Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus.

Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Research Abstract Details 

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Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Abstract Text:

Natalia A Ilyushina,Elena A Govorkova,Charles J Russell,Erich Hoffmann,Robert G Webster,

In the present study we determined the antiviral effect of amantadine against influenza A/Netherlands/219/03 (H7N7) virus in cell culture and in a mouse model. Amantadine at concentrations <100 muM failed to inhibit virus replication in Madin-Darby canine kidney (MDCK) cells. When orally administered to mice for 5 days, amantadine at 15 mg kg(-1) day(-1) did not protect animals against lethal challenge with H7N7 infection, and virus titres in mouse organs were not reduced. However, sequence analysis of the M2 protein revealed none of the mutations previously described as being associated with amantadine resistance. We used reverse genetics to generate viruses containing the haemagglutinin (HA) or M gene of A/Netherlands/219/03 virus to investigate the role of these genes in amantadine sensitivity. All recombinant viruses carrying the HA segment of A/Netherlands/219/03 (H7N7) virus were amantadine-resistant, regardless of the origin of their other genes. To study the role of fusion activity in the mechanism of drug resistance, we introduced the Gly(23)-->Cys mutation in the H7 fusion peptide. This substitution resulted in a decrease of the pH of fusion and was also associated with reduced virus replication in both MDCK cells and mice, as compared to that of the wild-type virus. We suggest that H7 HA protein plays a role in amantadine resistance, although all HA amino acids that participate in drug resistance still remain to be characterized. Our finding reveals that sequence analysis of the transmembrane domain of M2 protein may not adequately identify all drug-resistant variants.

Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Publishing Authors By Initials

NA Ilyushina,EA Govorkova,CJ Russell,E Hoffmann,RG Webster,

For similar proteins: viral proteins: viral structural proteins: viral envelope proteins: viral matrix proteins research abstracts see: proteins: viral proteins: viral structural proteins: viral envelope proteins: viral matrix proteins research

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MEDLINE DATE:

Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of general virology

VOLUME: 88

Page Numbers: 1266-74

Journal Abbreviation: J. Gen. Virol.

ISSN: 0022-1317

DAY: 3

MONTH: Apr

YEAR: 2007

Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 77340

Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Keywords Mesh Terms:

KEYWORDS: Viral Matrix Proteins

MESH TERMS: physiology

Chemical & Substance for Abstract: Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. Information

Substance Name: Amantadine

Registry Number: 768-94-5

Grant and Affiliation Information for Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus.

AFFILIATION: Division of Virology, Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Country: England

AGENCY: United States NCI

GRANT: CA-21756

ACRONYM: CA

MEDLINETA: J Gen Virol

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