Master of Philosophy The University of Hong Kong, Hong Kong
Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness mostly seen in infants and children under the age of five. Enterovirus A71 (EV-A71) is one of the causative agents of HFMD. While most cases of EV-A71 infection are mild and self-limiting, some can progress to severe neurological complications, including aseptic meningitis, brainstem encephalitis and acute flaccid paralysis, which makes EV-A71 infection a serious public health problem. The progression of EV-A71 infection is typically characterized by an initial fever, followed by the development of painful oral ulcers, a rash on the hands and feet, and in severe cases, neurological symptoms. The precise molecular mechanisms underlying the pathogenesis of EV-A71 are not fully understood, but several factors have been implicated in disease severity. Although several EV-A71 vaccines have been developed and are currently available in China and other countries, additional research is still needed to further enhance our understanding of EV-A71 virology and to develop more effective therapeutics and vaccines.
AMP-activated protein kinase (AMPK) is a key energy sensor that regulates energy homeostasis in response to the changes in cellular environment. It is a serine/threonine kinase that is activated by an increase in the intracellular AMP/ATP ratio, which indicates cellular energy depletion. Research findings highlight the potential of targeting AMPK as a therapeutic strategy for various diseases, including cancer, metabolic disorders, cardiovascular disease, and neurodegenerative diseases. In addition to its metabolic functions, AMPK has been shown to play an important role in viral infection in recent studies.
Our preliminary study has shown that EV-A71 may induce AMPK activation during infection, which may be a strategy of host immune response or requirement of viral infection. The AMPK agonists AICAR and metformin showed significant effects on the suppression of EV-A71 replication. However, the underlying mechanism is still unknown. Enterocytes derived from human pluripotent stem cells will be hired to investigate if AMPK activation participates in EV-A71 infection. Our research findings will be a new antiviral strategy used in developing new drugs and vaccines for HFMD.
