Avian leukosis virus subgroup J and reticuloendotheliosis virus coinfection induced TRIM62 regulation of the actin cytoskeleton

Abstract

Background: Coinfection with avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) is common in chickens, and the molecular mechanism of the synergistic pathogenic effects of the coinfection is not clear. Exosomes have been identified as new players in the pathogenesis of retroviruses. The different functions of exosomes depend on their cargo components. Objectives: The aim of this study was to investigate the function of co-regulation differentially expressed proteins in exosomes on coinfection of ALV-J and REV. Methods: Here, viral replication in CEF cells infected with ALV-J, REV or both was detected by immunofluorescence microscopy. Then, we analyzed the exosomes isolated from supernatants of chicken embryo fibroblast (CEF) cells single infected and coinfected with ALV-J and REV by mass spectrometry. KEGG pathway enrichment analyzed the co-regulation differentially expressed proteins in exosomes. Next, we silenced and overexpressed tripartite motif containing 62 (TRIM62) to evaluate the effects of TRIM62 on viral replication and the expression levels of NCK-association proteins 1 (NCKAP1) and actin-related 2/3 complex subunit 5 (ARPC5) determined by quantitative reverse transcription polymerase chain reaction. Results: The results showed that coinfection of ALV-J and REV promoted the replication of each other. Thirty proteins, including TRIM62, NCK-association proteins 1 (NCKAP1, also known as Nap125), and Arp2/3-5, ARPC5, were identified. NCKAP1 and ARPC5 were involved in the actin cytoskeleton pathway. TRIM62 negatively regulated viral replication and that the inhibition of REV was more significant than that on ALV-J in CEF cells coinfected with TRIM62. In addition, TRIM62 decreased the expression of NCKAP1 and increased the expression of ARPC5 in coinfected CEF cells. Conclusions: Collectively, our results indicated that coinfection with ALV-J and REV competitively promoted each other's replication, the actin cytoskeleton played an important role in the coinfection mechanism, and TRIM62 regulated the actin cytoskeleton.

Current Epidemiology and Co-Infections of Avian Immunosuppressive and Neoplastic Diseases in Chicken Flocks in Central China

“…In recent years, outbreaks of avian immunosuppressive and neoplastic diseases such as MD, AL, and RE have been frequently reported in chicken flocks worldwide, including in China [2,[9][10][11][13][14][15][20][21][22][23][27][28][29][30]. Especially during 2020-2022, a concentrated outbreak of suspected neoplastic diseases occurred in poultry farms from the South to North of China, but the main reasons remained unclear.…”

“…Usually, monoinfection of REV does not present apparent clinical symptoms and is mostly ignored. Once co-infected with other pathogens, especially with MDV and ALV-J, it shows obvious clinical symptoms and immunosuppressions, increases the incidence of tumours in infected chickens, and reduces the efficacy of other vaccines, which finally leads to more serious economic losses [20,21]. Currently, no effective vaccine is available for the prevention and control of REV either.…”

Viral Coinfections

“…Further studies have shown that host proteins such as IRF7, MX1, TIMP3, and AKT1 may be related to the synergy of MDV and REV. In the coinfection of the Avian leukosis virus subgroup J (ALV-J) and REV, host protein TRIM62 increases replication of the two viruses by regulating the actin cytoskeleton [113].…”

Characterization of the Role of Extracellular Vesicles Released from Chicken Tracheal Cells in the Antiviral Responses against Avian Influenza Virus

“…The contents and specific regulatory roles of EVs are poorly described in the context of infectious diseases in chickens. The few studies that have characterized the contents of EVs in the context of immune responses in chickens focus primarily on miRNA profiles, with little focus on protein content; therefore, studies are required to evaluate the role of EV protein content in the induction and modulation in the host response to viral infections [19][20][21][22][23][24][25][26]. For example, a recent study evaluated the proteomic profile of serum exosomes from Marek's Disease Virus (MDV)-vaccinated and protected and lymphoma-bearing chickens and identified potential biomarkers for the disease [24].…”