Marek's disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells

Niikura, Masahiro; Kim, Taejoong; Hunt, Henry D.; Burnside, Joan; Morgan, Robin; Dodgson, Jerry B.; Cheng, Hans H.

doi:10.1016/j.virol.2006.09.010

Cited by 45 publications

(28 citation statements)

References 38 publications

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“…MDV generated from rMd5-B40 have virulence identical to the Md5 strain field isolate [14] and the complete nucleotide sequence of (A) Week post inoculation rMd5-B40 BAC has been obtained (manuscript in preparation). R-LORF10 and LORF4 were selected as targets due to their interaction with MHC class II b and Ii chain, respectively, and the observation that MHC class II is specifically upregulated on the cell surface of MDVinfected cells [8].…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, R-LORF10 and LORF4 were found to interact with MHC class II b chain and Ii (invariant or c) chain, respectively [7]. Interestingly, unlike all other herpesviruses, MDV upregulates MHC class II cell surface expression in infected cells [8]. This novel result implies that MDV may use these interactions to target viral infection or enhance the spread to CD4?…”

Section: Introductionmentioning

confidence: 95%

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Marek’s disease viruses lacking either R-LORF10 or LORF4 have altered virulence in chickens

2010

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The Marek's disease virus (MDV, Gallid herpesvirus 2) genome encodes approximately 110 open reading frames (ORFs). Many of these ORFs are annotated based purely on homology to other herpesvirus genes, thus, direct experiments are needed to verify the gene products, especially the hypothetical or MDV-specific ORFs, and characterize their biological function, particularly with respect to pathogenicity in chickens. Previously, a comprehensive two-hybrid assay screen revealed nine specific chicken-MDV protein-protein interactions. In order to characterize the role of hypothetical MDV proteins R-LORF10 and LORF4, which were shown to interact with major histocompatibility complex (MHC) class II beta chain and Ii (invariant or gamma) chain, respectively, recombinant MDVs derived from virulent MDV-BAC clone rMd5-B40 were generated. Recombinant MDV rMd5DeltaR-LORF10 lacked part of the promoter and the first 17 amino acids in both copies of R-LORF10, and rMd5mLORF4 had point mutations in LORF4 that disrupted the start codon and introduced a premature stop codon without altering the amino acid sequence of overlapping ORF UL1, which encodes glycoprotein L (gL). Mutations in either R-LORF10 or LORF4 neither prevent MDV reconstitution from modified MDV-BACs nor significantly alter virus growth rate in vitro. However, MDV generated from rMd5DeltaR-LORF10 had reduced virulence compared to the parental MDV. Surprisingly, MDV with the LORF4 mutations had significantly higher overall MD incidence as measured by mortality, tumor production, and MD symptoms in infected chickens. These results indicate R-LORF10 and LORF4 encode real products, and are involved in MDV virulence although their mechanisms, especially with respect to modulation of MHC class II cell surface expression, are not clearly understood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Marek’s disease viruses lacking either R-LORF10 or LORF4 have altered virulence in chickens

2010

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“…Electron-microscopy studies of the MDV genome provided the first evidence that this double-stranded DNA virus possesses repeat structures that are characteristic of alphaherpesviruses, which was confirmed by detailed restriction-enzyme mapping and sequencing, first of individual genes, and, later, of the en-tire genome (Osterrieder et al, 2006). In addition, unlike the majority of herpesviruses, MDV up-regulates MHC class II cell surface expression in infected cells both in vitro and in vivo (Niikura et al, 2007). Recent advances in our knowledge of MDV genetics and functional genomics have dramatically increased our understanding of the mechanisms leading to latency and tumor formation.…”

Section: Introductionmentioning

confidence: 87%

Heat-shock protein 70 is associated with the entry of Marek΄s disease virus into fibroblast

Wang¹

2011

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Summary. -Literature pertaining to the interactions between Marek΄s disease virus (MDV) entry-related glycoproteins and corresponding receptors is still limited. Results from a Western blot analysis of cellular proteins for virus receptors and co-immunoprecipitation suggest that heat shock protein 70 (HSP70) is a potential cellular receptor for MDV glycoprotein gH. Plaque inhibition assays confirm the involvement of HSP70 in the early stages of MDV entry into chicken embryo fibroblasts (CEF). The present work supports that HSP70 is implicated in the MDV entry process by binding to gH, and enhances the understanding of multifunctional HSP70 and the MDV infection process.

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“…Another justification is that given the large volume of data produced by genomics, each method provides an additional screen to limit the number of targets to verify and characterise in future experiments. Efforts to experimentally characterise growth hormone (Liu et al 2001), stem-cell antigen 2 (Mao et al 2010), and major histocompatibility complex class II b chain (Niikura et al 2007) validated their corresponding genes as influencing genetic resistance to MD.…”

Section: Introductionmentioning

confidence: 99%

Chicks and single-nucleotide polymorphisms: an entrée into identifying genes conferring disease resistance in chicken

Cheng

MacEachern²,

Subramaniam

et al. 2012

Anim. Prod. Sci.

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Abstract. Marek's disease (MD) is one of the most serious chronic infectious disease threats to the poultry industry worldwide. Selecting for increased genetic resistance to MD is a control strategy that can augment current vaccinal control measures. Although our previous efforts integrating various genomic screens successfully identified three resistance genes, the main limitation was mapping precision, which hindered our ability to identify and further evaluate highconfidence candidate genes. Towards identifying the remaining genes of this complex trait, we incorporated three additional approaches made substantially more powerful through next-generation sequencing and that exploit the growing importance of expression variation. First, we screened for allele-specific expression (ASE) in response to Marek's disease virus (MDV) infection, which, when allelic imbalance was identified, is sufficient to indicate a cisacting element for a specific gene. Second, sequencing of genomic regions enriched by chromatin immunoprecipitation (ChIP) combined with transcript profiling identified motifs bound and genes directly regulated by MDV Meq, a bZIP transcription factor and the viral oncogene. Finally, analysis of genomic sequences from two experimental lines divergently selected for MD genetic resistance allowed inference about regions under selection as well as potential causative polymorphisms. These new combined approaches have resulted in a large number of high-confidence genes conferring MD resistance reflecting the multigenic basis of this trait, which expands our biological knowledge and provides corresponding single-nucleotide polymorhpisms (SNPs) that can be directly evaluated for their genetic contribution towards disease resistance.

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Marek's disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells

Cited by 45 publications

References 38 publications

Marek’s disease viruses lacking either R-LORF10 or LORF4 have altered virulence in chickens

Marek’s disease viruses lacking either R-LORF10 or LORF4 have altered virulence in chickens

Heat-shock protein 70 is associated with the entry of Marek΄s disease virus into fibroblast

Chicks and single-nucleotide polymorphisms: an entrée into identifying genes conferring disease resistance in chicken

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