title: Quantification of the host response proteome after mammalian reovirus T1L infection.
abstract: All viruses are dependent upon host cells for replication. Infection can induce profound changes within cells, including apoptosis, morphological changes, and activation of signaling pathways. Many of these alterations have been analyzed by gene arrays to measure the cellular "transcriptome." We used SILAC (stable isotope labeling by amino acids in cell culture), combined with high-throughput 2-D HPLC/mass spectrometry, to determine relative quantitative differences in host proteins at 6 and 24 hours after infecting HEK293 cells with reovirus serotype 1 Lang (T1L). 3,076 host proteins were detected at 6 hpi, of which 132 and 68 proteins were significantly up or down regulated, respectively. 2,992 cellular proteins, of which 104 and 49 were up or down regulated, respectively, were identified at 24 hpi. IPA and DAVID analyses indicated proteins involved in cell death, cell growth factors, oxygen transport, cell structure organization and inflammatory defense response to virus were up-regulated, whereas proteins involved in apoptosis, isomerase activity, and metabolism were down-regulated. These proteins and pathways may be suitable targets for intervention to either attenuate virus infection or enhance oncolytic potential.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Berard
authors.forename: John P
authors.initials: JP
authors.lastname: Cortens
authors.forename: Oleg
authors.initials: O
authors.lastname: Krokhin
authors.forename: John A
authors.initials: JA
authors.lastname: Wilkins
authors.forename: Alberto
authors.initials: A
authors.lastname: Severini
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Coombs
mesh_terms: D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D057809:HEK293 Cells / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007553:Isotope Labeling; D030102:Orthoreovirus, Mammalian / Q000235:genetics / Q000472:pathogenicity; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D012088:Reoviridae Infections / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D011506:Proteins; D020543:Proteome