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
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
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DOI：
10.1099/vir.0.014001-0
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发表时间：
2009-11-01
影响因子：
3.8
通讯作者：
Saif, Linda J.
中科院分区：
文献类型：
--
作者：
Jung, Kwonil;Renukaradhya, Gourapura J.;Saif, Linda J.
先天免疫应答对于宿主防御呼吸道冠状病毒（CoV）至关重要。这项研究表明，正在进行的呼吸道病毒感染损害先天免疫反应，并影响呼吸道CoV合并感染的发病机制。用猪繁殖与呼吸综合征病毒（PRRSV）感染断奶仔猪，建立先天性免疫抑制性呼吸道病毒感染模型，10 d后，将仔猪暴露于猪呼吸道冠状病毒（PRCV）中。与任何一种单一感染相比，PRRSV/PRCV双重感染的猪体重增加减少，发烧和严重肺炎的发病率更高。在双重感染的猪中观察到持续的PRRSV感染对先天免疫应答的显著抑制[肺中α干扰素（IFN-α）水平降低和血液自然杀伤细胞细胞毒性降低]，这与PRCV感染早期期间的肺炎加重一致。随后的PRCV感染导致肺中PRRSV复制增强，血清辅助性T细胞1型（Th 1）（IFN-γ）应答增加，但Th 2 [白细胞介素（IL）-4]应答减少，进一步加重了PRRSV肺炎。PRCV感染后，发生了更严重的PRRSV相关肺泡巨噬细胞（PAM）凋亡，通过原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法测定，表明增加了PRRSV在PAM中的复制。总的来说，这些观察结果表明，通过早期先天性（IFN-α）和后来的适应性Th 1（IFN-γ）和Th 2（IL-4）免疫应答，PRCV和PRRSV之间的相互作用。这些发现表明，现有的免疫调节呼吸道病毒合并感染可能是呼吸道CoV疾病中更严重肺炎的一个促成因素。这项研究为与CoV和其他呼吸道病毒合并感染相关的宿主-病原体相互作用提供了新的见解。
The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-alpha) levels in the lungs and reduced blood natural killer 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 the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-gamma) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these 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. This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses.