Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

Zhou, Ping; Zhai, Shanli; Zhou, Xiang; Lin, Ping; Jiang, Tengfei; Hu, Xueying; Jiang, Yunbo; Wu, Bin; Zhang, Qingde; Xu, Xuewen; Li, Jin-ping; Liu, Bang

It has been shown in this study, that modulated inflammatory reaction, with a few proinflammatory cytokines upregulated (CCL2, CCL4L and its receptor CCR5, and CSF1) ( Table 4) , might contribute to the mild regional lung lesion observed at 5 and 7 dpi ( Figure 1C and D) . Besides, the complement system is one of the key players in the defense against infections. However, excessive activation of the complement can also exaggerate the disease induced by viral or bacterial infection. In 2009, a new H1N1 influenza A virus caused severe disease in naive middle-aged human individuals with preexisting immunity against seasonal strains, and this disease is reported to be induced through high titers of low-avidity nonprotective antibody and immune complex-mediated complement activation in the respiratory tract [44] . Excessive complement activation can contribute to organ damage in combination with the cytokine storm in the later stages of sepsis caused by bacterial infection [45] . It is reported that blocking complement activation can ameliorate hepatic inflammation mediated by the hepatitis C virus core protein [46] . Likewise, inhibition of complement with a potent C3 inhibitor (compstatin) in a baboon model of late-stage sepsis markedly improves organ preservation and other clinical parameters [47] . As it has been shown here, inhibition of the complement system might also be a contributor to the mild regional lung damage during HP-PRRSV infection. Interestingly, infection of HP-PRRSV in six-week-old crossbred weaned pigs (Landrace × Yorkshire) induces complement activation accompanied by severe lung damage [7] .