New RSV images could reveal vulnerabilities in the resilient virus

New RSV images could reveal vulnerabilities in the resilient virus because the intricate structure of the respiratory syncytial virus (RSV) is a significant obstacle in developing treatments for an infection that hospitalizes or leads to worse outcomes for hundreds of thousands of people in the United States each year, according to the Centers for Disease Control and Prevention. Researchers at the University of Wisconsin-Madison have produced for preventing or slowing RSV infections.

DateOctober 1, 2024
SourceUniversity of Wisconsin-Madison
SummaryAccording to the Centers for Disease Control and Prevention, the intricate structure of respiratory syncytial virus (RSV) poses a significant challenge in developing effective treatments for an infection that causes hospitalizations and severe outcomes for hundreds of thousands in the U.S. annually. However new images of RSV may provide crucial insights into preventing or mitigating infections. RSV is particularly concerning for young children, the elderly, and adults.
New RSV images could reveal vulnerabilities in the resilient virus

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New RSV images could reveal vulnerabilities in the resilient virus

RSV is especially concerning for young children, the elderly, and adults at high risk for respiratory issues. Unlike other widespread respiratory illnesses, such as the flu, RSV has limited treatment options. In the U.S., preventive treatments are available for young children, and vaccines are approved only for pregnant women and the elderly. The virus’s structure, composed of small, flexible filaments, has made it difficult for researchers to identify key drug targets, particularly viral components shared across related viruses.

“There are several viruses related to RSV that are also significant human pathogens, including measles,” says Elizabeth Wright, a professor of biochemistry at UW-Madison. “Our knowledge of related viruses provides clues about RSV protein structures, but to identify drug targets, we need a closer examination of RSV proteins closely associated with host cell membranes.”

Wright’s team used cryo-electron tomography (cryo-ET), a cutting-edge imaging technique, to unveil key details of RSV’s molecules and structures. Their findings, recently published in Nature, offer important insights into the virus’s form and function.

New RSV images could reveal vulnerabilities in the resilient virus
New RSV images could reveal vulnerabilities in the resilient virus

Cryo-ET works by flash-freezing viral particles or molecules at extremely low temperatures, halting biological processes. This enables researchers to capture high-resolution images of cells, organelles, and viruses, essentially freezing them in time. By freezing multiple RSV particles, cryo-ET can visualize nearly all of the virus’s configurations from various angles. These 2D images are then combined to create detailed 3D representations, down to the atomic level.

The team’s study produced high-resolution images of two crucial RSV proteins: the RSV M protein and RSV F protein. Both play key roles in the virus’s interaction with host cells and are also found in related viruses.

The RSV M protein binds with the host cell membrane, maintaining the virus’s filamentous structure and coordinating its components, including the RSV F proteins. The F proteins, positioned on the virus’s surface, are responsible for engaging with host cell receptors, regulating the virus’s fusion and entry into the host cell. The images revealed that in RSV, two F proteins pair up to form a more stable unit, potentially preventing the virus from infecting the host prematurely.

“Our findings provide structural insights that help us understand not only how the protein regulates the assembly of viral particles but also how the coordination of these proteins enables the virus to become infectious,” says Wright.

The researchers believe that targeting these F protein pairs could be a potential strategy for destabilizing the virus before it infects its next host, paving the way for future drug development: Wright and her team plan to continue studying how RSV proteins interact to drive infection.

FAQ:

1. What is RSV?

Respiratory syncytial virus (RSV) is a common and contagious virus that causes respiratory infections. It primarily affects the lungs and breathing passages, often leading to mild cold-like symptoms but can result in more severe illness, especially in young children, the elderly, and those with weakened immune systems.

2. Who is most at risk for RSV?

RSV poses the greatest risk to:
Infants, particularly those under 6 months old
Premature babies
Older adults, especially those with underlying heart or lung conditions
Individuals with weakened immune systems
Adults with chronic respiratory conditions