Research Horizons
Neutron scattering study yields new insights into virus life cycle.
Without a host, a virus is a dormant package of proteins, genetic material and occasional lipids. Once inside a living cell, however, a virus can latch onto cell parts and spring into action—mutating, replicating and spreading into new cells.
The mosquito-borne Sindbis virus is a member of the same family that causes West Nile fever and dengue fever. [Image credit: Paredes et al., Virology 324, 373 (2004)]
"There's this thought that a virus has one structure, whether it's in a mosquito or in a human cell," says ORNL researcher Flora Meilleur. "But a mosquito cell and a human cell are very different, which means that a virus may have to reorganize itself."
Meilleur is part of a research team from ORNL and North Carolina State University (NCSU) that is examining how viruses change their structure when they move among different host species. Understanding how a virus reorganizes itself when migrating from a mosquito to a human is essential for developing medicines that can block the spread of viruses.
The team's most recent study, published in the Journal of Virology, focuses on the Sindbis virus, a member of the arbovirus family that causes infectious diseases like yellow fever, dengue fever and West Nile fever. Scientists have previously observed host-specific differences in the Sindbis virus, but Meilleur says the team's study is the first time that subtle structural variations in Sindbis have been observed and characterized. "This is the first structural comparison of Sindbis viruses grown in different host cells."
The team, which includes Meilleur, Lilin He, Dean Myles and William Heller from ORNL and Amanda Piper, Raquel Hernandez and Dennis Brown from NCSU, used a technique called small-angle neutron scattering to compare virus particles from mammalian and insect cells. Their results revealed that the mammalian-grown viruses exhibited distinct features, including a larger diameter, increased levels of cholesterol and a different distribution of genetic material in the virus core. "The results suggest that structural changes are likely to be important in transmission between hosts," Meilleur says. "The chemical environment of the host cell appears to affect how the virus assembles itself."
The team's structural studies were performed at ORNL's High Flux Isotope Reactor using the facility's Bio-SANS instrument, which uses chilled neutrons to analyze the structure, function and dynamics of complex biological systems. Whereas techniques like X-ray scattering can cause radiation damage in biological samples during analysis, neutron scattering is nondestructive. "Neutron scattering enables us to see differences in the composition of the virus without destroying the sample," Meilleur says. The ability of neutrons to see the composition of biological materials is linked to the particles' sensitivity to hydrogen, which is a key component in compounds like proteins and cell membranes.
Although viral agents from the arbovirus family are a major source of human disease across the globe, very few effective vaccines exist for their control. A detailed understanding of the mechanism by which viruses gain entry into cells will be crucial for the successful pursuit of pharmaceuticals to ultimately treat and prevent infection from members of this virus family.