hepatitis C virus (HCV) shows a unique connection with miR-122, abundantly expressed in the liver, which primes the environment for efficient virus proliferation and persistence within the host [6]. In particular, large DNA viruses such as herpes simplex virus 1 (HSV-1) have been found to encode their miRNAs, in addition to exploiting those of the host [7; 8; 9]. HSV-1 is a widespread human pathogen known as the causative agent of cold sores. In rare cases, HSV-1 can also cause life-threatening infections and diseases such as encephalitis [10]. The primary site of infection is usually mucosal epithelium, where the virus enters the cells and abundantly expresses its genes in a controlled cascade of gene expression, first immediate-early (IE), early (E), and late proteins (L), finally leading to the generation of new virions. Additionally, HSV-1 can infect nearby innervating sensory neurons and travel retrogradely from the peripheral axons to the neuronal body to establish lifelong latent infection. In contrast to the productive infection, during latency, the virus does not replicate and the only abundantly expressed transcripts are those arising from the latency-associated transcript (LAT) locus, which gives rise to stable long non-coding RNAs (lncRNA) called LAT intron, and a number of microRNAs [11]. Occasionally, HSV-1 can reactivate and travel anterogradely to the periphery to re-enter the productive phase of infection and spread [10]. HSV-1 has been shown to express 29 mature miRNAs (vmiRNAs), all of which can be detected, at various levels, during the productive phase of infection. However, only a small subset of vmiRNAs has been detected in latently infected human neurons [12; 13] or latency models [14]. This includes vmiRNAs arising from the LAT region (miR-H2, -H3, -H4, -H5, -H7, and -H8) and miRNAs located just upstream of the LAT transcription start site (miR-H1 and miR-H6). The exact roles of vmiRNAs in HSV-1 infection are yet to be revealed, nonetheless, for some, a role in the control of latency had been demonstrated [11; 15; 16; 17; 18; 19]. On the other hand, several studies have reported the deregulation of host miRNAs after HSV-1 infection [20], and for some, their functional importance has been proposed. For example, miR-23a, miRNA upregulated after HSV-1 infection, decreases the levels of interferon regulatory transcription factor 1 (IRF1), which in turn results in reduced levels of viperin, an important anti-viral gene, and thus facilitates virus infection [21; 22]. Likewise, it has been shown that miR-132 is induced in the KSHV infection of lymphatic endothelial cells (LECs) as well as HSV-1 or HCMV infection of monocytes and it targets p300, a protein that associates with CREB and is an important mediator of antiviral immunity. By decreasing the levels of p300, the expression of IFN-\(\beta\), IgG15, IL-1\(\beta\), and IL6 is impaired, resulting in the suppression of antiviral immunity, thus facilitating viral replication [23]. Interestingly, miR-138, which is abundantly present in neurons, limits the expression of ICP0, an important IE viral protein crucial for efficient reactivation, thereby repressing the productive cycle and promoting latency in mice [24]. Additionally, miR-138 has been found to decrease the expression of host genes important for virus replication, transcription factors Oct-1 and FoxC1, to create a suitable environment for latent infection [25]. The miRNA cluster miR-183/96/182, which is transcribed as a single pri-miRNA transcript and further processed into three separate pre-miRNAs, has been shown to be deregulated in cells infected with different herpesviruses including HSV-1, human cytomegalovirus (HCMV), and Epstein-Barr virus (EBV) [26; 27; 28]. In HSV-1 infected cells, this cluster, which is suppressed by host protein ZEB, is regulated by ICP0, which directs the host protein ZEB for ubiquitin-dependent proteasomal degradation, which in turn leads to the de-repression of the miR-183/96/182 cluster [29]. However, the biological relevance of this deregulation is not known.