Endogenous avian leukosis virus in combination with serotype 2 Marek's disease virus significantly boosted the incidence of lymphoid leukosis-like bursal lymphomas in susceptible chickens

Authors: Mays, Jody; BLACK-PYRKOSZ, ALEXIS - Michigan State University; MANSOUR, TAMER - Michigan State University; SCHUTTE, BRIAN - Michigan State University; CHANG, SHUANG - US Department Of Agriculture (USDA); DONG, KUNZHE - Orise Fellow; HUNT, HENRY - US Department Of Agriculture (USDA); FADLY, ALY - US Department Of Agriculture (USDA); ZHANG, LEI - Chinese Academy Of Agricultural Sciences; Zhang, Huanmin

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/10/2019
Publication Date: 11/13/2019
Publication URL: https://handle.nal.usda.gov/10113/6759787
Citation: Mays, J.K., Black-Pyrkosz, A., Mansour, T., Schutte, B.C., Chang, S., Dong, K., Hunt, H.D., Fadly, A.M., Zhang, L., Zhang, H. 2019. Endogenous avian leukosis virus in combination with serotype 2 Marek’s disease virus boosted the incidence of LL-like bursal lymphomas in susceptible chickens. Journal of Virology. 93:e00861-19. https://doi.org/10.1128/JVI.00861-19.
DOI: https://doi.org/10.1128/JVI.00861-19

Interpretive Summary: Sporadic avian leukosis virus (ALV)-like bursal lymphomas, also known as spontaneous lymphoid leukosis (LL)-like tumors, are a cancerous disease of chickens observed in some experimental and commercial lines of chickens where no known etiologic agents were detected. Recently the LL-like lymphomas were observed in some commercial broiler flocks and two new non-pathogenic strains of avian retroviruses were isolated from the farms. We have molecularly characterized the two individual field strains of non-pathogenic avian viruses and tested the viruses in an experimental line of chickens under controlled conditions. Our data showed that either of the two strains of viruses failed to cause additional LL-like lymphoma cases but in combination with a non-pathogenic Marek’s disease virus, known as SB-1, both did boost the disease incidence significantly. Genomic analyses of LL-like lymphoma tissues again normal bursal tissues suggested that the LL-like lymphoma formation may involve many chicken genes and multiple genetic networks. These findings may lead to the advanced understanding on this chicken disease and facilitate control strategy development in the near future.

Technical Abstract: In 2010, sporadic cases of avian leukosis virus (ALV)-like bursal lymphoma, also known as spontaneous lymphoid leukosis (LL)-like tumors, were identified in two commercial broiler breeder flocks in the absence of exogenous ALV infection. Two individual ALV subgroup E (ALV-E) field strains, designated AF227 and AF229, were isolated from two different breeder farms. The role of these ALV-E field isolates in development of and the potential joint impact in conjunction with a Marek’s disease virus (MDV) vaccine (SB-1) were further characterized in chickens of an experimental line and commercial broiler breeders. The experimental line 0.TVB*S1, commonly known as the rapid feathering-susceptible (RFS) line, of chickens lacks all endogenous ALV and is fully susceptible to all subgroups of ALV, including ALV-E. Spontaneous LL-like tumors occurred following infection with AF227, AF229, and a reference ALV-E strain, RAV60, in RFS chickens. Vaccination with serotype 2 MDV, SB-1, in addition to AF227 or AF229 inoculation, significantly enhanced the spontaneous LL-like tumor incidence in the RFS chickens. The spontaneous LL-like tumor incidence jumped from 14% by AF227 alone to 42 to 43% by AF227 in combination with SB-1 in the RFS chickens under controlled conditions. RNA-sequencing analysis of the LL-like lymphomas and nonmalignant bursa tissues of the RFS line of birds identified hundreds of differentially expressed genes that are reportedly involved in key biological processes and pathways, including signaling and signal transduction pathways. The data from this study suggested that both ALV-E and MDV-2 play an important role in enhancement of the spontaneous LL-like tumors in susceptible chickens. The underlying mechanism may be complex and involved in many chicken genes and pathways, including signal transduction pathways and immune system processes, in addition to reported viral genes. IMPORTANCE Lymphoid leukosis (LL)-like lymphoma is a low-incidence yet costly and poorly understood disease of domestic chickens. The observed unique characteristics of LL-like lymphomas are that the incidence of the disease is chicken line dependent; pathologically, it appeared to mimic avian leukosis but is free of exogenous ALV infection; inoculation of the nonpathogenic ALV-E or MDV-2 (SB-1) boosts the incidence of the disease; and inoculation of both the nonpathogenic ALV-E and SB-1 escalates it to much higher levels. This study was designed to test the impact of two new ALV-E isolates, recently derived from commercial broiler breeder flocks, in combination with the nonpathogenic SB-1 on LL-like lymphoma incidences in both an experimental egg layer line of chickens and a commercial broiler breeder line of chickens under a controlled condition. Data from this study provided an additional piece of experimental evidence on the potency of nonpathogenic ALV-E, MDV-2, and ALV-E plus MDV-2 in boosting the incidence of LL-like lymphomas in susceptible chickens. This study also generated the first piece of genomic evidence that suggests host transcriptomic variation plays an important role in modulating LL-like lymphoma formation.