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Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection

View Article: PubMed Central - PubMed

ABSTRACT

Background: Changes in the levels of circulating microRNAs (miRNAs) in the serum of humans and animals have been detected as a result of infection with a variety of viruses. However, to date, such a miRNA profiling study has not been conducted for foot-and-mouth disease virus (FMDV) infection.

Methods: The relative abundance of 169 miRNAs was measured in bovine serum collected at three different phases of FMDV infection in a proof-of-concept study using miRNA PCR array plates.

Results: Alterations in specific miRNA levels were detected in serum during acute, persistent, and convalescent phases of FMDV infection. Subclinical FMDV persistence produced a circulating miRNA profile distinct from cattle that had cleared infection. bta-miR-17-5p was highest expressed during acute infection, whereas bta-miR-31 was the highest during FMDV persistence. Interestingly, miR-1281was significantly down-regulated during both acute and persistent infection. Cattle that cleared infection resembled the baseline profile, adding support to applying serum miRNA profiling for identification of sub-clinically infected FMDV carriers. Significantly regulated miRNAs during acute or persistent infection were associated with cellular proliferation, apoptosis, modulation of the immune response, and lipid metabolism.

Conclusions: These findings suggest a role for non-coding regulatory RNAs in FMDV infection of cattle. Future studies will delineate the individual contributions of the reported miRNAs to FMDV replication, determine if this miRNA signature is applicable across all FMDV serotypes, and may facilitate development of novel diagnostic applications.

Electronic supplementary material: The online version of this article (doi:10.1186/s12985-017-0743-3) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

Cluster analysis of miRNAs differentially expressed in response to FMDV infection. Two different databases were employed to assess whether the differentially expressed miRNAs detected in this study were clustered or non-clustered: miRbase (current version) and MetaMirClust. The miRNAs found to be non-clustered were listed to the right. The miRNAs determined to be clustered were shown in circles with clustered miRNA species indicated around the circle. With the exception of bta-miR-369-3p with a cutoff of <3000 bp, the distance cutoff between miRNA sequences for the cluster analysis was set at <10,000 bp
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Fig4: Cluster analysis of miRNAs differentially expressed in response to FMDV infection. Two different databases were employed to assess whether the differentially expressed miRNAs detected in this study were clustered or non-clustered: miRbase (current version) and MetaMirClust. The miRNAs found to be non-clustered were listed to the right. The miRNAs determined to be clustered were shown in circles with clustered miRNA species indicated around the circle. With the exception of bta-miR-369-3p with a cutoff of <3000 bp, the distance cutoff between miRNA sequences for the cluster analysis was set at <10,000 bp

Mentions: Many miRNA sequences encoded in the genomes of various species have been discovered clustered with other miRNAs that often share similar regulatory functions [46, 47]. Given that, cluster analysis was performed on the differentially regulated bovine miRNAs detected in this study using two different sources: miRbase (release 21, June 2014, miRBase.org) and MetaMirClust [48]. These two databases provided corroborating data regarding whether the detected miRNAs were non-clustered or clustered, and what miRNAs clustered with them. As shown in Fig. 4, 11 of the miRNAs that were observed to be differentially regulated in the serum from cattle during FMDV infection were not clustered with other miRNAs in the Bos taurus genome. The non-clustered miRNAs included: let-7 g, bta-miR-26b, bta-miR-150, bta-miR-34a, bta-miR-146a, bta-miR-147, bta-miR-205, bta-miR-455-3p, bta-miR-1224, bta-miR-1281, and bta-miR-31. The remaining 8 miRNAs (bta-miR-497, bta-miR-144, bta-miR-181b, bta-miR-22-5p, bta-miR-23b-5p, bta-miR-17-5p, bta-miR-154a, and bta-miR-369-3p) detected in this study were found to be clustered. Of these 8, bta-miR-154a and bta-miR-369-3p were the most heavily clustered miRNAs, which is why a more stringent cluster distance was imposed of <3,000 bp apart. These two miRNAs were also the only two from this study that were clustered with each other. Similar to the genomic localization of the detected miRNAs, we concluded that there was no pattern in the clustering data.Fig. 4


Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection
Cluster analysis of miRNAs differentially expressed in response to FMDV infection. Two different databases were employed to assess whether the differentially expressed miRNAs detected in this study were clustered or non-clustered: miRbase (current version) and MetaMirClust. The miRNAs found to be non-clustered were listed to the right. The miRNAs determined to be clustered were shown in circles with clustered miRNA species indicated around the circle. With the exception of bta-miR-369-3p with a cutoff of <3000 bp, the distance cutoff between miRNA sequences for the cluster analysis was set at <10,000 bp
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Fig4: Cluster analysis of miRNAs differentially expressed in response to FMDV infection. Two different databases were employed to assess whether the differentially expressed miRNAs detected in this study were clustered or non-clustered: miRbase (current version) and MetaMirClust. The miRNAs found to be non-clustered were listed to the right. The miRNAs determined to be clustered were shown in circles with clustered miRNA species indicated around the circle. With the exception of bta-miR-369-3p with a cutoff of <3000 bp, the distance cutoff between miRNA sequences for the cluster analysis was set at <10,000 bp
Mentions: Many miRNA sequences encoded in the genomes of various species have been discovered clustered with other miRNAs that often share similar regulatory functions [46, 47]. Given that, cluster analysis was performed on the differentially regulated bovine miRNAs detected in this study using two different sources: miRbase (release 21, June 2014, miRBase.org) and MetaMirClust [48]. These two databases provided corroborating data regarding whether the detected miRNAs were non-clustered or clustered, and what miRNAs clustered with them. As shown in Fig. 4, 11 of the miRNAs that were observed to be differentially regulated in the serum from cattle during FMDV infection were not clustered with other miRNAs in the Bos taurus genome. The non-clustered miRNAs included: let-7 g, bta-miR-26b, bta-miR-150, bta-miR-34a, bta-miR-146a, bta-miR-147, bta-miR-205, bta-miR-455-3p, bta-miR-1224, bta-miR-1281, and bta-miR-31. The remaining 8 miRNAs (bta-miR-497, bta-miR-144, bta-miR-181b, bta-miR-22-5p, bta-miR-23b-5p, bta-miR-17-5p, bta-miR-154a, and bta-miR-369-3p) detected in this study were found to be clustered. Of these 8, bta-miR-154a and bta-miR-369-3p were the most heavily clustered miRNAs, which is why a more stringent cluster distance was imposed of <3,000 bp apart. These two miRNAs were also the only two from this study that were clustered with each other. Similar to the genomic localization of the detected miRNAs, we concluded that there was no pattern in the clustering data.Fig. 4

View Article: PubMed Central - PubMed

ABSTRACT

Background: Changes in the levels of circulating microRNAs (miRNAs) in the serum of humans and animals have been detected as a result of infection with a variety of viruses. However, to date, such a miRNA profiling study has not been conducted for foot-and-mouth disease virus (FMDV) infection.

Methods: The relative abundance of 169 miRNAs was measured in bovine serum collected at three different phases of FMDV infection in a proof-of-concept study using miRNA PCR array plates.

Results: Alterations in specific miRNA levels were detected in serum during acute, persistent, and convalescent phases of FMDV infection. Subclinical FMDV persistence produced a circulating miRNA profile distinct from cattle that had cleared infection. bta-miR-17-5p was highest expressed during acute infection, whereas bta-miR-31 was the highest during FMDV persistence. Interestingly, miR-1281was significantly down-regulated during both acute and persistent infection. Cattle that cleared infection resembled the baseline profile, adding support to applying serum miRNA profiling for identification of sub-clinically infected FMDV carriers. Significantly regulated miRNAs during acute or persistent infection were associated with cellular proliferation, apoptosis, modulation of the immune response, and lipid metabolism.

Conclusions: These findings suggest a role for non-coding regulatory RNAs in FMDV infection of cattle. Future studies will delineate the individual contributions of the reported miRNAs to FMDV replication, determine if this miRNA signature is applicable across all FMDV serotypes, and may facilitate development of novel diagnostic applications.

Electronic supplementary material: The online version of this article (doi:10.1186/s12985-017-0743-3) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus