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Innate immune genes play an important role in the immune responses to Rous sarcoma virus (RSV)-induced tumor formation and metastasis. Here, we determined in vivo expression of chemokines, innate immune and apoptotic genes in Synthetic Broiler Dam Line (SDL) chickens following RSV-A infection. The mRNA expression of genes was determined at the primary site of infection and in different organs of progressor, regressor and non-responder chicks, using RT-qPCR. Our results indicated a significant upregulation of: (1) chemokines, such as MIP1β and RANTES, (2) the innate immune gene TLR4, and (3) p53, a tumor-suppressor gene, at the site of primary infection in progressor chickens. In contrast, inducible nitric oxide synthase (iNOS) gene expression was significantly downregulated in progressor chicks compared to uninfected, control chicks. All of the innate immune genes were significantly upregulated in the lungs and liver of the progressor and regressor chicks compared to control chicks. In the spleen of progressor chicks, RANTES, iNOS and p53 gene expression were significantly increased, whereas MIP1β and TLR4 gene expression was significantly downregulated, compared to control chicks. The lungs and livers of non-responder chicks expressed a low level of iNOS and MIP1β, whereas RANTES, TLR4, and p53 gene expression were significantly upregulated compared to uninfected control chicks. In addition, there was a significant downregulation of RANTES, MIP1β, and TLR4 gene expression in non-responder chicks. These results suggest the different response to infection of chicks with RSV-A is due to differential changes in the expression of innate immune genes in different organs., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)