Since 2013, more than 1,500 cases of bird-to-human transmission of Asian lineage H7N9 low-pathogenic avian influenza virus have been documented, resulting in 615 human deaths. Although H7N9 is not currently transmitted among humans, there exists potential for the virus to evolve in new directions. Researchers at Penn State have received a grant from the National Institute of Allergy and Infectious Diseases to study H7N9 with a goal of developing new and fundamental knowledge of virus mutations that could indicate the potential for transmissibility in humans.
“The COVID-19 pandemic has demonstrated the need for research that can help us anticipate new virus strains and how they may emerge,” said Troy Sutton, assistant professor of veterinary and biomedical sciences and the lead principal investigator on the grant. “Yet, we currently have limited ability to identify variants with the potential for increased transmission.”
According to the U.S. Centers for Disease Control and Prevention, “While the current risk to the public’s health posed by Asian H7N9 virus is low, the pandemic potential of this virus is concerning.” In this new project, Sutton and his laboratory group at Penn State will introduce mutations into a weakened vaccine-version of the H7N9 virus that replicates poorly in humans and is unlikely to transmit between people.
“Our team will use these viruses to infect cells in petri dishes,” said Sutton. “Specifically, we will infect human airway epithelial cells – such as from the nose, which is the first point of contact for the H7N9 wild-type virus to infect a human – in vitro. We can then determine if the mutations have the potential to enhance the virus’ infection of these cells as an indicator of the potential for infection and transmission in humans.”
Andrew Read, director of the Huck Institutes of the Life Sciences, added, “Working with a vaccine strain is safer than working with the wild-type virus because it has a decreased ability to infect humans and cause diseases. Carefully introducing mutations to viruses that have a very low chance of spread within the confines of a highly secure laboratory can help us to understand the biology of how these viruses can change to infect humans and potentially spread between people. As we begin to better understand the science, the goal is to better prepare for pandemics that may already be brewing in nature and ultimately protect our health and avoid significant adverse social and economic impacts of lockdowns.”
Sandeep Prabhu, head of the Department of Veterinary and Biomedical Sciences, noted that if the research team finds that the recombinant H7N9 viruses do indeed enhance infection of human airway epithelial cells in petri dishes, then public health officials will know what to look for in H7N9 viruses recovered from poultry and can take critical and immediate action.
“Information from such studies could be useful to global surveillance strategies because it could help in the identification of high-risk genetic sequences in emerging viruses,” said Prabhu. “For example, in response, poultry harboring these viruses can be quarantined or culled to limit the potential for transmission to humans. In addition, this information also may be used to select viruses for the subsequent generation of pandemic vaccine seed stocks and to evaluate if existing antiviral medications could be used to treat these viruses.”
By funding this project, the NIH believes in the importance of studying viruses with the potential to become pandemic. To receive funding from the NIH to conduct this research, Sutton’s proposal underwent a rigorous safety review process carried out by the National Institute of Allergy and Infectious Disease and the Department of Health and Human Services.
“Researchers are continually trying to identify the impacts of genetic changes; for example, scientists may modify bacteria to allow production of human insulin, or they may alter the genetics of corn plants so they are resistant to herbicides,” said Lora Weiss, senior vice president for research, Penn State. “Similarly, by seeking to understand the effects of other virus mutations, scientists may be able to help inform public health decisions. Dr. Sutton and his team are highly trained scientists with experience conducting this type of research. We are a strong research university that is continually conducting research to serve the greater good.”
This research will be performed at the Eva J. Pell BSL3 Enhanced Laboratory for Advanced Biological Research, a secure bio-containment facility built and operated under criteria mandated by the National Institutes of Health, the U.S. Department of Agriculture and the U.S. Centers for Disease Control. No animals will be used in this research.