Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2006
Publication Date: 2/1/2007
Citation: Cauthen, A.N., Swayne, D.E., Sekellick, M.J., Marcus, P.I., Suarez, D.L. 2007. Amelioration of influenza pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene. Journal of Virology. 81(4):1838-1847.
Interpretive Summary: Avian influenza virus is occasionally found in commercial poultry where it can cause mild disease, referred to as low pathogenic avian influenza, or severe disease, referred to as highly pathogenic avian influenza. This paper describes the characterization of a low pathogenic avian influenza virus that was originally isolated from turkeys in the early 1970s and a variation of this virus that is missing part of the non-structural gene. The Nonstructural gene is known to aid the virus to bypass part of the chicken immune response by blocking the production of a chemical called interferon. Interferon helps limit the amount of virus produced when an animal is infected. This study showed the original virus could grow to higher levels and cause more disease than could the virus with the altered nonstructural gene. This difference between the viruses helps us understand how influenza viruses can cause disease in chickens which may lead to better ways to control influenza outbreaks in poultry.
Technical Abstract: Avian influenza virus A/TK/OR/71-SEPRL(H7N3) encodes a full length NS1 protein and is a weak inducer of interferon (IFN). A variant, TK/OR/71-delNS1(H7N3), produces a truncated NS1 protein and is a strong inducer of IFN. These otherwise genetically related variants differ 20-fold in their capacity to induce IFN in primary chicken embryo cells, but are similar in their sensitivity to the action of interferon (IFN). Furthermore, the weak IFN-inducing strain actively suppresses IFN induction in cells otherwise programmed to produce it. These phenotypic differences are attributed to the enhanced IFN-inducing capacity that characterizes AIV strains which produce defective NS1 protein. The pathogenesis of these two variants was evaluated in 1-day-old and 4-week-old chickens. The cell tropism of both viruses was similar. However, the lesions in chickens produced by the weak IFN-inducer were more severe and differed somewhat in character from those observed for the strong IFN-inducer. Differences in lesions included the nature of inflammation, rate of resolution of the infection, and the extent of viral replication and/or virus dissemination. The amelioration of pathogenesis is attributed to the higher levels of IFN produced by the variant encoding the truncated NS1 protein, and the antiviral state subsequently induced by that IFN. The high titer observed in kidney tissue (~10*9 ELD/gm) from 1-day-old chickens infected intravenously by the weak IFN-inducing strain is attributed to the capacity of chicken kidney cells to activate the HA fusion peptide along with their unresponsiveness to inducers of IFN as measured in vitro. Thus, the IFN-inducing capacity of AIV may be a significant factor in regulating the pathogenesis, virulence, and viral transmission of AIV in chickens. This suggests that the IFN-inducing and IFN induction-suppression phenotypes of AIV should be considered when characterizing strains of influenza virus for use in vaccines.