Abstract

   Subgroup J avian leukosis virus (ALV-J) is an oncogenic retrovirus that
   causes immunosuppression and enhances susceptibility to secondary
   infection. The innate immune system is the first line of defense in
   preventing bacterial and viral infections, and dendritic cells (DCs)
   play important roles in innate immunity. Because bone marrow is an
   organ that is susceptible to ALV-J, the virus may influence the
   generation of bone marrow-derived DCs. In this study, DCs cultured in
   vitro were used to investigate the effects of ALV infection. The
   results revealed that ALV-J could infect these cells during the early
   stages of differentiation, and infection of DCs with ALV-J resulted in
   apoptosis. miRNA sequencing data of uninfected and infected DCs
   revealed 122 differentially expressed miRNAs, with 115 demonstrating
   upregulation after ALV-J infection and the other 7 showing significant
   downregulation. The miRNAs that exhibited the highest levels of
   upregulation may suppress nutrient processing and metabolic function.
   These results indicated that ALV-J infection of chicken DCs could
   induce apoptosis via aberrant microRNA expression. These results
   provide a solid foundation for the further study of epigenetic
   influences on ALV-J-induced immunosuppression.
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   Avian leukosis viruses (ALVs) are a group of avian retroviruses that
   induce tumors in chickens[32]^1. Chicken ALVs are classified into six
   subgroups (A-E and J) on the basis of the envelope glycoprotein
   responsible for viral interference patterns, virus neutralization, and
   host range[33]^2,[34]^3. In recent decades, ALV-J has become epidemic,
   emerging in commercial layers and local breed flocks throughout
   China[35]^4. ALV-J, which mainly induces myeloid leukosis, causes more
   serious damage than other virus subgroups[36]^5. Many recent studies
   have found that ALV-J and other subgroups are important coinfection
   factors in avian diseases[37]^6,[38]^7,[39]^8. ALV infection with a
   concomitant enhanced secondary infection is likely the outcome of
   immunosuppression; however, the mechanism of this immunosuppression has
   not been clarified[40]^9.

   Dendritic cells (DCs), which were identified in mouse spleen tissue by
   Steinman and Cohn in 1973 and named for their typical
   morphology[41]^10,[42]^11, are professional antigen-presenting cells of
   the immune system that have the unique capacity to initiate primary
   immune responses[43]^12,[44]^13,[45]^14. DCs can regulate the immune
   response, and these cells express many different pathogen recognition
   receptors, such as Toll-like receptors, which are helpful for antigen
   presentation[46]^15. These functions are dependent on DC maturation,
   which is regulated largely by microRNAs
   (miRNAs)[47]^16,[48]^17,[49]^18,[50]^19.

   As a retrovirus, the ALV provirus can randomly integrate into the host
   genome, which may result in the deregulation of gene expression,
   especially the expression of various regulatory factors such as
   miRNAs[51]^20. The mechanism of ALV provirus integration is unclear;
   thus, ALV integration is often deemed random. However, some references