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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

Differentially expressed miRNAs in response to FMDV infection. The expression patterns of 169 distinct bovine miRNAs was evaluated in serum harvested during three distinct phases of FMDV infection: a acute (viremic) b convalescent “non-carrier” and c persistently infected “carrier”. Expression levels were compared against serum from uninfected controls and are plotted onto volcano plots with the fold change in expression on the X-axis and the degree of reproducibility between replicates (p-value) on the Y-axis. Circles: miRNAs with unchanged expression, down-regulated expression (green), and up-regulated expression (red). miRNAs with significantly regulated expression (fold-change >1.5 and p-value of <0.05 [or greater than 1.25 by the –log10]) are plotted above the horizontal lines indicated on the volcano plots
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Fig2: Differentially expressed miRNAs in response to FMDV infection. The expression patterns of 169 distinct bovine miRNAs was evaluated in serum harvested during three distinct phases of FMDV infection: a acute (viremic) b convalescent “non-carrier” and c persistently infected “carrier”. Expression levels were compared against serum from uninfected controls and are plotted onto volcano plots with the fold change in expression on the X-axis and the degree of reproducibility between replicates (p-value) on the Y-axis. Circles: miRNAs with unchanged expression, down-regulated expression (green), and up-regulated expression (red). miRNAs with significantly regulated expression (fold-change >1.5 and p-value of <0.05 [or greater than 1.25 by the –log10]) are plotted above the horizontal lines indicated on the volcano plots

Mentions: Importantly, to avoid artifacts of technique, there was no pre-amplification of miRNAs prior to evaluation on the miRNA PCR arrays, which can potentially artificially increase levels of background miRNAs. By this approach, 7 bovine miRNAs were found up-regulated in serum collected from cattle acutely infected with FMDV (3–4 dpi) relative to uninfected controls. Raw scores are shown in Table 2, while volcano plots of log 2 fold changes in miRNA levels are shown in Fig. 2a. The up-regulated miRNA species included bta-miR-17-5p, bta-miR-146a, bta-miR-144, bta-miR-34a, bta-miR-369-3p, bta-miR-497, and bta-miR-22-5p (Table 2 and Fig. 2a). The three most up-regulated miRNAs were bta-miR-17-5p (+35.88 fold increase), bta-miR-146a (+34.36 fold increase), and bta-miR-144 (+28.78 fold increase) (Table 2). In contrast, three of the measured targets were significantly down-regulated during acute FMDV infection: bta-let-7 g (−1.96 fold decrease), bta-miR-1281 (−2.50 fold decrease), and bta-miR-26b (-3.09 fold decrease) (Table 2 and Fig. 2a). Some of the reported functionalities of these miRNA species are detailed in Table 2 to extrapolate for possible roles in acute FMDV infection.Table 2


Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection
Differentially expressed miRNAs in response to FMDV infection. The expression patterns of 169 distinct bovine miRNAs was evaluated in serum harvested during three distinct phases of FMDV infection: a acute (viremic) b convalescent “non-carrier” and c persistently infected “carrier”. Expression levels were compared against serum from uninfected controls and are plotted onto volcano plots with the fold change in expression on the X-axis and the degree of reproducibility between replicates (p-value) on the Y-axis. Circles: miRNAs with unchanged expression, down-regulated expression (green), and up-regulated expression (red). miRNAs with significantly regulated expression (fold-change >1.5 and p-value of <0.05 [or greater than 1.25 by the –log10]) are plotted above the horizontal lines indicated on the volcano plots
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5384155&req=5

Fig2: Differentially expressed miRNAs in response to FMDV infection. The expression patterns of 169 distinct bovine miRNAs was evaluated in serum harvested during three distinct phases of FMDV infection: a acute (viremic) b convalescent “non-carrier” and c persistently infected “carrier”. Expression levels were compared against serum from uninfected controls and are plotted onto volcano plots with the fold change in expression on the X-axis and the degree of reproducibility between replicates (p-value) on the Y-axis. Circles: miRNAs with unchanged expression, down-regulated expression (green), and up-regulated expression (red). miRNAs with significantly regulated expression (fold-change >1.5 and p-value of <0.05 [or greater than 1.25 by the –log10]) are plotted above the horizontal lines indicated on the volcano plots
Mentions: Importantly, to avoid artifacts of technique, there was no pre-amplification of miRNAs prior to evaluation on the miRNA PCR arrays, which can potentially artificially increase levels of background miRNAs. By this approach, 7 bovine miRNAs were found up-regulated in serum collected from cattle acutely infected with FMDV (3–4 dpi) relative to uninfected controls. Raw scores are shown in Table 2, while volcano plots of log 2 fold changes in miRNA levels are shown in Fig. 2a. The up-regulated miRNA species included bta-miR-17-5p, bta-miR-146a, bta-miR-144, bta-miR-34a, bta-miR-369-3p, bta-miR-497, and bta-miR-22-5p (Table 2 and Fig. 2a). The three most up-regulated miRNAs were bta-miR-17-5p (+35.88 fold increase), bta-miR-146a (+34.36 fold increase), and bta-miR-144 (+28.78 fold increase) (Table 2). In contrast, three of the measured targets were significantly down-regulated during acute FMDV infection: bta-let-7 g (−1.96 fold decrease), bta-miR-1281 (−2.50 fold decrease), and bta-miR-26b (-3.09 fold decrease) (Table 2 and Fig. 2a). Some of the reported functionalities of these miRNA species are detailed in Table 2 to extrapolate for possible roles in acute FMDV infection.Table 2

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