Unveiling the Potential of a Single Amino Acid Change in Human Parainfluenza Virus Type 1
In a significant development in virology and pharmaceutical research, a study published in the Biological & Pharmaceutical Bulletin has shed new light on the mechanisms underpinning the infectivity of Human Parainfluenza Virus Type 1 (hPIV1). The study, conducted by a team from the University of Shizuoka, Japan, has uncovered a single amino acid substitution in the fusion glycoprotein of hPIV1 that remarkably enhances the virus’s capability to form syncytia and propagate within the host.
The Critical Role of Fusion Glycoprotein in hPIV1
hPIV1 is equipped with two spike glycoproteins integral to the virus’s life cycle: the hemagglutinin-neuraminidase (HN) glycoprotein and the fusion (F) glycoprotein. The F glycoprotein is pivotal, mediating membrane fusion between the virus and target cells, as well as facilitating syncytium formation, the merging of infected cells into larger, multi-nucleated entities.
Enhanced Syncytium Formation Leads to Increased Virus Growth
The study presents the isolation of a variant virus (Vr) from the wild-type C35 strain (WT) of hPIV1. This variant was found to induce pronounced syncytium formation in infected cells, leading to a larger focus area and accelerated virus growth compared to the WT. This outcome was attributed to a mutation resulting in an isoleucine-to-valine (I131V) substitution at position 131 in the F glycoprotein, with no concurrent changes observed in the HN glycoprotein.
The Magnitude of a Single Mutation
The significance of this amino acid substitution is underscored by the increased ability of the Vr to mediate cell-to-cell spread, essential for the virus’s infectious cycle. The Vr F glycoprotein not only enhances the formation of syncytia but also increases the focus area of cells infected by the WT strain when expressed. This discovery points to the possibility that hPIV1’s in vitro growth can be increased through mutations promoting direct cell-to-cell transmission by syncytium formation.
Implications for Virology and Antiviral Therapeutics
This finding has considerable implications for understanding the pathogenesis of hPIV1 and developing targeted antiviral strategies. By elucidating the fundamental processes that govern virus replication and spread, scientists and pharmaceutical researchers can devise more effective interventions against hPIV1.
Furthermore, this insight into the mutation-driven evolution of hPIV1’s infectivity provides a crucial perspective on how viral mutations can impact disease transmission and progression. It also emphasizes the need for continuous monitoring and research to stay ahead of potential variants with enhanced infectious capabilities.
The Study’s Methodology and Results
The research, led by Keijo Fukushima and his team, employed the hPIV1 plaque formation assay to isolate the variant virus. Following thorough sequence analysis of the spike glycoprotein genes, the team pinpointed the single amino acid change in the F glycoprotein. Subsequent experiments confirmed the enhanced functional effects attributed to this mutation.
This study not only contributes a notable advance to viral research but also underscores the incredible influence that even a single mutation can have on a virus’s behavior. As viruses continuously evolve, these discoveries are instrumental in providing us with the knowledge to anticipate and combat future outbreaks.
Moving Forward
In the continued fight against viral diseases, the research published in Biological & Pharmaceutical Bulletin paves the way for future studies. The team’s work at the University of Shizuoka demonstrates how a deeper understanding of viral protein functions can lead to better outbreak preparedness and response, highlighting the ever-present need for investment in scientific research.
References:
1. Fukushima, K., Takahashi, T., Takaguchi, M., Ito, S., Suzuki, C., Agarikuchi, T., Kurebayashi, Y., Minami, A., & Suzuki, T. (2019). A I131V Substitution in the Fusion Glycoprotein of Human Parainfluenza Virus Type 1 Enhances Syncytium Formation and Virus Growth. Biological & Pharmaceutical Bulletin, 42(5), 827–832. https://doi.org/10.1248/bpb.b18-00714
2. Collins, P. L., Chanock, R. M., & Murphy, B. R. (2001). Respiratory syncytial virus and parainfluenza virus. New England Journal of Medicine, 344(25), 1917-1928. https://doi.org/10.1056/NEJM200106213442507
3. Moscona, A. (2005). Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease. Journal of Clinical Investigation, 115(7), 1688-1698. https://doi.org/10.1172/JCI25669
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Keywords
1. Human Parainfluenza Virus Type 1
2. Viral Fusion Glycoprotein Mutation
3. Viral Syncytium Formation
4. Virus Cell-to-Cell Transmission
5. Parainfluenza Virus Infectivity Enhancement