**7. miRNAs as potential biomarkers in herpesvirus infections**

With as many miRNAs that are expressed during each of the herpesvirus infections, the recognition of certain miRNAs are biomarkers for these infections is promising. There are a number of reasons that back the concept of miRNA biomarkers in human infections. The distinct pathophysiological events occurring during the infection is reflected in the miRNA expression patterns. For example, where miR-649 is considerably downregulated in HSV-1 infected cells as compared to the uninfected cells to mark the overwhelming participation of NF-κB is fighting the infection, there are certain miRNAs exclusively generated by the HSV (miR-H6, -H27 etc.). miRNAs are also the biomarkers of the HSV infection status within the host as certain miRNAs are specific to the lytic phase (miR-H1) whereas some are specifically expressed during the latency phase (miR-H2–6). miRNAs are easily available for detection in the body fluids such as blood, serum and human dental pulps [97, 98] and so are the v-miRNAs of the *herpesviridae* family members [99]. Although there are a few ongoing clinical studies on miRNAs biomarkers in cancer, the reports on EBV-related cancer miRNAs also being detected in the blood and urine, will boost the EBV research in the same direction [100]. Furthermore, the molecular techniques used for the miRNA detection, such as, the real-time PCR array, microarray profiling and the next-generation sequencing techniques are popular and well established in case of herpesvirus infections as well [101–104]. One of the greatest advantages of using miRNAs as biomarkers is their sustained expressions *in vivo* as compared to the mRNAs. This is because of the presence of exosomes which enclose the miRNAs. Moreover, the miRNAs released extracellularly are bound to the Ago proteins. These mechanisms protect the miRNAs against degradation by the nucleases [35, 105, 106]. Whether v-miRNAs or cellular

#### *Herpesviridae and microRNAs DOI: http://dx.doi.org/10.5772/intechopen.100370*

miRNAs are better biomarker candidates might be debatable. However, an important consideration in this context is that v-miRNAs are virus-specific whereas host miRNAs are not exclusive for a virus infection. For example, miR-155, which is crucial in HSV-1 latency is also involved in pro-inflammatory functions in other diseases such as cancer, asthma, arthritis, Cystic fibrosis and also recently reported in other viral infections, such as that of the Sars-CoV-2 [41, 107, 108]. Therefore, a panel of host and viral miRNA combinations may serve as an appropriate biomarker in case of each of the herpesvirus infection.
