Responses of insect cells to baculovirus infection: protein synthesis shutdown and apoptosis.
Protein synthesis is globally shut down at late times postinfection in the baculovirus Autographa californica M nuclear polyhedrosis virus (AcMNPV)-infected gypsy moth cell line Ld652Y. A single gene, hrf-1, from another baculovirus, Lymantria dispar M nucleopolyhedrovirus, is able to preclude protein synthesis shutdown and ensure production of AcMNPV progeny in Ld652Y cells (S. M. Thiem, X. Du, M. E. Quentin, and M. M. Berner, J. Virol. 70:2221-2229, 1996; X. Du and S. M. Thiem, Virology 227:420-430, 1997). AcMNPV contains a potent antiapoptotic gene, p35, and protein synthesis arrest was reported in apoptotic insect cells induced by infection with AcMNPV lacking p35. In exploring the function of host range factor 1 (HRF-1) and the possible connection between protein synthesis shutdown and apoptosis, a series of recombinant AcMNPVs with different complements of p35 and hrf-1 were employed in apoptosis and protein synthesis assays. We found that the apoptotic suppressor AcMNPV P35 was translated prior to protein synthesis shutdown and functioned to prevent apoptosis. HRF-1 prevented protein synthesis shutdown even when the cells were undergoing apoptosis, but HRF-1 could not functionally substitute for P35. The DNA synthesis inhibitor aphidicolin could block both apoptosis and protein synthesis shutdown in Ld652Y cells infected with p35 mutant AcMNPVs but not the protein synthesis shutdown in wild-type AcMNPV-infected Ld652Y cells. These data suggest that protein synthesis shutdown and apoptosis are separate responses of Ld652Y cells to AcMNPV infection and that P35 is involved in inducing a protein synthesis shutdown response in the absence of late viral gene expression in Ld652Y cells. A model was developed for these responses of Ld652Y cells to AcMNPV infection.
Du
X
X
Department of Microbiology, Michigan State University, East Lansing 48824-1115, USA.
Thiem
S M
SM
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016367:Baculoviridae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004261:DNA Replication; D005814:Genes, Viral; D019476:Insect Proteins / Q000096:biosynthesis*; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D009036:Moths; D017924:Nucleopolyhedroviruses / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis
C099608:HRF-1 protein, Autographa californica nucleopolyhedrovirus; D019476:Insect Proteins; D014764:Viral Proteins; D016590:Aphidicolin; D008715:Methionine