Researchers have determined the structure of the rubella virus capsid protein, which is central to the virus's ability to assemble into an infectious particle and to infect humans.
Although a successful vaccine is available to protect against rubella virus infection, the discovery could aid efforts to develop vaccines and antiviral drugs to treat related infections.
The protein is located on the virus's inner portion of its shell, or capsid, and is an essential structural component as well as a key factor in virus-host interactions. The new findings reveal a protein structure not previously seen in other viruses that is an essential component of infectious rubella virus, said Michael Rossmann, Purdue Univ.'s Hanley Distinguished Prof. of Biological Sciences.
He led a team of researchers at Purdue that discovered the structure, working with researchers at the Univ. of Alberta who created mutated forms of the virus to validate the structural interpretation.
"What we predicted based on the structure is that if we mutated the virus to change the amino acids in a specific region it would destroy the virus and it wouldn't assemble," said Purdue doctoral student Vidya Mangala-Prasad, who graduates this semester.
The findings were published in the Proceedings of the National Academy of Sciences. The paper was authored by Mangala-Prasad; Univ. of Alberta graduate student Steven D. Willows; Purdue research scientist Andrei Fokine; Purdue postdoctoral researchers Anthony J. Battisti, Siyang Sun and Pavel Plevka; Tom Hobman, a prof. in the Dept. of Cell Biology at the Univ. of Alberta; and Rossmann.
"These studies may facilitate future vaccine design as well as aid in development of drugs for other RNA viruses for which there are no therapeutic treatments," Hobman said.
RNA viruses include those that cause SARS, influenza or hepatitis C.
The researchers used techniques called cryoelectron tomography, x-ray crystallography and multiple wavelength anomalous dispersion (MAD). Mangala-Prasad crystallized the protein and then used MAD to determine the structure.
"One challenge we had is that the structure we found is not similar to any of the known structures," she said. "So we didn't have any model to go by to solve this particular structure."
Rubella infection leads to severe damage in fetuses when contracted during pregnancy. It is in a class of viruses called togaviruses and causes "German measles," a relatively mild disease characterized by rashes and low-grade fever.
Source: Purdue Univ.