1a.Objectives (from AD-416):
The objective of this cooperative research project is to characterize field isolates of swine influenza A virus (SIV) for the purpose of utilizing this knowledge to develop improved prevention and control programs.
1b.Approach (from AD-416):
Swine flu is caused by SIV, and is one of the top 3 disease concerns for US pork producers. Influenza A viruses can change or mutate through 2 general mechanisms. The first one is known as antigenic drift, this a process by which the virus mutates at a slow rate that is dependent on how frequently there is a mistake in replicating the virus genome. This mistake results in random changes in the nucleic acid sequence. The second process is antigenic shift. The genome of influenza A viruses is composed of 8 segments. When 2 different flu viruses infect the same cell it is possible for one or more of these segments to be switched between the different viruses. This switching of gene segments between viruses is call antigenic shift and this process can account for rapid genetic changes. In addition to drift and shift, swine are susceptible to infection with avian and human influenza A viruses. This phenomenon also contributes to rapid genetic change for SIV.
The above described mechanisms for genetic change when coupled with modern swine husbandry make swine flu a dynamic disease. The potential for rapid genetic/antigenic changes has made this disease difficult to control through the use of commercial vaccines. In response, there is a growing trend to utilize autogenous vaccines, but they are not the complete answer.
The NADC swine influenza project has focused on improving vaccines by developing vectored and attenuated SIV vaccines; and by in vivo and in vitro characterization of SIV field isolates. This research program requires a team of scientific and technical staff. Due to the recent departure of skilled staff, it is necessary to develop a working relationship with others that have a molecular skill set working with negative-sense RNA viruses.
Thus the proposal for scientists from the NADC and ISU-CVM to collaborate on in vivo and in vitro characterization of SIV field isolates. The influenza A virus research will focus on studies that will. 1)characterize viruses at a genetic level,. 2)development a reverse genetics system, and. 3) use this reverse genetics system to study virus function.
This subordinate project is in support of Subobjective 2.1A, Monitor swine influenza virus (SIV) isolates from National Animal Health Laboratory Network (NAHLS) surveillance (USDA, APHIS) and other sources. The initial objective of this project was to develop a laboratory method that could be used to generate virus clones for the purpose of studying how they cause disease in swine. We determined that the regulation of the expression of one of the virus genes, the PB1-F2 gene is quite complicated. The regulation of PB1-F2 was presumed to be like a light switch, either on or off. However, a virus may have both "on" and "off" switches that are active in varying degrees so the regulation of the gene is more like a rheostat. This regulation process may be even more complicated since different isolates have their rheostat set at different levels. It is not clear at this time what ultimately regulates this novel phenomenon. The project ended 12/31/2011 and this information is being summarized to be published.