Marek’s disease (MD) is a highly contagious lymphoproliferative and immunosuppressive disease of chickens and is responsible for significant economic losses to the poultry industry. The causative agent of MD is an oncogenic cell-associated alphaherpesvirus known as Marek’s disease virus (MDV). The International Committee on Taxonomy of Viruses classifies MDV-related viruses into three groups: gallid alphaherpesvirus 2 (GaHV-2, also known as MDV-1), GaHV-3 (previously referred to as MDV-2), and meleagrid herpesvirus type 1 (MeHV-1; turkey herpesvirus 1, HVT, previously MDV-3). GaHV-2 is pathogenic and induces tumours in susceptible chickens, whereas the other two species are non-pathogenic. According to its pathogenicity, GaHV-2 is further classified into four pathotypes: mild (m), virulent (v), very virulent (vv), and very virulent plus (vv+).
MD can be controlled by vaccination, with great efficacy against the development of the disease, resulting in reductions in economic losses to poultry farms since the 1970s[3, 4]. The live vaccines HVT (non-pathogenic MeHV-1), SB-1 (non-pathogenic GaHV-3), 814 (an effective attenuated GaHV-2 vaccine developed and used in China), and CVI988 (an effective attenuated GaHV-2 vaccine used commercially worldwide) as well as the bivalent vaccines HVT plus SB-1 and HVT plus CVI988 are some of the vaccines that have been used worldwide on poultry farms. Although these vaccines protect against tumours and mortality and provide lifelong immunity, vaccination does not induce sterile immunity, allowing for the replication and shedding of virulent challenge MDVs in chickens[6, 7]. Due to complicated interactions among the pathogens, vaccines, and hosts, the virulence of field MDV strains has increased, with viruses acquiring the ability to overcome the immune responses induced by the vaccines. The emergence of more virulent MDV variants may have devastating consequences for the poultry industry in the future. Thus, it is necessary to conduct surveillance studies to assess the prevalence of MDV on commercial poultry farms and develop more sustainable strategies against MDV in a timely manner.
In China, the vaccines HVT, CVI988, and 814 and the bivalent vaccine HVT plus SB-1 have been widely used on laying and breeding chicken farms for a few decades. However, MD outbreaks frequently occur in several provinces in China, even among chickens that have been inoculated with the commercial HVT plus CVI988 vaccines. Recently, a MDV strain isolated from a commercial layer farm vaccinated with HVT plus CVI988 in Colombia clusters with other vv + MDV strains by phylogenetic analysis and has similar characteristics as found in the proline rich region of Meq gene. Nevertheless, no field MDV strains have yet been reported from chicken farms vaccinated with HVT plus CVI988 in China.
Here, we isolated a highly virulent MDV strain (LZ1309) from a layer flock in the Gansu province of China that had received the HVT plus CVI988 vaccine. This represents the first instance of the isolation of a highly virulent MDV from chickens vaccinated with HVT plus CVI988 in China. Thus, the primary purpose of this study was to explore the pathogenic characteristics of the novel isolated MDV strain, the causes of MD vaccination failure, and the evolution of MDVs. Moreover, to gain a comprehensive understanding of the pathogenicity of the LZ1309 strain, our results indicate that a highly virulent MDV with the ability to override the immunoprotection of HVT plus CVI988, which is presently the most effective vaccine combination, is emerging in China. This study provides a basis for future investigations into more effective MDV prevention and treatment measures.