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Biological studies of the fusion function of California serogroup Bunyaviruses
N Pobjecky1, J Smith, F Gonzalez-Scarano
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Abstract:
Like other enveloped viruses, La Crosse virus is capable of inducing membrane fusion after exposure to mild acid. This function is known to have biological significance at the level of the whole organism, since it has been related to infection in a mouse model. In this report the process of fusion-from-within (FFWI) for LAC and other members of the California serogroup of Bunyaviruses is characterized. Like fusion-from-without, FFWI is dependent on pH, temperature, and number of virus particles present in the supernatant of fusing cells. Electron micrographs demonstrate that LAC mediated cell membrane fusion is a rapid, multi-point event, and that other than fusion of their plasma membranes, the cells do not show any morphological change. In agreement with theory, lysosomotropic agents were capable of inhibiting La Crosse virus infection. This inhibition was not due to non-specific toxic effects on infected cells. Finally, fusion studies of other California serogroup members revealed minor differences in the pH of fusion induction in some strains. These differences were consistent with the known subtyping within the serogroup.
Insights
La Crosse virus induces cell fusion via a pH-dependent process, crucial for infection. This study characterizes fusion-from-within (FFWI) in Bunyaviruses, revealing insights into viral entry mechanisms.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Enveloped viruses, including La Crosse virus (LACV), utilize membrane fusion for cellular entry.
- This fusion process is critical for viral infection and pathogenesis, as demonstrated in mouse models.
- Fusion-from-within (FFWI) is a key mechanism by which enveloped viruses mediate cell-to-cell spread.
Purpose of the Study:
- To characterize the fusion-from-within (FFWI) process mediated by La Crosse virus (LACV).
- To investigate the influence of environmental factors (pH, temperature, viral load) on LACV-induced FFWI.
- To explore the potential of lysosomotropic agents as inhibitors of LACV infection and fusion.
Main Methods:
- Characterization of LACV-mediated FFWI under varying pH, temperature, and viral particle concentrations.
- Electron microscopy to visualize the morphological changes during LACV-induced cell-cell fusion.
- Assessment of lysosomotropic agent efficacy in inhibiting LACV infection and fusion.
Main Results:
- FFWI for LACV and other California serogroup Bunyaviruses is dependent on pH, temperature, and viral particle number.
- Electron microscopy revealed LACV-induced fusion as a rapid, multi-point event without significant cellular morphological alterations beyond plasma membrane fusion.
- Lysosomotropic agents effectively inhibited LACV infection without causing non-specific toxicity.
- Fusion studies identified minor variations in fusion pH induction among California serogroup strains, correlating with known subtyping.
Conclusions:
- La Crosse virus employs a fusion-from-within mechanism dependent on specific environmental conditions.
- Lysosomotropic agents represent a potential therapeutic strategy against LACV infection by inhibiting viral fusion.
- Variations in fusion pH among Bunyavirus strains provide insights into their classification and evolutionary relationships.