Reovirus triggers cell type-specific proinflammatory responses dependent on the autocrine action of IFN-beta.
Resident cells of the respiratory and gastrointestinal tracts, including epithelial and fibroblast cells, are the initial sites of entry for many viral pathogens. We investigated the role that these cells play in the inflammatory process in response to infection with reovirus 1/L. In A549 human bronchial or HT-29 human colonic epithelial cells, interferon (IFN)-beta, regulated on activation T cell expressed and secreted (RANTES), IFN-gamma-inducible protein (IP)-10, and interleukin-8 were upregulated regardless of whether cells were infected with replication-competent or replication-deficient reovirus 1/L. However, in CCD-34Lu human lung fibroblast cells, IFN-beta, IP-10, and RANTES were expressed only after infection with replication-competent reovirus 1/L. Expression of interleukin-8 in CCD-34Lu fibroblast cells was viral replication independent. This differential expression of IFN-beta, RANTES, and IP-10 was shown to be due to the lack of induction of IFN regulatory factor-1 and -2 in CCD-34Lu fibroblast cells treated with replication-deficient reovirus 1/L. We have shown that cytokine and/or chemokine expression may not be dependent on viral replication. Therefore, treatment of viral infections with inhibitors of replication may not effectively alleviate inflammatory mediators because most viral infections result in the generation of replication-competent and replication-deficient virions in vivo.
Hamamdzic
D
D
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Phillips-Dorsett
T
T
Altman-Hamamdzic
S
S
London
S D
SD
London
L
L
D019898:Autocrine Communication / Q000276:immunology; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000821:virology; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression / Q000276:immunology; D019073:HT29 Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016899:Interferon-beta / Q000235:genetics* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D018165:Orthoreovirus; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012088:Reoviridae Infections / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology; D014779:Virus Replication / Q000276:immunology
D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016328:NF-kappa B; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D016899:Interferon-beta