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Published on: November 4, 2015
Parainfluenza virus entry at the onset of infection
Tara C Marcink1, Matteo Porotto2, Anne Moscona3
1Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States; Center for Host-Pathogen Interaction, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
Insights
Parainfluenza viruses cause severe respiratory infections in children. This study details how these viruses fuse with cells, offering potential targets for antiviral therapies.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Parainfluenza viruses (PIV) are a major cause of lower respiratory tract infections in children worldwide.
- PIV are enveloped viruses belonging to the Paramyxoviridae family, known for their negative-sense, single-stranded RNA genome.
- Viral entry into host cells is mediated by the fusion of the viral envelope with the cell membrane.
Purpose of the Study:
- To elucidate the mechanism of cell entry mediated by the PIV fusion complex.
- To understand the coordinated action of the viral receptor binding protein (RBP) and fusion protein (FP).
- To identify potential strategies for blocking viral fusion and inhibiting infection.
Main Methods:
- Structural biology approaches were utilized to examine the PIV fusion process.
- Analysis focused on the molecular interactions between the RBP and FP during viral entry.
- Studies were conducted on the surface of viral particles to observe fusion dynamics.
Main Results:
- The PIV RBP forms a stable complex with the FP until receptor binding occurs.
- Receptor binding triggers the FP to undergo conformational changes, leading to membrane fusion.
- The structural transitions of the fusion machinery were characterized.
Conclusions:
- Understanding the molecular mechanism of PIV-mediated membrane fusion is crucial for developing antiviral strategies.
- Targeting the coordinated action of the RBP and FP presents a viable approach to inhibit PIV infection.
- Further research into the structural dynamics of viral entry can lead to novel therapeutic interventions.
Abstract:
Parainfluenza viruses, members of the enveloped, negative-sense, single stranded RNA Paramyxoviridae family, impact global child health as the cause of significant lower respiratory tract infections. Parainfluenza viruses enter cells by fusing directly at the cell surface membrane. How this fusion occurs via the coordinated efforts of the two molecules that comprise the viral surface fusion complex, and how these efforts may be blocked, are the subjects of this chapter. The receptor binding protein of parainfluenza forms a complex with the fusion protein of the virus, remaining stably associated until a receptor is reached. At that point, the receptor binding protein actively triggers the fusion protein to undergo a series of transitions that ultimately lead to membrane fusion and viral entry. In recent years it has become possible to examine this remarkable process on the surface of viral particles and to begin to understand the steps in the transition of this molecular machine, using a structural biology approach. Understanding the steps in entry leads to several possible strategies to prevent fusion and inhibit infection.
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