Browsing by Subject "Avian Influenza"
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Item An Integrated Study of Avian Influenza Impacts and Associated Climate Change Issues(2012-07-16) Mu, JianhongThis dissertation examines issues related to avian influenza (AI) disease. This is done via three essays that individually examine: (1) the impacts of climate change on the probability and expected numbers of AI outbreaks and associated economic loss; (2) the effects that media coverage of AI outbreaks has on meat demand in the United States, and (3) the potential effectiveness of AI mitigation strategies on poultry production and welfare under a simulated AI outbreak in United States. The climate change and spread of AI outbreaks study finds that the probability and expected number of AI outbreaks increases as climate change proceeds. Particularly, past climate change has contributed to the current spread of AI disease by 11% and the future climate change will increase this spread by another 12%. Moreover, the underreporting probability of AI outbreaks is also examined and results show that the underreporting probability is much higher in countries with lower gross domestic production level, larger export of poultry products and more numbers of AI confirmed human deaths. Therefore, disease prevention and control plans should focus on these economically poor and climatically changed regions. AI outbreak information has significant effects on meat demand in the United States. In particular, impacts of overseas AI human deaths on meat demand equal 0.02% for beef, -0.005% for pork, and -0.01% for chicken for sample when there was no AI occurred in the United States, while it has smaller impacts on meat expenditure when using the whole sample. In addition, human deaths due to AI disease will increase beef demand and decrease that for pork and chicken. However, AI media coverage in short-run has insignificant effect on meat demand, which suggests that consumers are more cautious when cases occur within the United States as opposed to international cases. In the study on the effects and welfare implications of AI mitigation strategies, results find that vaccination strategy is welfare decreasing under most cases of demand shocks but is desirable in some regions when both domestic and excess demand decrease. Under the assumption of one AI outbreak in the United States, the associated mitigation costs because of past climate change are relatively small.Item Role and Importance of NS1 Protein of Avian Influenza Virus to Grow in the Presence of Interferon and Evaluation of the NS1 Mutant Viruses as Potential DIVA Vaccines(2010-10-12) Brahmakshatriya, VinayakA proper vaccination program can play a critical role in prevention and control of avian influenza (AI) in commercial poultry. Low pathogenic avian influenza viruses (LPAIV) of H5 and H7 AI subtypes cause serious economic losses to the poultry industry and have the potential to mutate to highly pathogenic AI (HPAI) strains. Due to trade implications, differentiation of infected from vaccinated animals (DIVA) is an important issue in the control of AI. Therefore, the development and characterization of vaccine candidates with DIVA properties is critical in improving vaccination programs. Keeping these aspects in mind, we investigated the role of an NS1 mutant virus as a potential live attenuated DIVA vaccine. The NS1 protein of influenza virus plays a major role in blocking the host's antiviral response. Using an eight-plasmid reverse genetics system, we recovered the low pathogenic parental (H5N3) and NS1 mutant (H5N3/NS1/144) viruses. H5N3/NS1/144 expresses only the first 144 amino acids of the NS1 protein compared to the 230 of the parental H5N3. The growth properties of H5N3 and H5N3/NS1/144 were compared in cell culture and in different age embryonated chicken eggs. Our results confirmed that NS1 is involved in down regulation of interferon as shown by IFN-beta mRNA expression analysis and by the inability of H5N3/NS1-144 to efficiently grow in older age, interferon competent, chicken embryos. However with regards to safety the virus reverted to virulence within five back passages in chickens and was therefore not a safe vaccine candidate. However the killed form of H5N3/NS1-144 was a safer alternative and it also induced antibody titers and protection not significantly different from the parental H5N3 as vaccine. To further understand the reversion of H5N3/NS1/144 to virulence, we carried out 3 independent serial passages of H5N3/NS1/144 in increasing age of embryonated chicken eggs and examined the NS1 gene for presence of mutations. RT-PCR and sequence analysis of the NS gene in all three lineages showed the presence of a 54 amino acid deletion resulting in the generation of a 87 amino acids long NS1 ORF with a point mutation (L80V) at the site of deletion. In addition, the NS1 ORF in lineages L2 and L3 presented two additional point mutations in the RNA binding domain (Q40R and T73M). To determine if these mutations played a role in increased virulence, recombinant viruses expressing these mutant NS1 proteins in the background of parental virus were generated by reverse genetics and their replication properties and pathogenicity was examined in vitro, in ovo and in vivo systems. Our results showed that the 87 amino acid long NS1 protein clearly increased virus replication and virulence specifically in interferon competent systems. In addition, the two point mutations in the RNA binding domain of NS1 ORF expressing 87 a protein slightly increased the virus virulence. Overall this study reinforces the role of NS1 in influenza virus pathogenicity and supports the use of killed inactivated NS1 mutant virus vaccines as potential DIVA vaccines.