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Interaction of African swine fever virus with macrophages
A Alcamí1, A L Carrascosa, E Viñuela
1Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma, Madrid, Spain.
Abstract:
Morphological data obtained by electron microscopy have shown that African swine fever virus adapted to VERO cells enters swine macrophages, its natural host cell, by a mechanism of receptor-mediated endocytosis. Binding studies with 3H-labeled virus and competition experiments with UV-inactivated virus have shown that the virus entry that leads to a productive infection in swine macrophages is mediated by saturable binding sites on the plasma membrane. The virus also penetrated into rabbit macrophages that do not produce infectious virus and initiated the synthesis of some early viral proteins; however, the viral replication cycle was aborted since viral DNA synthesis did not occur. The interaction of ASF virus particles with rabbit macrophages was mediated by nonsaturable binding sites, suggesting that the lack of specific receptors in these cells may be related to the absence of a productive infection. A similar abortive infection was detected in macrophages from other virus-resistant animal species.
Insights
African swine fever virus enters swine macrophages via receptor-mediated endocytosis, requiring saturable binding sites for productive infection. Resistance in other species may stem from a lack of these specific viral receptors.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- African swine fever virus (ASFV) is a significant pathogen affecting swine populations globally.
- Understanding the cellular mechanisms of ASFV entry is crucial for developing effective control strategies.
- Macrophages are the natural host cells for ASFV, but the precise entry pathways and host cell interactions are not fully elucidated.
Purpose of the Study:
- To investigate the mechanism of African swine fever virus entry into swine macrophages.
- To identify the role of specific binding sites in productive ASFV infection.
- To compare ASFV interaction with macrophages from susceptible and resistant animal species.
Main Methods:
- Electron microscopy was used to observe viral entry into swine macrophages.
- Binding studies with radiolabeled ASFV and competition assays with UV-inactivated virus were performed.
- Viral protein synthesis and DNA replication were assessed in infected macrophages from different species.
Main Results:
- ASFV enters swine macrophages through receptor-mediated endocytosis, involving saturable binding sites on the cell membrane.
- In rabbit macrophages, ASFV entry occurred but resulted in an abortive infection, with limited viral protein synthesis and no DNA replication.
- Non-saturable binding interactions were observed in rabbit macrophages, suggesting a lack of specific receptors contributes to resistance.
Conclusions:
- Receptor-mediated endocytosis and specific, saturable binding sites are essential for productive African swine fever virus infection in swine macrophages.
- The absence of specific viral receptors in macrophages of resistant species, like rabbits, likely explains the abortive nature of the infection.
- These findings provide insights into ASFV host specificity and potential targets for antiviral interventions.