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Coinfection with Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) causes synergistic pathogenic effects and serious losses to the poultry industry. However, whether there is a synergism between the two viruses in viral replication and the roles of host factors in regulating MDV and REV coinfection remains elusive. In this study, we found that MDV and REV coinfection increased viral replication in coinfected cells as compared to a single infection in a limited period. Further, we explore the host cell responses to MDV and REV coinfection using tandem mass tag (TMT) peptide labeling coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS). Compared with MDV/REV-infected cells, 38 proteins increased (fold change &amp;gt; 1.2) and 60 decreased (fold change &amp;lt; 0.83) their abundance in MDV and REV coinfected cells. Differentially accumulated proteins (DAPs) were involved in important biological processes involved in the immune system process, cell adhesion and migration, cellular processes, and multicellular organismal systems. STRING analysis found that IRF7, MX1, TIMP3, and AKT1 may be associated with MDV and REV synergistic replication in chicken embryo fibroblasts (CEFs). Western blotting analysis showed that the selected DAPs were identical to the quantitative proteomics data. Taken together, we verified that MDV and REV can synergistically replicate in coinfected cells and revealed the host molecules involved in it. However, the synergistic pathogenesis of MDV and REV needs to be further studied.

Marek's Disease Virus and Reticuloendotheliosis Virus Coinfection Enhances Viral Replication and Alters Cellular Protein Profiles