Jam-a-independent, Antibody-mediated Uptake of Reovirus into Cells Leads to Apoptosis.
From: Department of Pediatrics, and Elizabeth B. Lamb Center for Pediatric Research, D7235 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Journal of virology
- Publish Date: Feb 2006
- ISSN: 0022-538X
- Volume: 80
- Issue: 3
- Pages: 1261-70
- Medium: Print
- Language: English
- Citation (JAMA): Danthi Pranav, Hansberger Mark W, Campbell Jacquelyn A, et al. Jam-a-independent, Antibody-mediated Uptake of Reovirus into Cells Leads to Apoptosis.. J. Virol. Feb 2006;80:1261-70
Abstract
Apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. Strain-specific differences in the capacity of reovirus to induce apoptosis segregate with the S1 and M2 gene segments, which encode attachment protein sigma1 and membrane penetration protein mu1, respectively. Virus strains that bind to both junctional adhesion molecule-A (JAM-A) and sialic acid are the most potent inducers of apoptosis. In addition to receptor binding, events in reovirus replication that occur during or after viral disassembly but prior to initiation of viral RNA synthesis also are required for reovirus-induced apoptosis. To determine whether reovirus infection initiated in the absence of JAM-A and sialic acid results in apoptosis, Chinese hamster ovary (CHO) cells engineered to express Fc receptors were infected with reovirus using antibodies directed against viral outer-capsid proteins. Fc-mediated infection of CHO cells induced apoptosis in a sigma1-independent manner. Apoptosis following this uptake mechanism requires acid-dependent proteolytic disassembly, since treatment of cells with the weak base ammonium chloride diminished the apoptotic response. Analysis of T1L x T3D reassortant viruses revealed that the mu1-encoding M2 gene segment is the only viral determinant of the apoptosis-inducing capacity of reovirus when infection is initiated via Fc receptors. Additionally, a temperature-sensitive, membrane penetration-defective M2 mutant, tsA279.64, is an inefficient inducer of apoptosis. These data suggest that signaling pathways activated by binding of sigma1 to JAM-A and sialic acid are dispensable for reovirus-mediated apoptosis and that the mu1 protein plays an essential role in stimulating proapoptotic signaling.
Mesh Headings (Keywords): Animals, Antibodies, Viral, Apoptosis, CHO Cells, Cell Adhesion Molecules, Cricetinae, Cytopathogenic Effect, Viral, Genes, Viral, Hela Cells, Humans, Mammalian orthoreovirus 3, Mice, Orthoreovirus, Mammalian, Receptors, Fc, Recombinant Proteins, Sequence Deletion, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 16415003
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