While monkeypox has been circulating in Africa for many years, the recent outbreak across the world has revealed considerable uncertainty about virus transmission. People infected with the monkeypox virus usually recover from the disease on their own without medical treatment, but the questions raised reinforce the need for research to understand how the virus spreads and causes disease, which is essential for the development of new vaccines and therapeutics.
Suresh Kuchipudi, Huck Chair in Emerging Infectious Diseases at Penn State, and his colleagues, including nine members of his lab, hope to answer these and other questions in a new study aimed at identifying the potential for reverse zoonoses. – when viruses circulating in humans spill over to animals — with monkey pox. Additionally, the team will study virus pathogenesis – or disease development – in animal and human cells in vitro (in a test tube), as well as potential targets for therapeutics to treat monkeypox disease. These areas have also been identified as US monkeypox research priorities by the White House.
“Domestic animals like cattle are susceptible to other smallpox viruses, but their susceptibility to monkeypox and their role in spreading the virus are unclear. Therefore, we plan to take a first step towards understanding the ability of monkeypox to replicate in the respiratory cells of cattle and pigs in a controlled in vitro [in a test tube] environment and use computer models to predict susceptibility,” Kuchipudi said, noting that the research will not be conducted in vivo and no animals will be used in this research. “If we find that the virus can replicate in the cells of cattle, this suggests the possibility that the virus could spread in these animals and become endemic in the United States”
As acting director of Penn State’s Animal Diagnostics Laboratory, Kuchipudi already has extensive experience studying zoonotic diseases – or diseases that can be transmitted between species – including other smallpox diseases, such as goat pox and sheep pox, and more recently COVID-19 in livestock and wildlife, including white-tailed deer.
According to Kuchipudi, although much less transmissible than SARS-CoV-2, monkeypox is known to be transmitted between animals through close contact with broken skin or bodily fluids. Among humans, although not fully known, it is possible that the virus is also transmitted through respiratory droplets, potentially playing a critical role in secondary transmission after the primary dermal route. However, once the virus enters the body, its pathogenesis is not well understood.
“Most research on monkeypox is decades old,” Kuchipudi said. “Our goal is to fill this gap by studying the pathogenesis of monkeypox in human cells and identifying targets for therapeutic development. We currently know of two different strains of the virus that have been detected in the United States, and our work will use the less virulent strain, which is from West Africa.”
According to the CDC, although vaccines are available, there are currently no specific approved treatments for monkeypox virus infections; however, antivirals developed for use in patients with smallpox may prove beneficial. In collaboration with Marco Archetti, Associate Professor of Biology, the researchers will explore a new post-infection therapeutic – a synthetic therapy based on defective interfering particles (DI) for monkeypox. Archetti has previously designed and demonstrated the efficacy of a synthetic DI therapy for COVID-19.
“A defective synthetic virus is a harmless version of a real virus that interferes with the growth of the real virus,” Archetti said. “These defective viruses are like parasites of the real virus. Eventually, they bring about the extinction of both the pathogenic virus and themselves.”
Lora Weiss, senior vice president for research, Penn State, noted that the COVID-19 pandemic has highlighted the need to expand our study and understanding of zoonotic diseases.
“For a variety of reasons, we are increasingly aware of zoonotic diseases in the United States, and our researchers are at the forefront of studying these diseases to better understand emerging pathogens that may affect human health,” she said. “We believe that scientific research like this will not only inform public health, but is also essential to advancing scientific knowledge, allowing us to develop treatments before disease emerges.”
This research will be performed at the Eva J. Pell BSL-3 Enhanced Laboratory for Advanced Biological Research, a secure biocontainment facility built and operated to criteria mandated by the National Institutes of Health, USDA, and State Centers for Disease Control United States, which was built to enable Penn State scientists to conduct research into infectious diseases and pathogens. The researchers have obtained the necessary regulatory approvals and follow all protocols and safety procedures required by the federal government and the university to conduct this type of research. All team members are fully trained and have received the appropriate approvals to work with infectious disease agents.
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