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This Article Full Text (Papers in Press[PDF]) All Versions of this Article: vir.0.014001-0v1 90/11/2713    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jung, K. Articles by Saif, L. J Search for Related Content PubMed PubMed Citation Articles by Jung, K. Articles by Saif, L. J Agricola Articles by Jung, K. Articles by Saif, L. J

Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

¹ Ohio State University;
² South Dakota State University

³ E-mail: saif.2{at}osu.edu

The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). Our study demonstrates that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. We established an innate immunosuppressive respiratory virus infection by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV), and then 10 days later, we exposed the pigs to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, higher incidence of fever and more severe pneumonia compared to either single infection. Significant suppression of innate immune responses [reduced interferon (IFN)-alpha levels in lung and blood natural killer (NK) cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in lung and a trend toward increased serum Th1 (IFN-gamma) but decreased Th2 (IL-4) responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by in situ TUNEL assay, suggesting increased PRRSV replication in PAMs. Collectively, our observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-alpha) and later adaptive Th1 (IFN-gamma) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. Our study provides new insights into host-pathogen interactions related to co-infections by CoVs and other respiratory viruses.

Received 5 June 2009; accepted 30 July 2009.