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In vivo expression patterns of microRNAs of Gallid herpesvirus 2 (GaHV-2) during the virus life cycle and development of Marek's disease lymphomas.

Zhao P, Li XJ, Teng M, Dang L, Yu ZH, Chi JQ, Su JW, Zhang GP, Luo J - Virus Genes (2015)

Bottom Line: The biological role of most GaHV-2 miRNAs remains unclear.According to their distinct in vivo expression patterns, the GaHV-2 miRNAs can be divided into three groups: 12 miRNAs in group I, including miR-M4-5p, displayed a typical expression pattern potentially correlated to the latent, late cytolytic, and/or the proliferative phases in the cycle of GaHV-2 pathogenesis; group II consisting of another 12 miRNAs with expression correlated to the early cytolytic and/or latent phases in GaHV-2's life cycle; while the other two miRNAs in group III showed no identical expression features.Our findings may provide meaningful clues in the search for further potential functions of viral miRNAs in GaHV-2 biology.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, People's Republic of China.

ABSTRACT
In the past decade, a large number of microRNAs (miRNAs) have been identified in the viral genome of Gallid herpesvirus 2 (GaHV-2), which is historically known as Marek's disease virus type 1. The biological role of most GaHV-2 miRNAs remains unclear. In the present study, we have performed an overall gene expression profile of GaHV-2 miRNAs during the virus life cycle at each phase of the developing disease, a highly contagious, lymphoproliferative disorder, and neoplastic immunosuppressive disease of poultry known as the Marek's disease. According to their distinct in vivo expression patterns, the GaHV-2 miRNAs can be divided into three groups: 12 miRNAs in group I, including miR-M4-5p, displayed a typical expression pattern potentially correlated to the latent, late cytolytic, and/or the proliferative phases in the cycle of GaHV-2 pathogenesis; group II consisting of another 12 miRNAs with expression correlated to the early cytolytic and/or latent phases in GaHV-2's life cycle; while the other two miRNAs in group III showed no identical expression features. Our findings may provide meaningful clues in the search for further potential functions of viral miRNAs in GaHV-2 biology.

No MeSH data available.


Related in: MedlinePlus

Expression profiles of GaHV-2 miRNAs during the different phases of the developing disease. a The Meq-clustered miRNAs; b the LAT-clustered miRNAs; c the Mid-clustered miRNAs. A quantitative real-time PCR was performed to determine miRNA expression and the absolute copy number was estimated using synthetic miR-M4-5p as the standard. Columns represent the mean miRNA expression levels in the spleens from three randomly selected birds, determined in triplicate. Error bars indicate 1× SD. The single and double stars indicate significant differences (p < 0.05 or p < 0.01) compared to that determined at 3 dpi
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Fig2: Expression profiles of GaHV-2 miRNAs during the different phases of the developing disease. a The Meq-clustered miRNAs; b the LAT-clustered miRNAs; c the Mid-clustered miRNAs. A quantitative real-time PCR was performed to determine miRNA expression and the absolute copy number was estimated using synthetic miR-M4-5p as the standard. Columns represent the mean miRNA expression levels in the spleens from three randomly selected birds, determined in triplicate. Error bars indicate 1× SD. The single and double stars indicate significant differences (p < 0.05 or p < 0.01) compared to that determined at 3 dpi

Mentions: However, distinct from the viral protein-coding genes, the GaHV-2 miRNAs could be divided into three groups with different temporal expression profiles during the progress of the disease. The expression levels of 12 viral miRNAs, including the miR-M4-5p, miR-M2-5p, miR-M2-3p, miR-M5-3p, miR-M3-3p, and miR-M12-3p in the Meq-cluster (Fig. 2a); the miR-M8-5p, miR-M8-3p, miR-M6-5p, miR-M6-3p, and miR-M7-3p in the LAT-cluster (Fig. 2b); and the miR-M11-5p in the Mid-cluster (Fig. 2c) increased and reached a first peak at 14–21 dpi, decreased by 30 dpi, and were then highly expressed again at 45–60 dpi. These miRNAs constitute the first group and they displayed an expression pattern that may be closely correlated to the latent, late cytolytic, and/or the proliferative phases in MD pathogenesis. One of the highest expressed GaHV-2 miRNAs, miR-M4-5p, has been characterized as a functional miR-155 ortholog [18], and deletion of miR-M4 from the viral genomes of the virulent (v) GaHV-2 strain pRB-1B5 and the very virulent GaHV-2 strain GX0101 significantly decrease their oncogenicity [20, 21]. In addition to the previously reported conserved cellular genes targeted by cellular miR-155 [28], we have shown recently that miR-M4-5p down-regulates the expression of the latent transforming growth factor-β (TGF-β)-binding protein 1 (LTBP1). This leads to a significant decrease in activation and secretion of TGF-β1, with concomitant suppression of TGF-β signaling and a significant increase in the level of expression of c-MYC, a well-known oncogene which is critical for the virally induced tumorigenesis [29]. In addition to its involvement in GaHV-2 oncogenesis, miR-M4-5p has also been shown to specifically inhibit the production of UL28 [19], a viral protein homologous to a human herpesvirus 1 (HHV-1) protein involved in the cleavage/packaging of viral DNA. These facts help to explain the expression pattern of miR-M4-5p during GaHV-2’s life cycle and in particular its higher expression level during the late stages of the developing disease. The other 11 miRNAs of group I displayed expression patterns similar to that of miR-M4-5p. We have recently shown that in addition to miR-M4-5p, deletions of the other individual Meq-clustered miRNAs, i.e., miR-M2, miR-M3, and miR-M12, also variably decrease the pathogenicity and oncogenicity of the virus [30]. Thus, whether or not these miRNAs encoded in the Meq or other two clusters play a similar part in the virus life cycle remains to be further studied.Fig. 2


In vivo expression patterns of microRNAs of Gallid herpesvirus 2 (GaHV-2) during the virus life cycle and development of Marek's disease lymphomas.

Zhao P, Li XJ, Teng M, Dang L, Yu ZH, Chi JQ, Su JW, Zhang GP, Luo J - Virus Genes (2015)

Expression profiles of GaHV-2 miRNAs during the different phases of the developing disease. a The Meq-clustered miRNAs; b the LAT-clustered miRNAs; c the Mid-clustered miRNAs. A quantitative real-time PCR was performed to determine miRNA expression and the absolute copy number was estimated using synthetic miR-M4-5p as the standard. Columns represent the mean miRNA expression levels in the spleens from three randomly selected birds, determined in triplicate. Error bars indicate 1× SD. The single and double stars indicate significant differences (p < 0.05 or p < 0.01) compared to that determined at 3 dpi
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Expression profiles of GaHV-2 miRNAs during the different phases of the developing disease. a The Meq-clustered miRNAs; b the LAT-clustered miRNAs; c the Mid-clustered miRNAs. A quantitative real-time PCR was performed to determine miRNA expression and the absolute copy number was estimated using synthetic miR-M4-5p as the standard. Columns represent the mean miRNA expression levels in the spleens from three randomly selected birds, determined in triplicate. Error bars indicate 1× SD. The single and double stars indicate significant differences (p < 0.05 or p < 0.01) compared to that determined at 3 dpi
Mentions: However, distinct from the viral protein-coding genes, the GaHV-2 miRNAs could be divided into three groups with different temporal expression profiles during the progress of the disease. The expression levels of 12 viral miRNAs, including the miR-M4-5p, miR-M2-5p, miR-M2-3p, miR-M5-3p, miR-M3-3p, and miR-M12-3p in the Meq-cluster (Fig. 2a); the miR-M8-5p, miR-M8-3p, miR-M6-5p, miR-M6-3p, and miR-M7-3p in the LAT-cluster (Fig. 2b); and the miR-M11-5p in the Mid-cluster (Fig. 2c) increased and reached a first peak at 14–21 dpi, decreased by 30 dpi, and were then highly expressed again at 45–60 dpi. These miRNAs constitute the first group and they displayed an expression pattern that may be closely correlated to the latent, late cytolytic, and/or the proliferative phases in MD pathogenesis. One of the highest expressed GaHV-2 miRNAs, miR-M4-5p, has been characterized as a functional miR-155 ortholog [18], and deletion of miR-M4 from the viral genomes of the virulent (v) GaHV-2 strain pRB-1B5 and the very virulent GaHV-2 strain GX0101 significantly decrease their oncogenicity [20, 21]. In addition to the previously reported conserved cellular genes targeted by cellular miR-155 [28], we have shown recently that miR-M4-5p down-regulates the expression of the latent transforming growth factor-β (TGF-β)-binding protein 1 (LTBP1). This leads to a significant decrease in activation and secretion of TGF-β1, with concomitant suppression of TGF-β signaling and a significant increase in the level of expression of c-MYC, a well-known oncogene which is critical for the virally induced tumorigenesis [29]. In addition to its involvement in GaHV-2 oncogenesis, miR-M4-5p has also been shown to specifically inhibit the production of UL28 [19], a viral protein homologous to a human herpesvirus 1 (HHV-1) protein involved in the cleavage/packaging of viral DNA. These facts help to explain the expression pattern of miR-M4-5p during GaHV-2’s life cycle and in particular its higher expression level during the late stages of the developing disease. The other 11 miRNAs of group I displayed expression patterns similar to that of miR-M4-5p. We have recently shown that in addition to miR-M4-5p, deletions of the other individual Meq-clustered miRNAs, i.e., miR-M2, miR-M3, and miR-M12, also variably decrease the pathogenicity and oncogenicity of the virus [30]. Thus, whether or not these miRNAs encoded in the Meq or other two clusters play a similar part in the virus life cycle remains to be further studied.Fig. 2

Bottom Line: The biological role of most GaHV-2 miRNAs remains unclear.According to their distinct in vivo expression patterns, the GaHV-2 miRNAs can be divided into three groups: 12 miRNAs in group I, including miR-M4-5p, displayed a typical expression pattern potentially correlated to the latent, late cytolytic, and/or the proliferative phases in the cycle of GaHV-2 pathogenesis; group II consisting of another 12 miRNAs with expression correlated to the early cytolytic and/or latent phases in GaHV-2's life cycle; while the other two miRNAs in group III showed no identical expression features.Our findings may provide meaningful clues in the search for further potential functions of viral miRNAs in GaHV-2 biology.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, People's Republic of China.

ABSTRACT
In the past decade, a large number of microRNAs (miRNAs) have been identified in the viral genome of Gallid herpesvirus 2 (GaHV-2), which is historically known as Marek's disease virus type 1. The biological role of most GaHV-2 miRNAs remains unclear. In the present study, we have performed an overall gene expression profile of GaHV-2 miRNAs during the virus life cycle at each phase of the developing disease, a highly contagious, lymphoproliferative disorder, and neoplastic immunosuppressive disease of poultry known as the Marek's disease. According to their distinct in vivo expression patterns, the GaHV-2 miRNAs can be divided into three groups: 12 miRNAs in group I, including miR-M4-5p, displayed a typical expression pattern potentially correlated to the latent, late cytolytic, and/or the proliferative phases in the cycle of GaHV-2 pathogenesis; group II consisting of another 12 miRNAs with expression correlated to the early cytolytic and/or latent phases in GaHV-2's life cycle; while the other two miRNAs in group III showed no identical expression features. Our findings may provide meaningful clues in the search for further potential functions of viral miRNAs in GaHV-2 biology.

No MeSH data available.


Related in: MedlinePlus