WASHINGTON, June 28 (Xinhua) -- American scientists have directly visualized in real-time structural changes in the surface protein of the influenza virus, showing that a protein on the virus could unfold to stretch toward target cells, and then refold and try again 5 to 10 times per second.
The study published on Thursday in the journal Cell revealed the flu virus to be more dynamic than previously thought and may help efforts to develop more effective vaccines and better understand other viruses such as Ebola, HIV, and SARS.
According to researchers at Tufts University School of Medicine, the envelope protein on the surface of viruses like flu must attach the virus to the cell membrane, and then fuse the virus and the cell.
Fusion allows release of the virus contents into the cell, so it can take over the cell's internal functions and replicate. Influenza's envelope protein hemagglutinin (HA) has long been a template for fusion mechanisms in other viruses.
"Envelope proteins have been described as old-fashioned mousetraps, set in a static, spring-loaded state, waiting to be triggered by interaction with a target cell," said the study's senior author James Munro, assistant professor of molecular biology and microbiology at Tufts School of Medicine.
"This process hadn't been directly observed, and it was widely thought that each protein molecule on the surface of the virus had only one chance to spring its trap," said Munro.
Using advanced imaging technology that can measure nanoscale distances within single molecules labeled with fluorescent dyes, the researchers generated the first real-time visualization of the changing shape of individual HA molecules seeking cellular targets.
"The fact that this viral molecule can reconfigure itself, then reverse that configuration and rapidly repeat that sequence multiple times changes the way we think about virus entry," said Munro.
Reversibility may potentially benefit the virus in several ways, including preventing early activation in the absence of an appropriate target, enabling virus molecules to synchronize their efforts to increase efficiency, and confusing a cell's protective antibodies, which must recognize the shape of a virus in order to defend against it, according to the study.
"Surface proteins are the only part of the virus that the immune system 'sees.' As a result, nearly all known antibodies that inhibit virus replication target these proteins," said Munro.
