Novel virus entry mechanism could lead to new drugs against poxviruses

Scientists working with Vaccinia virus, the smallpox vaccine, have discovered a novel mechanism that allows poxviruses to enter cells and cause infection.

Research published in the Proceedings of the National Academy of Sciences describes how the Imperial College London team discovered the mechanism allowing Vaccinia virus to shed its outer lipid membrane and enter cells. The mechanism is unique in virology and paves the way for development of new antiviral drugs.

Many viruses, such as influenza, are surrounded by a single lipid membrane, or envelope, and to enter cells this membrane must be removed. Previously, all enveloped viruses were thought to shed their lipid membrane by fusion with a cell membrane which allows the virus 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 researchers found that interactions between polyanionic or negatively charged molecules on the cell surface and glycoproteins on the virus particle caused a non-fusogenic disruption of the virus outer envelope, allowing the poxvirus to enter the cell.

As well as discovering how the double membrane problem is solved, the researchers demonstrated that polyionic compounds can be used to treat poxvirus infections, 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.

Professor Geoffrey L. Smith FRS, from Imperial College London and a Wellcome Trust Principal Research Fellow, said: “This work has uncovered a completely novel biological process. 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.”

The research team included Mansun Law, Gemma C. Carter, Kim L. Roberts, Michael Hollinshead and Geoffrey L. Smith.

The researchers have filed a patent for this discovery with Imperial Innovations, the College’s spin out arm.