Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCVs) are two major viruses that affect pigs. Coinfections between PRRSV and PCV2 are frequently reported in most outbreaks, with clinical presentations involving dyspnea, fever, reduced feed intake, weight loss, and death in fattening pigs. The NADC30-like PRRSV and PCV2d are the main circulating virus strains found in China. This study determines the impact of NADC30-like PRRSV and PCV2d mono-infection and coinfection on the immune system, organ pathology, and viral shedding in five-week-old post-weaned pigs. Pigs were randomly divided into six groups: PBS, PRRSV, PCV2, PRRSV-PCV2 coinfection (co), and PRRSV-PCV2 or PCV2-PRRSV sequential infections. Fever, dyspnea, decreased feed intake, weight loss, and pig deaths occurred in groups infected with PRRSV, Co-PRRSV-PCV2, and PRRSV-PCV2. The viral load was higher in Co-PRRSV-PCV2, PRRSV-PCV2, and PCV2-PRRSV than those mono-infected with PRRSV or PCV2. Additionally, cytokines (IFN-γ, TNF-α, IL-4, and IL-10) produced by pigs under Co-PRRSV-PCV2 and PRRSV-PCV2 groups were more intense than the other groups. Necropsy findings showed hemorrhage, emphysema, and pulmonary adhesions in the lungs of pigs infected with PRRSV. Smaller alveoli and widened lung interstitium were found in the Co-PRRSV-PCV2 and PRRSV-PCV2 groups. In conclusion, PRRSV and PCV2 coinfection and sequential infection significantly increased viral pathogenicity and cytokine responses, resulting in severe clinical signs, lung pathology, and death.
As a member of the Alphavirus, Getah virus (GETV) was becoming more serious and posing a serious threat to animal safety and public health. However, the circulation, distribution and evolution of GETV is not well understood. Hence, we integrated a variety of bioinformatic methodologies, from genomic alterations to systematic analysis, phylogeography, selection, adaptive analysis, prediction of protein modification, structural biology and molecular dynamics simulations to understand the characteristics of GETV. The results of phylogeography and molecular evolution show that due to the lack of vaccine, GETV is rapidly expanding its host range and geographical distribution at a high evolutionary rate. We also predicted the important modification sites, and identified the adaptive and active selection sites. Finally, the analysis of spatial structure and function showed that six adaptive sites may be related to the structural stability, receptor binding ability, immunogenicity and immune evasion of the virus, respectively. The data from this study have important implications for the understanding of ongoing GETV outbreaks worldwide and will guide future efforts to develop effective preventive and control measures against GETV. In particular, biosafety measures should be strengthened immediately to prevent GETV from becoming a pandemic, especially in China, South Korea and Japan.
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