*2.10. Clinical Performance and Gross Lesions of Lung*

The clinical performance of all of the piglets after the HP-PRRSV JXA1 challenge were observed and scored daily, as described previously [26]. Briefly, the scores, ranged from 0 to 5, represent the severity of clinical symptoms, which including behavior, appetite and respiration. The total score for clinical performance was calculated by the sum of the evaluation index daily. The lung injury of each group was evaluated by necropsy at 7 dpi and 15 dpi. Macroscopic gross lesions of each lobe were determined as the percentage of lung with visible pneumonia and scored, while the obtained lung tissue of each group were used to perform histological pathology analysis as described [27].

#### *2.11. Ethics Statement*

Animal experiments in this study were approved by Laboratory Animal Committee of South China Agricultural University (No. 2019C001). All piglets were raised in the animal facility of SCAU, and all operations were in accordance with the animal ethics guidelines and approved protocols.

#### *2.12. Statistical Analysis*

All data of each assay represents at least two separate experiments and were determined in triplicate. The results collected from triplicate determinations were analyzed as the means ± standard deviations (SD). Data difference of each experiment was analyzed by one-way Analysis of Variance (ANOVA) followed by the Tukey's t-test in GraphPad Prism 7.0 software (San Diego, CA). \* *p* < 0.05, \*\* *p* < 0.01, \*\*\* *p* < 0.001 and \*\*\*\* *p* < 0.0001 were considered to be statistically significant at different levels.

#### **3. Results**
