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Whole blood microRNA profiles in adenovirus-infected children


Adenovirus causes acute self-limited illnesses including respiratory infections, gastroenteritis and conjunctivitis in children. microRNAs (miRs) are small non-coding RNAs that post-transcriptionally regulate genes associated with immune response and inflammation. A miR profile was created to understand the role of miRs in modulating the host response to adenovirus infection. Total RNA extracted from whole blood of 6 acute adenovirus-infected children and 12 healthy controls were analyzed by small RNA sequencing. The top 5 differentially expressed miRs (miRs- 3614-5p, -16, -15a, 126* and -126 (nominal p-value < 0.05)) were elevated in adenovirus-infected children. These miRs were then tested by qRT-PCR in the whole blood of an independent cohort of children infected with adenovirus (n=24) and healthy controls (n=24). miR-3614-5p was validated as being significantly differentially expressed and was subjected to pathway analysis to reveal predicted gene targets. The top 5 predicted gene targets were cross referenced with previously analyzed Lymphochip microarray data sets, which revealed POU2F1 to be down- regulated in adenovirus-infected patients. POU2F1, however, was not validated in an independent cohort by qRT-PCR. Sequencing of small RNA allowed discovery of miRs that may participate in host defense of adenovirus infection. miR- 3614-5p was shown to be differentially expressed. POU2F1 is a predicted target of miR-3614-5p, which is an important transcription factor that increases inflammation by regulating iNOS, E-selectin and VCAM in the host as a mechanism to limit adenovirus replication. Failure to demonstrate down-regulation of the transcription factor POU2F1 may be due to timing of sample collection from these patients

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