This project will carry out surveillance in swine in collaboration with a major pork production facility to investigate the natural history of influenza in swine. Our studies will determine the prevalence of swine influenza virus (SIV) and reassorted influenza viruses in swine that in close contact with humans, and investigate how these viruses evolve, reassort, adapt, transmit and cause disease. We will determine the molecular, ecologic and host factors that influence the evolution, emergence, transmission and pathogenicity of influenza viruses allowing for the rational design of intervention strategies for agriculture and public health to block the emergence and spread of zoonotic influenza.
Animal influenza surveillance in Guangxi, China
Chinalai Yang, PhD, Hualan Chen, PhD
The focus of this project is to carry out influenza virus surveillance in farm animals including chickens, ducks and swine to test the hypothesis that the geographic conditions and farming practices in Guangxi may facilitate interspecies transmission of influenza viruses among domestic animal populations. The objectives of this study are to determine prevalence of different influenza viruses in these animal species, to determine antigenic, pathogenic, as well as transmissibility changes of these viruses over time, to investigate the frequency of influenza virus cross-species transmission, and to gain an in depth understanding of the effect of poultry influenza vaccination on virus evolution and inter- or intra-species spread. These results will enhance our knowledge of the epidemiology of animal influenza virus, and provide guidance for improving and better implementing public health and veterinary health policies for preventing or mitigating new influenza outbreaks and pandemics.
Influenza glycoprotein functions as determinants of host range, transmission, pathogenicity and pandemic potential
The project will investigate how basic receptor binding and membrane fusion functions of the influenza hemagglutinin glycoprotein (HA) influence the biology of virus replication, host range, and potential for emergence in humans, as well as the mechanisms by which we might design broadly effective vaccines. The objectives of the study are to identify natural receptors for influenza viruses and their distribution in human tissues; characterize the receptor destroying properties of the neuraminidase (NA) protein, and determine how this balances with HA binding activity; and define the mechanism of action and range of specificity for the virus neutralization properties of anti-HA stem antibodies, which often display much broader specificity than HA head domain antibodies commonly induced by normal infection or standard vaccination.
Interplay among host adaptation, reassortment and transmission of influenza viruses at the animal-human interface
This project will elucidate the evolutionary processes that facilitate growth and transmission of animal influenza viruses in human hosts. Knowledge of the mechanisms by which influenza viruses at the animal-human interface overcome the human species barrier is critical to our ability to identify strains with zoonotic or pandemic potential and to understand the conditions under which such viruses are likely to emerge. The objectives of the study are to evaluate reassortment of swine and human influenza viruses; identify and characterize low fitness intermediates in the evolution of influenza viruses; and evaluate the impact of adaptation of avian influenza viruses to human cells on the potential for reassortment with human viruses and transmission among mammals.
Human Immune Responses to influenza vaccination and infection
This project has two primary objectives: first, to understand the interplay between innate and adaptive immunity using a systems biological approach; and second, to provide insight into the mechanisms that regulate the duration of humoral immunity to influenza virus. These studies will provide key information towards the development of a “universal influenza vaccine,” a vaccine that could protect us not only from past and current influenza strains but perhaps also against any pandemic strains that may emerge in the future. In addition, the enhanced susceptibility of pregnant women to influenza with significant consequences to her developing fetus (i.e., low birth weight and prematurity) places a great premium on vaccinating this special population, and the CDC and WHO have highlighted this as one of the major issues of public health importance.