David Busath is a Brigham Young University biophysicist who wants to understand extremely small parts of the influenza A virus so that future research can identify better ways to keep it from reproducing. But he faces one "tiny" challenge: the parts are so minute that they cannot be seen with an electron microscope, so he and his collaborators at Florida State University used a 16-ton magnet to give the virus what amounts to an MRI.
Busath and his fellow researchers are zeroing in on a protein hole in the virus membrane, or skin, that governs what gets in and out of the virus. Since this channel is key to the influenza virus's ability to reproduce, and therefore infect people, the research lays an important foundation for improving anti-viral drugs. The team's results were published in a recent issue of the prestigious[Italics, Proceedings of the National Academy of Sciences].
The channel Busath is studying, dubbed M2 because it was the second protein discovered in the virus thought to be associated with the virus membrane, is blocked by a common anti-influenza drug, amantadine. Tamiflu, another anti-flu drug, is being stockpiled by governments around the world in preparation for a possible avian flu epidemic. Tamiflu works by blocking neuraminidase, a different protein in the virus membrane. A better understanding of viral channels and other viral proteins will aid efforts to develop better drugs.
"This line of research will have a large implication for knowing how selective these channels are," said Busath. "That will have implications for how the virus can survive, and maybe how we can kill it. We need other drugs so that if the virus mutates and becomes immune to one, we can attack it with another."
Busath, who taught at Brown University for 11 years before coming to BYU in 1995, also noted that the study has additional significance as a foundation for other viral research. For example, HIV has a channel similar to the one studied for this paper, and findings may be relevant to that deadly virus as well.
To study the tiny virus channel, the researchers transplanted it into samples that re-created its natural environment and then used very powerful magnetic fields to examine the protein structure. Doing so required Florida State's 15-foot tall magnet, which is housed at the National High Magnetic Field Laboratory and supervised by Timothy A. Cross, a Florida State researcher who is the senior author of the paper.
The magnet allows the team to use a technique called nuclear magnetic resonance – the underlying technology of an MRI – to map the structure of the channel. The huge size of Cross' magnet allows the team to make extremely precise readings of the distance between two molecules or atoms.
The main finding of the paper was that key components of the channel in the flu virus are closer together than previously thought, which is important in understanding how the channel decides whether the virus can distribute its genes into host cells and reproduce.
Busath runs special tests to ensure that the samples being studied behave in the same way as viruses in real cells, demonstrating that the experimental conditions have preserved the study's relevance to the real world.
Busath and Cross' work is funded by a five-year, multi-million dollar grant from the National Institutes of Health. Other authors on the paper include Viksita Vijayvergiya, a former postdoctoral fellow at BYU, and FSU's Jun Hu, Riqiang Fu, Katsuyuki Nishimura, Li Zhang, and Huan-Xiang Zhou.