Related Experiment Video

Updated: Feb 23, 2026

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
22:10

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

Published on: June 28, 2013

13.7K

Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702

Alex W H Chin1, Nathaniel K C Leong1, John M Nicholls2

  • 1Centre of Influenza Research & School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Scientific Reports
|September 14, 2017
PubMed

Insights

Influenza virus PB2 polymerase mutations at positions 701-702 reveal high sequence plasticity. These changes impact viral polymerase activity, replication, and pathogenicity in mammals and birds.

Area of Science:

  • Virology
  • Molecular Biology
  • Protein Engineering

Background:

  • The PB2 polymerase subunit of influenza viruses is crucial for viral replication.
  • Positions 701 and 702 of PB2 are implicated in host range determination.
  • Limited natural variation at these sites restricts functional studies.

Purpose of the Study:

  • To investigate the functional impact of diverse amino acid substitutions at positions 701 and 702 of the influenza PB2 polymerase.
  • To explore the relationship between sequence changes, polymerase activity, and viral phenotypes in different hosts.

Main Methods:

  • Random mutagenesis was employed to generate 31 viable influenza viruses with mutations at PB2 positions 701-702.
  • In vitro assays were used to measure polymerase activity and viral replication rates in mammalian and avian cells.
  • In silico analysis predicted surface electrostatic charges on the PB2 structural model.
  • Pathogenicity and tissue tropism were assessed in mouse models and chicken embryos.

Main Results:

  • The PB2 701-702 positions tolerate a wide range of amino acid substitutions, generating viable viruses.
  • Mutants exhibited varied polymerase activities and replication kinetics in different cell types.
  • Increased positive surface electrostatic charge in this region correlated with enhanced polymerase activity in mammalian cells.
  • One mutant (701A/702E) showed reduced pathogenicity in mice, while others were similar to wild-type.
  • Distinct tissue tropisms were observed for PB2 mutants in chicken embryos.

Conclusions:

  • The PB2 701-702 region possesses significant sequence plasticity, allowing for diverse amino acid substitutions.
  • Alterations in this region can modulate influenza virus polymerase function, replication efficiency, and pathogenicity.
  • These findings provide insights into influenza virus adaptation and host tropism.

More Related Videos

Production of High-Titer Infectious Influenza Pseudotyped Particles with Envelope Glycoproteins from Highly Pathogenic H5N1 and Avian H7N9 Viruses08:10

Production of High-Titer Infectious Influenza Pseudotyped Particles with Envelope Glycoproteins from Highly Pathogenic H5N1 and Avian H7N9 Viruses

Published on: January 15, 2020

8.9K
Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies07:55

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

Published on: August 29, 2017

12.3K

Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
1.0K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
40.0K