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Published on: October 21, 2012
The African swine fever virus dynein-binding protein p54 induces infected cell apoptosis
Bruno Hernáez1, Gema Díaz-Gil, Mónica García-Gallo
1Dpto. Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ctra. de la Coruña Km 7, 28040 Madrid, Spain.
Abstract:
A specific interaction of ASFV p54 protein with 8 kDa light chain cytoplasmic dynein (DLC8) has been previously characterized and this interaction is critical during virus internalization and transport to factory sites. During early phases of infection, the virus induces the initiation of apoptosis triggering activation of caspase-9 and -3. To analyze the role of the structural protein p54 in apoptosis, transient expression experiments of p54 in Vero cells were carried out which resulted in effector caspase-3 activation and apoptosis. Interestingly, p54 mutants, lacking the 13 aa dynein-binding motif lose caspase activation ability and pro-death function of p54. This is the first reported ASFV protein which induces apoptosis.
Insights
African Swine Fever Virus (ASFV) protein p54 induces apoptosis by interacting with dynein light chain 8 (DLC8). Mutants lacking this interaction lose their ability to activate caspases and induce cell death.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- African Swine Fever Virus (ASFV) protein p54 interacts with dynein light chain 8 (DLC8), crucial for viral entry and intracellular transport.
- ASFV infection initiates apoptosis, involving caspase-9 and caspase-3 activation during early infection stages.
Purpose of the Study:
- To investigate the role of ASFV p54 protein in inducing apoptosis.
- To determine if the interaction between p54 and DLC8 is essential for p54-mediated apoptosis.
Main Methods:
- Transient expression of ASFV p54 in Vero cells.
- Analysis of effector caspase-3 activation and apoptosis induction.
- Creation and testing of p54 mutants lacking the DLC8-binding motif.
Main Results:
- Transient expression of ASFV p54 induced caspase-3 activation and apoptosis in Vero cells.
- ASFV p54 mutants lacking the dynein-binding motif failed to activate caspases.
- These mutants also lost their pro-death function, indicating the DLC8 interaction is critical.
Conclusions:
- ASFV p54 is the first reported ASFV protein with the ability to induce apoptosis.
- The interaction of p54 with DLC8 is essential for its apoptotic function and caspase activation.
- This finding provides new insights into ASFV pathogenesis and host-cell manipulation.
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