermore, mutational analysis showed NA might be associated with viral entry via amino acids residues R118, E119, D151, R152, W178, I222, E227, E276, R292 and R371. Our results demonstrated NA must contain the key amino acid residues can involve in IAV entry.

Keywords: Influenza A virus; neuraminidase; neuraminidase active site; peramivir; viral entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids, Carbocyclic
  • Amino Acids / genetics*
  • Amino Acids / metabolism*
  • Animals
  • Antiviral Agents / pharmacology
  • Cyclopentanes / pharmacology
  • DNA Mutational Analysis
  • Dogs
  • Guanidines / pharmacology
  • HEK293 Cells
  • Humans
  • Influenza A virus / genetics*
  • Influenza A virus / physiology*
  • Madin Darby Canine Kidney Cells
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Neuraminidase / genetics*
  • Neuraminidase / metabolism*
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism*
  • Virus Internalization*

Substances

  • Acids, Carbocyclic
  • Amino Acids
  • Antiviral Agents
  • Cyclopentanes
  • Guanidines
  • Mutant Proteins
  • Viral Proteins
  • NA protein, influenza A virus
  • Neuraminidase
  • peramivir