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Susceptibility of influenza A viruses to amantadine is influenced by the gene coding for M protein
Abstract:
Influenza A virus recombinants derived from "resistant" and "sensitive" parental viruses were examined for susceptibility to inhibition by amantadine. Correlation of gene constellation and amantadine susceptibility revealed that the gene coding for M protein influences sensitivity or resistance to amantadine. All recombinants which derived an M protein from an amantadine-resistant parent were found to be resistant to amantadine. All amantadine-sensitive recombinants derived an M gene from the amantadine-sensitive parent. However, a few amantadine-resistant recombinants which derived an M gene from the sensitive parent were also isolated, suggesting that the expression of amantadine sensitivity in these recombinants may be influenced by other genes.
Insights
The M protein gene in influenza A virus directly influences amantadine resistance. Reassortment studies show that the M protein is key to amantadine susceptibility, though other genes may also play a role.
Area of Science:
- Virology
- Molecular Biology
- Antiviral Drug Resistance
Background:
- Influenza A virus is a significant human pathogen.
- Amantadine has been used to treat influenza, but resistance is a concern.
- Understanding the genetic basis of amantadine resistance is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the genetic determinants of amantadine susceptibility in influenza A virus.
- To identify specific viral genes responsible for resistance or sensitivity to amantadine.
Main Methods:
- Generation of influenza A virus recombinants from amantadine-resistant and -sensitive parent strains.
- Assay of amantadine susceptibility in the resulting viral recombinants.
- Correlation of gene constellation with observed amantadine susceptibility phenotypes.
Main Results:
- The gene encoding the M protein was found to be a primary determinant of amantadine susceptibility.
- Recombinants possessing the M protein gene from resistant parents exhibited resistance.
- Recombinants with the M gene from sensitive parents were sensitive, with some exceptions suggesting other genetic influences.
Conclusions:
- The M protein plays a critical role in mediating amantadine resistance in influenza A virus.
- While the M gene is a major factor, other viral genes may modulate the expression of amantadine sensitivity.
- These findings contribute to understanding influenza A virus antiviral resistance mechanisms.