Reovirus-induced apoptosis of MDCK cells is not linked to viral yield and is blocked by Bcl-2.
In this study, we investigated the relationship between reovirus-induced apoptosis and viral growth. Madin-Darby canine kidney (MDCK) epithelial cells infected with prototype reovirus strains type 1 Lang (T1L) or type 3 Dearing (T3D) were found to undergo apoptosis, and T3D induced apoptosis of MDCK cells to a substantially greater extent than T1L. By using T1L x T3D reassortant viruses, we found that differences in the capacities of these strains to induce apoptosis are determined by the viral S1 and M2 gene segments. These genes encode viral outer-capsid proteins that play important roles in viral entry into cells. T1L grew significantly better in MDCK cells than T3D, and these differences in growth segregated with the viral L1 and M1 gene segments. The L1 and M1 genes encode viral core proteins involved in viral RNA synthesis. Bcl-2 overexpression in MDCK cells inhibited reovirus-induced apoptosis but did not substantially affect reovirus growth. These findings indicate that differences in the capacities of reovirus strains to induce apoptosis and grow in MDCK cells are determined by different viral genes and that premature cell death by apoptosis does not limit reovirus growth in MDCK cells.
Rodgers
S E
SE
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Barton
E S
ES
Oberhaus
S M
SM
Pike
B
B
Gibson
C A
CA
Tyler
K L
KL
Dermody
T S
TS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002213:Capsid / Q000235:genetics; D036022:Capsid Proteins; D002460:Cell Line; D004285:Dogs; D012089:Mammalian orthoreovirus 3 / Q000254:growth & development* / Q000502:physiology; D018165:Orthoreovirus / Q000254:growth & development* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
D036022:Capsid Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; C055356:mu1 protein, Reovirus; C031728:sigma 1 protein, reovirus; C091731:lambda3 protein, Reovirus; D012324:RNA-Dependent RNA Polymerase