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Title: Characterization of influenza virus variants with different sizes of the non-structural (NS) genes and their potential as live influenza vaccine in poultry

Author
item WANG, L - OHIO STATE UNIVERSITY
item Suarez, David
item Pantin Jackwood, Mary
item MIBAYASHI, M - MT SINAI SCHOOL OF MEDICI
item GARCIA-SASTRE, A - MT SINAI SCHOOL OF MEDICI
item SAIF, Y - OHIO STATE UNIVERSITY
item LEE, C-W - OHIO STATE UNIVERSITY

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2008
Publication Date: 6/22/2008
Citation: Wang, L., Suarez, D.L., Pantin Jackwood, M.J., Mibayashi, M., Garcia-Sastre, A., Saif, Y.M., Lee, C. 2008. Characterization of influenza virus variants with different sizes of the non-structural (NS) genes and their potential as live influenza vaccine in poultry. Vaccine. 26:3580-3586.

Interpretive Summary: Avian influenza virus can present a serious disease threat to poultry, and new approaches for disease control are needed. In an attempt to better understand the virus, studies were conducted on an unusual viral variant that has a defective viral gene called the nonstructural protein 1 (NS1). This protein is known to be important to the virus by helping overcome the defenses of the host, particularly the interferon response. The variant virus has a small deletion of its genetic material that allows only half the protein to be produced. The change does not appear to be stable, because in further studies, other variants appeared with different sized NS1 proteins. Because the virus has a defective NS1 protein, it appears to have reduced ability to cause disease in poultry. This attenuation of the virus could allow the virus to be used a live vaccine for use in poultry, and preliminary studies show promising results. Further work is necessary to see if a live vaccine using these attenuated viruses provide good protection at a low enough cost to be used commercially.

Technical Abstract: The influenza virus isolate A/turkey/Oregon/71-delNS1 (H7N3) has a 10 nucleotide deletion in the coding region of the NS1 gene and as a result produces a truncated NS1 protein. From a stock of this virus, we found that several variants with different sizes of the NS genes exist. The number of variants with different sizes of the NS gene were selectively increased during the passage in 10- and 14-day-old embryonating chicken eggs (ECE), but not in 7-day-old ECE or Vero cells. Using reverse genetics, we confirmed that NS genes of different sizes could arise directly from the parental A/turkey/Oregon/71-delNS1 NS sequence. The selected NS genes with different size of deletions appeared to be genetically stable. These observations demonstrate unique compensatory adaptation processes of the influenza virus with the defective NS genes. Further analysis of NS gene variants with different sizes of deletion in different locations of the NS gene will provide more insights on the function of specific parts of the NS gene. Furthermore, in vivo studies with plaque purified NS variants shows that naturally selected NS deletion variants can be useful in the development of live attenuated influenza vaccines in poultry.