Huijuan Xu

Viral co-infections pose significant challenges, causing substantial economic losses worldwide in the poultry industry. Among these, avian lLeukosis virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) are particularly concerning, as they frequently lead to co-infections in chickens, further compromising their immune defenses, increasing susceptibility to secondary infections and diminishing vaccine efficacy. While our previous studies have examined the pathogenicity and immunosuppressive effects of these co-infections in vitro and in vivo, the key genes and molecular pathways involved remain largely unexplored. This study investigates the synergistic effects of co-infection with ALV-J and CIAV through comprehensive transcriptome analysis using high-throughput sequencing. We identified 1007 differentially expressed mRNAs (DEmRNAs) and 62 differentially expressed miRNAs (DEmiRNAs) associated with the synergistic activation effects of co-infection, along with 331 DEmRNAs and 62 DEmiRNAs linked to specific activation processes. Notably, the immune suppression observed in co-infected chickens may be influenced by the enhanced utilization of reactive oxygen species (ROS) and oxidative stress pathways, which impact host immune responses. Furthermore, co-infection appears to employ distinct immune evasion strategies through the modulation of rRNA metabolism, differing from single infections. These insights provide a deeper understanding of the molecular mechanisms underlying immune suppression during viral co-infections and help develop targeted therapies and improve disease control in poultry, reducing economic losses.

In the realm of poultry production, viral superinfections pose significant challenges, causing substantial economic losses worldwide. Among these, avian leukosis virus subgroup J (ALV-J) and infectious bursal disease virus (IBDV) are particularly concerning as they frequently lead to superinfections in chicken, further exacerbating production losses and health complications. Our previous research delved into the pathogenicity and immunosuppressive effects of these superinfections through in vitro and in vivo analyses. Yet, the underlying key genes and pathways governing this phenomenon remained elusive. In this study, we randomly selected three chickens at 21 days post infection from each treatment group (ALV-J, IBDV, ALV-J+IBDV, and control group) to collect the bursa of Fabricius samples for full transcriptome analysis. Utilizing these data, we constructed a comprehensive circRNA/lncRNA-miRNA-mRNA network which elucidated both synergistic and specific activations during the superinfection. Notably, three pivotal genes (FILIP1L, DCX, and MYPN) were pinpointed in datasets reflecting synergistic activations. Conversely, four other genes (STAP, HKR6, XKR4, and TLR5) emerged in datasets associated with specific activations. Further exploration revealed diverse significant GO terms and pathways associated with both synergistic and distinct activation processes. These ceRNA network and core genes potentially wield substantial influence over the synergistic or specific activation of tumorigenesis and pathogenesis induced by ALV-J and IBDV. These findings could help develop targeted therapies and improve disease control in poultry, reducing economic losses.

Subgroup J avian leukemia virus (ALV-J) and chicken infectious anemia virus (CIAV) are widely acknowledged as significant immunosuppressive pathogens that commonly co-infect chickens, causing substantial economic losses in the poultry industry. However, whether co-infection of ALV-J and CIAV have synergistic pathogenicity remains uncertain. To explore their synergistic pathogenesis, we established a co-infection model of ALV-J and CIAV in HD11 cells and specific-pathogen-free (SPF) chickens. We discovered that ALV-J and CIAV can synergistically promote the secretion of IL-6, IL-10, IFN-α, and IFN-γ and apoptosis in HD11 cells. In vivo, compared to the ALV-J and CIAV mono-infected group, the mortality increased significantly by 27% (20 to 47%) and 14% (33 to 47%) in the co-infected group, respectively. We also discovered that ALV-J and CIAV synergistically inhibited weight gain and exhibited more severe organ damage in co-infected chickens. Furthermore, we found that CIAV can promote the replication of ALV-J in HD11 cells and significantly enhance ALV-J viral load in blood and tissues of co-infected chickens, but ALV-J cannot promote the replication of CIAV. Moreover, by measuring the immune organ indexes and proportions of blood CD3⁺CD4⁺ and CD3⁺CD8⁺ lymphocytes, more serious instances of immunosuppression were observed in ALV-J and CIAV co-infected chickens than in mono-infected chickens. Taken together, our findings demonstrate that ALV-J and CIAV synergistically enhance pathogenicity and immunosuppression.