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

Mays, Jody K.; Black-Pyrkosz, Alexis; Mansour, Tamer; Schutte, Brian C.; Chang, Shuang; Dong, Kunzhe; Hunt, Henry D.; Fadly, A. M.; Zhang, Lei; Zhang, Huanmin

doi:10.1128/jvi.00861-19

Cited by 15 publications

(24 citation statements)

References 77 publications

(97 reference statements)

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“…Furthermore, recent work has shown interactions between ALVEs and the increasingly virulent Marek's Disease Virus (MDV), a chicken-specific alphaherpesvirus. MDV can induce ALVE expression, even of normally silenced elements such as ALVE1 [32,33], and MDV vaccines can induce higher incidence of spontaneous lymphoid tumours in lines containing ALVE21 [34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterisation of endogenous Avian Leukosis Virus subgroup E (ALVE) insertions in chicken whole genome sequencing data

et al. 2020

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Background: Endogenous retroviruses (ERVs) are the remnants of retroviral infections which can elicit prolonged genomic and immunological stress on their host organism. In chickens, endogenous Avian Leukosis Virus subgroup E (ALVE) expression has been associated with reductions in muscle growth rate and egg production, as well as providing the potential for novel recombinant viruses. However, ALVEs can remain in commercial stock due to their incomplete identification and association with desirable traits, such as ALVE21 and slow feathering. The availability of whole genome sequencing (WGS) data facilitates high-throughput identification and characterisation of these retroviral remnants. Results: We have developed obsERVer, a new bioinformatic ERV identification pipeline which can identify ALVEs in WGS data without further sequencing. With this pipeline, 20 ALVEs were identified across eight elite layer lines from Hy-Line International, including four novel integrations and characterisation of a fast feathered phenotypic revertant that still contained ALVE21. These bioinformatically detected sites were subsequently validated using new highthroughput KASP assays, which showed that obsERVer was highly precise and exhibited a 0% false discovery rate. A further fifty-seven diverse chicken WGS datasets were analysed for their ALVE content, identifying a total of 322 integration sites, over 80% of which were novel. Like exogenous ALV, ALVEs show site preference for proximity to protein-coding genes, but also exhibit signs of selection against deleterious integrations within genes. Conclusions: obsERVer is a highly precise and broadly applicable pipeline for identifying retroviral integrations in WGS data. ALVE identification in commercial layers has aided development of high-throughput diagnostic assays which will aid ALVE management, with the aim to eventually eradicate ALVEs from high performance lines. Analysis of non-commercial chicken datasets with obsERVer has revealed broad ALVE diversity and facilitates the study of the biological effects of these ERVs in wild and domesticated populations.

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Section: Introductionmentioning

confidence: 99%

Identification and characterisation of endogenous Avian Leukosis Virus subgroup E (ALVE) insertions in chicken whole genome sequencing data

et al. 2020

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“…ALVEs exhibit the canonical retroviral structure without accessory genes, and have shorter long terminal repeats (LTRs) than exogenous ALVs, rendering them slow-transformers [ 3 ]. ALVEs remain of interest to both industry and academia for their impact on poultry characteristics [ 4 , 5 ], historical negative associations with productivity traits [ 6 , 7 ], and the complex interactions with exogenous viruses, including ALV [ 8 , 9 ] and non-retroviruses, such as Marek’s Disease virus (MDV) [ 10 ]. The current chicken reference genome (GRCg6a), notably derived from a modern red junglefowl (the pre-domesticated ancestor of chickens), contains two ALVEs [ 11 ].…”

Section: Main Textmentioning

confidence: 99%

“…Using cell lines, they then observed reductions in ALVE expression when cells were infected with the retroviruses ALVJ and reticuloendotheliosis virus, but increased expression when infected with the herpesvirus MDV, particularly of ALVE envelope transcripts. When viruses are so commonly studied in isolation, this work showing modified expression during effective co-infection is of particular interest, especially given recent work on MDV vaccination and elevated incidence of spontaneous lymphoid-like tumours [ 10 ]. However, the authors attribute all ALVE expression specifically to ALVE1, without confirming its presence in the genome.…”

Section: Main Textmentioning

confidence: 99%

Falling fowl of the chicken reference genome: pitfalls of studying polymorphic endogenous retroviruses

Mason

2021

Retrovirology

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High quality reference genomes have facilitated the study of endogenous retroviruses (ERVs). However, there are an increasing number of published works which assume the ERVs in reference genomes are universal; even those of evolutionarily recent integrations. Consequently, these studies fail to properly characterise polymorphic ERVs, and even propose biological functions for ERVs that may not actually be present in the genomes of interest. Here, I outline the pitfalls of three studies of chicken endogenous Avian Leukosis Viruses (ALVEs or “ev genes”: the “original” ERVs), all confounded by the assumption that the reference genome provides a representative ALVE baseline.

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“…A similar but different lymphoma in chicken is known as avian lymphoid leukosis-like (LL-like) lymphoma. LL-like lymphoma has been reported in chicken flocks with the characteristics of no exogenous ALV to be found [ 9 – 11 ]. Reported cases of avian lymphoid leukosis-like lymphoma incidences in the susceptible chickens are relatively low, but the apathogenic subgroup E avian leukosis virus (ALV-E) and the Marek’s disease vaccine, SB-1, significantly escalate the LL-like lymphoma incidence in the susceptible chickens [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

A comprehensive analysis of avian lymphoid leukosis-like lymphoma transcriptomes including identification of LncRNAs and the expression profiles

et al. 2022

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Avian lymphoid leukosis-like (LL-like) lymphoma has been observed in some experimental and commercial lines of chickens that are free of exogenous avian leukosis virus. Reported cases of avian lymphoid leukosis-like lymphoma incidences in the susceptible chickens are relatively low, but the apathogenic subgroup E avian leukosis virus (ALV-E) and the Marek’s disease vaccine, SB-1, significantly escalate the disease incidence in the susceptible chickens. However, the underlying mechanism of tumorigenesis is poorly understood. In this study, we bioinformatically analyzed the deep RNA sequences of 6 lymphoid leukosis-like lymphoma samples, collected from susceptible chickens post both ALV-E and SB-1 inoculation, and identified a total of 1,692 novel long non-coding RNAs (lncRNAs). Thirty-nine of those novel lncRNAs were detected with altered expression in the LL-like tumors. In addition, 13 lncRNAs whose neighboring genes also showed differentially expression and 2 conserved novel lncRNAs, XLOC_001407 and XLOC_022595, may have previously un-appreciated roles in tumor development in human. Furthermore, 14 lncRNAs, especially XLOC_004542, exhibited strong potential as competing endogenous RNAs via sponging miRNAs. The analysis also showed that ALV subgroup E viral gene Gag/Gag-pol and the MD vaccine SB-1 viral gene R-LORF1 and ORF413 were particularly detectable in the LL-like tumor samples. In addition, we discovered 982 novel lncRNAs that were absent in the current annotation of chicken genome and 39 of them were aberrantly expressed in the tumors. This is the first time that lncRNA signature is identified in avian lymphoid leukosis-like lymphoma and suggests the epigenetic factor, lncRNA, is involved with the avian lymphoid leukosis-like lymphoma formation and development in susceptible chickens. Further studies to elucidate the genetic and epigenetic mechanisms underlying the avian lymphoid leukosis-like lymphoma is indeed warranted.

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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

Cited by 15 publications

References 77 publications

Identification and characterisation of endogenous Avian Leukosis Virus subgroup E (ALVE) insertions in chicken whole genome sequencing data

Identification and characterisation of endogenous Avian Leukosis Virus subgroup E (ALVE) insertions in chicken whole genome sequencing data

Falling fowl of the chicken reference genome: pitfalls of studying polymorphic endogenous retroviruses

A comprehensive analysis of avian lymphoid leukosis-like lymphoma transcriptomes including identification of LncRNAs and the expression profiles

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