A groundbreaking study may finally explain why a scientific community capable of splitting the atom, sequencing genomes, and putting people on the moon has not yet discovered a cure for the common cold. Using sophisticated three-dimensional imaging technology, researchers have created a detailed structural model of rhinovirus C – one of the most common causes of the illness. Analyses of the model suggest that previously unknown differences in the virus’ protein coat allow the infection to evade all current therapies.
Past research has implicated two related pathogens in common cold infections: rhinovirus A and rhinovirus B. In 2006, researchers studying the illness stumbled across a third agent, which was later dubbed rhinovirus C. Virtually all cases of common cold are thought to be the result of one of these three infections. Many theorized that this new viral strain was the “missing link” needed to develop effective treatments against the infection that sickens countless people each year. Essentially, the third strain offered an explanation why therapies in clinical trials didn't yield consistent outcomes.
The new study, which is forthcoming in the journal Virology, sought to determine why rhinovirus C consistently evades drugs that otherwise elicit responses in rhinovirus A and B infections. To do this, the researchers constructed a three-dimensional model of the pathogen’s viral capsid – the spherical protein shell that allows the virus particle to invade the body, hijack a cell, and deposit its nucleic acid. According to co-author Ann Palmenberg, the model revealed a number of remarkably different features.
“The question we sought to answer was how is it different and what can we do about it? We found it is indeed quite different,” Palmenberg explained in a press release. She added that the new structure “explains most of the previous failures of drug trials against rhinovirus.”
To construct the model, the Palmenberg and her colleagues collected information from 500 rhinovirus C genomes using genetic sequencing – an analytic tool that allows researchers to review an organism’s entire genetic framework. The precise coordinates derived from the data was subsequently used to generate a three-dimensional image in computer program. “It’s a very high-resolution model,” Palmenberg said. “We can see that it fits the data.”
Hopefully, the research effort is not all bad news. With the structure in hand, future projects may be able to develop new drug mechanisms that work across all three rhinoviruses. “[Rhinovirus C] has a different receptor and a different receptor-binding platform,” the researchers wrote. “Because it’s different, we have to go after it in a different way.”
Source: Holly A. Basta, Jean-Yves Sgro, Ann C. Palmenberg. Modeling of the human rhinovirus C capsid suggests a novel topography with insights on receptor preference and immunogenicity. Virology, 2014; 448: 176