Researchers designed experiments using gene-editing tools to discover how molecules called gangliosides serve as de facto gatekeepers to allow the virus entry into liver cells and trigger disease.
The research, published in Nature Microbiology, has revealed gangliosides as a key player in HAV and has led to several other questions, such as how exactly viral RNA transitions between different compartments in human liver cells to replicate and cause disease.
«Discovering that gangliosides are essential receptors for HAV infection adds an interesting plot twist to the hepatitis A story,» said senior author Stanley Lemon, MD, professor of medicine and microbiology at the UNC School of Medicine and member of the UNC Institute for Global Health and Infectious Diseases. «Gangliosides are structurally similar across mammalian species, unlike proteins, which helps explain cross-species transmission of ancient hepatoviruses. Understanding what helps a virus jump from one animal species to another is incredibly important, as evidenced so plainly by the current Covid-19 pandemic.»
HAV was discovered nearly 50 years ago, and although there is a vaccine, there is no treatment. The virus still infects more than 1.4 million people globally each year, and in recent years has been causing increasing numbers of hepatitis cases in the United States, some fatal. Many people experience very mild or no symptoms, especially children. Patients with symptoms, which can last eight weeks and sometimes longer, often experience nausea, vomiting, diarrhea, jaundice, fever, and abdominal pain. After initial infection, 10 to 15 percent of infected individuals experience a recurrence of symptoms during the first six months. Acute liver failure is rare, but more common in elderly people.
HAV infects people through mechanisms similar to other viruses; it interacts with receptor molecules on the surface of human cells to gain entry. Knowing the receptor for a virus not only helps researchers understand how the virus enters cells, but also creates opportunities to design antivirals to block the interaction to prevent or treat disease.
Among the five known hepatitis viruses that cause acute or chronic liver disease in humans, receptors have been identified for hepatitis C virus and hepatitis B virus. For hepatitis A, the identity of the receptor remained elusive. The black sheep of the picornavirus family, it uniquely exists in two modes: as nonenveloped (naked) viruses (nHAV), comprised of a protein shell called a capsid surrounding an RNA genome; or as ‘quasi-enveloped’ viruses (eHAV), in which capsids containing the viral genome are cloaked inside host cell membranes.
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Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.