Avian leukosis virus subgroup J (ALV-J) was first isolated from meat-type chickens in 1988. No field cases of ALV-J infection or tumors in layer chickens were observed worldwide until 2004. However, layer flocks in China have experienced outbreaks of this virus in recent years. The molecular epidemiology of ALV-J strains isolated from layer flocks was investigated. The env genes of 77.8% (21/27) of the ALV-J layer isolates with a high degree of genetic variation were significantly different from the env genes of the prototype strain of ALV-J (HPRS-103) and American and Chinese strains from meat-type chickens (designated ALV-J broiler isolates). A total of 205 nucleotides were deleted from the 3′ untranslated region of 89.5% (17/19) of the ALV-J layer isolates. Approximately 94.7% (16/17) of the layer isolates contained a complete E element of 146 to 149 residues. The U3 sequences of 84.2% (16/19) of the ALV-J layer isolates displayed less than 92.5% sequence homology to those of the ALV-J broiler isolates, although the transcriptional regulatory elements that are typical of avian retroviruses were highly conserved. Several unique nucleotide substitutions in the env gene, the U3 region, and the E element of most of the ALV-J layer isolates were detected. These results suggested that the env gene, E element, and U3 region in the ALV-J layer isolates have evolved rapidly and were significantly different from those of the ALV-J broiler isolates. These findings will contribute to a better understanding of the pathogenic mechanism of layer tumor diseases induced by ALV-J.

Infectious bursal disease (IBD) is an acute, highly contagious, immunosuppressive disease of chickens caused by the virus (IBDV), which critically threatens the development of the global chicken industry and causes huge economic losses. As a large country in the poultry industry, the epidemic history of IBDV in China for more than 40 years has been briefly discussed and summarized for the first time in this report. The first classic strain of IBDV appeared in China in the late 1970s. In the late 1980s and early 1990s, the very virulent IBDV (vvIBDV) rapidly swept across the entirety of China, threatening the healthy development of the poultry industry for more than 30 years. Variants of IBDV, after long-term latent circulation with the accumulation of mutations since the early 1990s, suddenly reappeared as novel variant strains (nVarIBDV) in China in the mid-2010s. Currently, there is a coexistence of various IBDV genotypes; the newly emerging nVarIBDV of A2dB1 and persistently circulating vvIBDV of A3B3 are the two predominant epidemic strains endangering the poultry industry. Continuous epidemiological testing and the development of new prevention and control agents are important and require more attention. This report is of great significance to scientific cognition and the comprehensive prevention and control of the IBDV epidemic.

The cellular DNA sensor cGMP-AMP synthase (cGAS) detects cytosolic viral DNA via the stimulator of interferon genes (STING) to initiate innate antiviral response. Herpesviruses are known to target key immune signaling pathways to persist in an immune-competent host. Marek’s disease virus (MDV), a highly pathogenic and oncogenic herpesvirus of chickens, can antagonize host innate immune responses to achieve persistent infection. With a functional screen, we identified five MDV proteins that blocked beta interferon (IFN-β) induction downstream of the cGAS-STING pathway. Specifically, the MDV major oncoprotein Meq impeded the recruitment of TANK-binding kinase 1 and IFN regulatory factor 7 (IRF7) to the STING complex, thereby inhibiting IRF7 activation and IFN-β induction. Meq overexpression markedly reduced antiviral responses stimulated by cytosolic DNA, whereas knockdown of Meq heightened MDV-triggered induction of IFN-β and downstream antiviral genes. Moreover, Meq-deficient MDV induced more IFN-β production than wild-type MDV. Meq-deficient MDV also triggered a more robust CD8+ T cell response than wild-type MDV. As such, the Meq-deficient MDV was highly attenuated in replication and lymphoma induction compared to wild-type MDV. Taken together, these results revealed that MDV evades the cGAS-STING DNA sensing pathway, which underpins the efficient replication and oncogenesis. These findings improve our understanding of the virus-host interaction in MDV-induced lymphoma and may contribute to the development of novel vaccines against MDV infection. Marek’s disease virus (MDV) is an avian oncogenic herpesvirus that causes a fatal disease in poultry worldwide. Chickens infected with MDV become more susceptible to secondary viral or bacterial infections. However, the mechanisms of MDV-induced immunosuppression and tumorigenesis remain largely unknown. The cGAS-STING pathway is crucial for innate immune responses against both microbial pathogens and intrinsic tumors. Here we identified the MDV oncoprotein, Meq, as an inhibitor of the cGAS-STING DNA-sensing pathway. Mechanistically, Meq interacted with STING and IRF7, and impaired the recruitment of TBK1 and IRF7 to the STING complex, thus inhibiting IRF7 activation and IFN-β induction. Loss of Meq potently enhanced innate immune response, while impaired the replication and oncogenesis of MDV in chickens. Our findings reveal an important mechanism of immune evasion of MDV, instructing us on the virus-host interaction in MDV-induced lymphoma and potential new means to develop MDV vaccine.

In the past 5 years, an atypical clinical outbreak of avian leukosis virus subgroup J (ALV-J), which contains a unique 205-nucleotide deletion in its 3′ untranslated region (3′UTR), has become epidemic in chickens in China. To determine the role of the 205-nucleotide deletion in the pathogenicity of ALV-J, a pair of viruses were constructed and rescued. The first virus was an ALV-J Chinese isolate (designated HLJ09SH01) containing the 205-nucleotide deletion in its 3′UTR. The second virus was a chimeric clone in which the 3′UTR contains a 205-nucleotide sequence corresponding to a region of the ALV-J prototype virus. The replication and pathogenicity of the rescued viruses (rHLJ09SH01 and rHLJ09SH01A205) were investigated. Compared to rHLJ09SH01A205, rHLJ09SH01 showed a moderate growth advantage in vitro and in vivo , in addition to exhibiting a higher oncogenicity rate and lethality rate in layers and broilers. Increased vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth receptor subtype 2 (VEGFR-2) expression was induced by rHLJ09SH01 more so than by rHLJ09SH01A205 during early embryonic vascular development, but this increased expression disappeared when the expression levels were normalized to the viral levels. This finding suggests that the expression of VEGF-A and VEGFR-2 is associated with viral replication and may also represent a novel molecular mechanism underlying the oncogenic potential of ALV-J. Overall, our findings not only indicate that the unique 205-nucleotide deletion in the ALV-J genome occurred naturally in China and contributes to increased pathogenicity but also point to the possible mechanism of ALV-J-induced oncogenicity.