Viruses are commonly classified as enveloped or non-enveloped, but a new study of hepatitis A suggests that this classic distinction may be overly simplistic (Nature 496, 367–371).

Credit: Chris Bjornberg / Science Source

Hepatitis A virus (HAV) is a non-enveloped RNA virus that causes enterically transmitted hepatitis. Now, Stanley Lemon and his colleagues show that a high percentage of HAV particles released from cultured liver cells are enveloped in a host-derived membrane. Circulating infectious virus of the same density as the enveloped form was also present in blood from HAV-infected humans and chimpanzees. Mechanistically, the authors found that the host endosomal-sorting complexes required for transport (ESCRT) proteins VPS4B and ALIX were needed for assembly of the enveloped HAV particles.

Notably, a neutralizing monoclonal antibody was unable to neutralize the enveloped form of HAV, suggesting that the virus might use this strategy to evade the host immune response. Passive transfer of antibodies can protect infected patients from disease after viral replication is well-established in the liver, and the authors found that antibodies targeted against the viral capsid could restrict replication of the enveloped virus in hepatocyte cultures even when the antibodies were applied several hours after infection. However, it is currently unclear how these effects are mediated, and this will need to be resolved in future studies.