The intricate structure of respiratory syncytial virus (RSV) poses a significant challenge in creating effective treatments for this infection, which annually sends hundreds of thousands of individuals in the United States to hospitals, as reported by the Centers for Disease Control and Prevention. Recent findings from researchers at the University of Wisconsin-Madison may offer insights into ways to prevent or diminish RSV infections. This virus predominantly affects young children, elderly individuals, and adults with heightened vulnerability to respiratory issues.
The complicated structure of respiratory syncytial virus creates obstacles in developing treatments for an infection responsible for hospitalizations or worse for hundreds of thousands of people in the U.S. every year, according to the CDC. Recent images of the virus captured by researchers at the University of Wisconsin-Madison could provide crucial information for preventing or moderating RSV infections.
The highest risk groups for RSV include young children, older adults, and individuals at high risk for respiratory issues. Unlike influenza and other common respiratory infections that circulate in schools every year, treatment options for RSV remain limited. In the U.S., preventative treatments exist for young children, while current vaccines are only available for pregnant women and the elderly.
The virus’s convoluted structure, comprising tiny, flexible filaments, has proven elusive to researchers. This complex shape has hindered the identification of essential drug targets, including viral parts that are shared among similar viruses.
“There are several viruses related to RSV that are also important human pathogens, such as measles,” notes Elizabeth Wright, a biochemistry professor at UW-Madison. “Our understanding of related viruses helps us deduce information about RSV protein structures, but to pinpoint drug targets, we need a closer examination of RSV proteins that closely interact with host cell membranes.”
Employing an imaging method known as cryo-electron tomography (cryo-ET), Wright and her research team have successfully detailed key molecules and structures vital for the form and function of RSV. Their recent findings were published in Nature.
Cryo-ET involves freezing viral particles or other molecules at extremely low temperatures, halting biological processes mid-action. This allows researchers to study the structures of various organisms, cells, organelles, and viruses, capturing minute images of these structures suspended in time. When numerous RSV particles are flash-frozen, cryo-ET imaging can capture nearly all possible configurations of the virus from multiple perspectives. These two-dimensional images can then be synthesized to create a high-resolution representation of the virus’s three-dimensional structures, revealing details down to the level of individual atoms.
Wright’s latest research produced high-resolution images highlighting the structures of two crucial RSV proteins, the M protein and the F protein, both of which play essential roles in how the virus interacts with the membranes of host cells. These proteins are also found in related viruses.
The RSV M protein engages with host cell membranes, maintaining the virus’s filamentous structure and coordinating its components, including the RSV F proteins. The F proteins, located on the surface of the virus, are prepared to interact with host cell receptors and facilitate the virus’s fusion and entry into the host cell. The visual data obtained reveals that in RSV, two F proteins come together to create a more stable entity. Wright suggests that this connection may inhibit the F proteins from prematurely infecting the host cell.
“Our key findings unveil structural details that enhance our understanding of how the protein regulates the assembly of viral particles, as well as the interaction of proteins that allow the virus to remain infectious,” states Wright.
The researchers speculate that the pairing of F proteins could be vital for destabilizing the virus before it becomes capable of causing infection, making these protein pairs a promising focus for future drug development. They plan to continue investigating how RSV proteins interact to facilitate infection.
