A flexible “viral dial” helps hepatitis C virus escape antibodies and control cell entry

What is it about?

Hepatitis C virus (HCV) is very good at escaping the immune system. One reason is a highly variable and immunodominant stretch in its virus surface antigen, called hypervariable region 1 (HVR1). We used a virus neutralizing antibody to study HVR1’s structure and how it is displayed on the viral antigen with X-ray crystallography and electron microscopy, and to test how it affects antibody neutralization and receptor binding. Our results show that HVR1 stays flexible even when antibodies are bound, and that it can shield conserved sites on the virus from neutralizing antibodies while also influencing how the virus engages its cell receptors. We propose the term “viral dial” to describe the behavior of this virus element, which may let the virus adapt to its environment, such as the host immune response, to survive.

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Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Why is it important?

HVR1 is both highly flexible and a main target of the immune response, which makes it a challenge for HCV vaccine design. We found that anti-HVR1 antibody can weaken the effect of neutralizing antibodies that target conserved parts of the virus . The antibody can also alter the virus’s preference of binding to different cell receptors. These findings show that the immunodominant antibodies against HVR1 can interfere with cross-neutralizing antibodies, which should be addressed when designing a HCV vaccine.

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