Geoffrey Smith of Imperial College London and colleagues have discovered how Vaccinia, the smallpox vaccine, enters cells and causes infection. The findings shed light on a novel mechanism by which active pox viruses can infect people. Apparently, the Vaccinia virus sheds its outer lipid membrane to enter cells. This naked entrance mechanism is unique in virology and could pave the way for a range of new antiviral drugs.
Many viruses, such as the H5N1 avian influenza virus, are surrounded by a single lipid membrane, or envelope. To enter cells this membrane has to be shed. Previously, all enveloped viruses were thought to shed their lipid membrane by fusion with a cell membrane which allows the viral core to be released into the cell.
In contrast, the extracellular form of Vaccinia virus has two lipid membranes, meaning a single fusion event will not release a naked virus core into the cell. The Imperial team has found that interactions between negatively charged molecules on the cell surface and sugar-linked proteins, glycoproteins, on the virus’ surface split the virus outer envelope without fusing, allowing the poxvirus to enter the cell.
As well as discovering how the double membrane problem is solved, the researchers demonstrated that these multiply charged, polyionic, compounds can destroy the poxvirus even days after infection has started. Disrupting the outer membrane with polyanionic compounds exposes the virus, allowing antiviral antibodies to be more effective. The disruption of the outer membrane also limits the spread of the virus in the body.
“This work has uncovered a completely novel biological process,” Smith, “It increases our understanding of how viruses can manipulate biological membranes and will help the development of new drugs against poxviruses, such as variola virus, the cause of smallpox.”
Details in Proc Nat Acad Sci