PMID- 20883160 OWN - NLM STAT- MEDLINE DCOM- 20110113 LR - 20211020 IS - 1557-8976 (Electronic) IS - 0882-8245 (Print) IS - 0882-8245 (Linking) VI - 23 IP - 5 DP - 2010 Oct TI - Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs. PG - 457-66 LID - 10.1089/vim.2010.0051 [doi] AB - We performed a comprehensive analysis of innate and adaptive immune responses in dual-virus infected pigs to understand whether a pre-existing immunomodulatory respiratory viral infection affects the overall immunity to a subsequent porcine respiratory coronavirus (PRCV) infection in pigs. Pigs were either mock-infected or infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus known to cause immunosuppressive respiratory disease, and then pigs were co-infected with PRCV, which normally causes subclinical respiratory infection. We collected samples for six independent experiments from 178 pigs that were also used for pathological studies. We detected a significant reduction in innate NK-cell-mediated cytotoxic function in PRRSV-infected pigs, which was synergistically further decreased in pigs co-infected with PRCV. Subsequently, in association with clinical signs we observed elevated levels of proinflammatory (IL-6), Th-1 (IL-12), and regulatory (IL-10 and TGF-beta) cytokines. Increased frequencies of CD4CD8 double-positive T lymphocytes and myeloid cells, in addition to the elevated Th-1 and proinflammatory cytokines in dual-infected pigs, contributed to the severity of lung disease in pigs. The results of our study clarify how each virus modulates the host innate and adaptive immune responses, leading to inflammatory reactions and lung pathology. Thus measurements of cytokines and frequencies of immune cells may serve as indicators of the progression of respiratory viral co-infections, and provide more definitive approaches for treatment. FAU - Renukaradhya, Gourapura J AU - Renukaradhya GJ AD - Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691, USA. gourapura.1@osu.edu FAU - Alekseev, Konstantin AU - Alekseev K FAU - Jung, Kwonil AU - Jung K FAU - Fang, Ying AU - Fang Y FAU - Saif, Linda J AU - Saif LJ LA - eng GR - R01 AI060739/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Viral Immunol JT - Viral immunology JID - 8801552 RN - 0 (Cytokines) SB - IM MH - Animals MH - Coronavirus Infections/immunology/pathology/*veterinary/virology MH - Cytokines/immunology MH - *Immune Tolerance MH - Inflammation/pathology MH - Killer Cells, Natural/immunology MH - Lung/immunology/pathology/virology MH - Porcine Reproductive and Respiratory Syndrome/immunology/pathology/*virology MH - Porcine Respiratory Coronavirus/*immunology/pathogenicity MH - Porcine respiratory and reproductive syndrome virus/*immunology/pathogenicity MH - Swine MH - Swine Diseases/immunology/pathology/*virology MH - T-Lymphocyte Subsets/immunology PMC - PMC2967820 EDAT- 2010/10/05 06:00 MHDA- 2011/01/14 06:00 PMCR- 2011/10/01 CRDT- 2010/10/02 06:00 PHST- 2010/10/02 06:00 [entrez] PHST- 2010/10/05 06:00 [pubmed] PHST- 2011/01/14 06:00 [medline] PHST- 2011/10/01 00:00 [pmc-release] AID - 10.1089/vim.2010.0051 [pii] AID - 10.1089/vim.2010.0051 [doi] PST - ppublish SO - Viral Immunol. 2010 Oct;23(5):457-66. doi: 10.1089/vim.2010.0051.