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Published on: September 5, 2016
Cellular processes essential for African swine fever virus to infect and replicate in primary macrophages
Sameh Basta1, Heidi Gerber, Alexander Schaub
1Department of Microbiology and Immunology, Queen's University, Kingston, ON, Canada. bastas@queensu.ca
Abstract:
The macrophage (Mø) is an essential immune cell for innate immunity. Such cells are targeted by African swine fever virus (ASFV). The early phases of infection with ASFV have been previously characterized in non-leukocyte cells such as Vero cells. Here, we report on several additional key parameters that ASFV utilizes during the infection of primary Mø. Related to virus infection, we established that receptor-mediated endocytosis of the virus by Mø is not the exclusive means of entry to infect the host cells. Analysis of the ensuing processes identified divalent cation-dependent activities to be particularly important, relating to the virus requirement for microtubule assembly needed for endocytic and endosomal processing. Actin-dependent endocytosis and endocytic flux involving microtubule activity are also implicated, pointing to entry via phagocytosis. Subsequently, the virus avoids terminal degradation by circumventing mature lysosome activities, including autophagosome-lysosome delivery. Nevertheless, the replicative cycle is apparently dependent on certain lysosomal functions, i.e. activities sensitive to propylamine are essential for the virus, whereas vinblastine- and leupeptin-sensitive functions only partially influence viral replication. The present work has identified cellular processes essential for ASFV to infect and replicate in the macrophage. These findings will improve our understanding of the cellular pathways employed by viruses infecting immune scavenger cells.
Insights
African swine fever virus (ASFV) infects macrophages through multiple entry routes, not just receptor-mediated endocytosis. The virus utilizes specific cellular processes for replication, avoiding lysosomal degradation while depending on certain lysosomal functions.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Macrophages (Mø) are crucial innate immune cells targeted by African swine fever virus (ASFV).
- Previous ASFV infection studies focused on non-leukocyte cells like Vero cells.
- Understanding ASFV's interaction with primary macrophages is essential for controlling swine fever.
Purpose of the Study:
- To characterize key parameters of ASFV infection in primary macrophages.
- To elucidate the entry mechanisms and intracellular processing of ASFV in Mø.
- To identify cellular processes vital for ASFV replication within macrophages.
Main Methods:
- Investigated ASFV entry into primary macrophages, assessing receptor-mediated endocytosis and alternative pathways.
- Analyzed the roles of divalent cations, microtubule assembly, and actin-dependent processes in viral entry and trafficking.
- Examined ASFV's interaction with lysosomes and autophagosomes, evaluating the impact of specific inhibitors on viral replication.
Main Results:
- ASFV entry into macrophages is not solely receptor-mediated endocytosis; phagocytosis is also implicated.
- Divalent cations and microtubule assembly are critical for ASFV endocytic and endosomal processing.
- ASFV circumvents mature lysosome degradation but requires specific propylamine-sensitive lysosomal functions for replication.
Conclusions:
- ASFV employs diverse cellular mechanisms for entry and replication in macrophages.
- The virus strategically manipulates host cell machinery, including endocytic pathways and lysosomal functions.
- These findings enhance understanding of viral pathogenesis in immune scavenger cells, aiding in disease control strategies.
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