The Keystone Symposia’s annual meeting on HIV Vaccines, held jointly this year with a meeting on Viral Immunity and Host Gene Influence, kicked off March 21 in Keystone, Colorado, with a keynote about hepatitis A and hepatitis C that could well have been entitled, “A Tale of Two Viruses.”
Stanley Lemon, a professor in the division of infectious diseases at the University of North Carolina whose research focuses on the molecular pathogenesis of hepatitis C, said the differences between the viral infections, which both largely impact the liver, are well known, starting with the fact that they belong to different single-strand RNA viral families. Hepatitis A is a non-enveloped picornavirus while hepatitis C is an enveloped flavivirus. The differences abound. Hepatitis A is acute and vaccine-preventable. Hepatitis C is chronic and there is no effective vaccine to prevent it. Hepatitis A causes mild symptoms and infected individuals develop lifelong immunity. Hepatitis C is asymptomatic but over time causes liver scarring, cirrhosis, and often liver failure. It is also very difficult to treat. “In the past two years, hepatitis C has been causing a greater number of deaths than HIV in the US,” said Lemon to the 400 scientists attending this conference.
Once a vaccine for hepatitis A was developed, said Lemon, research languished. But in recent years, his laboratory and others have taken a fresh look at the virus thinking that if they understood better how the human immune system controls hepatitis A it might lead to a better perspective on hepatitis C. Along the way they have encountered some unexpected twists, including surprising animal data from chimpanzees that found despite the rapid acute course of hepatitis A, viral RNA persisted for up to 50 weeks.
Both hepatitis A and hepatitis C are known to disrupt molecular signals that induce interferons and other proteins that help limit viral infection, though hepatitis C likely has developed other escape mechanisms that allow it to persist, said Lemon.
Lemon said more recent studies conducted in chimpanzees with acute infection found that hepatitis C evoked much more robust interferon-stimulated gene expression (ISG), while hepatitis A induced only minimal interferon-stimulated gene expression despite 100-fold more RNA in the liver. Lemon’s lab thought the lower levels of ISG expression during acute hepatitis A might be because plasmoid dendritic cells—innate immune cells that produce high amounts of interferon alpha—were unable to sense hepatitis A infection. But in fact their findings found that these dendritic cells were producing substantial quantities of interferon-alpha when co-cultured with hepatitis A, which require direct contact between the dendritic cells and cells infected with hepatitis A.
The second keynote address was given by Joseph Sodroski, associate director at Harvard Medical School’s Center for AIDS Research, who described ongoing work by his lab in elucidating the structure of HIV’s Envelope trimer, which recently has involved the use of cryo-electron microscopy using single-particle analysis.
Sodroski is in high demand these days. He was asked to give a plenary on the same subject March 7 at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) (see IAVI Report March 7 blog,
HIV’s Envelope Trimer, Up Close and Personal).
