piperidines and Influenza-in-Birds

Chicken interferon-alpha (ChIFN-α) has been demonstrated to be an important cytokine in antiviral immunity. However, the preventive or therapeutic effect of ChIFN-α as an oral antiviral agent on avian influenza virus (AIV) infection has not been fully clarified in chickens systemically. In the present study, we investigated the anti-H9N2 AIV effect of ChIFN-α on a cohort of 7- and 33-day-old specific pathogen-free (SPF) chickens by oral administration. Results showed that both the ChIFN-α preventive and therapeutic groups exhibited significantly reduced viral load in trachea when compared with the virus-challenged control group. The therapeutic effect was better than the preventive effect on 7-day-old SPF chickens, which is opposite to 33-day-old SPF chickens. We speculated that T-dependent lymphocyte system of 33-day-old SPF chickens might be easier to be stimulated by ChIFN-α than that of 7-day-old SPF chickens. In addition, there was no side effect on the body weight of chickens treated with ChIFN-α. We also found that IFN-stimulated genes (ISGs) (2',5'-oligoadenylate synthetase and Mx1) were upregulated in groups treated by ChIFN-α and/or virus, indicating that these 2 ISGs not only participated in anti-AIV response in vivo but also could be induced by oral administration of ChIFN-α. The present study suggested that ChIFN-α could be used as a potential preventive and therapeutic antiviral agent against H9N2 AIV infection by oral administration.

Topics: 2',5'-Oligoadenylate Synthetase; Administration, Oral; Animals; Antiviral Agents; Chickens; Drug Combinations; Gene Expression Regulation, Viral; Immunization; Influenza A Virus, H9N2 Subtype; Influenza in Birds; Interferon-alpha; Organometallic Compounds; Piperidines; Recombinant Proteins; Trachea; Virus Replication

Norakin-resistant (NR) mutants of fowl plague virus (A/FPV/Weybridge, H7N7) have 1 to 2 (in one instance 3) amino acid substitutions in different positions of the heavy (HA 1) and/or light (HA 2) subunits of the haemagglutinin (HA) molecule. Investigation of NR mutants using the haemagglutination inhibition test with monoclonal antibodies (MAb) to the HA of A/seal/Massachusetts/80 (H7N7) virus revealed that one of the mutants (NR 1) differs antigenically from the wild-type fowl plague virus: its haemagglutination was not inhibited by MAb 55/2 and 58/6. By contrast, MAb-resistant (escape) mutants, selected from the wild-type fowl plague virus under pressure from MAb 55/2 or 58/6, showed reduced drug sensitivity. These findings suggest a possibility of correlation between alteration of influenza virus antigenicity and change of its sensitivity to drugs whose target is the haemagglutinin. This potential effect should be taken into account when antiviral substances directed to surface influenza virus antigens are being developed for use as antiviral drugs.

Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Birds; Chick Embryo; Drug Resistance, Microbial; Epitopes; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Influenza A virus; Influenza in Birds; Molecular Sequence Data; Mutation; Piperidines