*1.1. Cytomegalovirus Overview*

Cytomegalovirus (CMV) is a genus of *Herpesvirus* in the order Herpesvirales, in the family Herpesviridae, and in the subfamily Betaherpesvirinae. There are nine distinct human herpesvirus (HHV) species known to cause human diseases such as HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, HHV-6A, HHV-6B, HHV-7, HHV-8 [1,2]. Human cytomegalovirus (HCMV, HHV-5), with a double-stranded DNA genome of about 230 kb, is the most studied one among all CMV. HCMV usually causes moderate or subclinical diseases in immunocompetent adults; however, it may lead to opportunistic infections to affect individuals whose immune functions are compromised or immature [3,4]. The primary target cells of HCMV are monocytes, lymphocytes, and epithelial cells, and its major sites of latency are peripheral monocytes and CD34+ progenitor cells. HCMV infection causes

a broad range of diseases such as pneumonia, retinitis, gastrointestinal diseases, mental retardation and vascular disorders, and is a major cause of morbidity and mortality for humans [5–7]. After infection, HCMV is recurrent and competent to remain latent within the body over long periods [5,6]. In all patients, the reactivation of latent HCMV can damage tissues and lead to organ disease, and reactivated CMV may trigger indirect immunomodulatory effects to cause detrimental outcomes, including increased mortality and graft rejection of organ transplantation in recipients [8]. Furthermore, congenital infection is a major problem with HCMV in that it can result in a severe cytomegalic inclusion disease of the neonate, mucoepidermoid carcinoma, and other malignancies eventually [7,9].

### *1.2. CMV Molecular Biology*

CMV structure mainly consist of DNA core, capsid, tegument and envelope from inside to outside. The genome is complexed helically to form a DNA core, which is enclosed in a capsid composed of a total of 162 capsomere protein subunits. The capsid with a diameter of 100 nm is surrounded by the tegument. The tegument is enclosed by a lipid bilayer envelope containing viral glycoproteins to give a final diameter of about 180 nm for mature infectious viral particles (virions) [10]. The tegument compartment contains most of the viral proteins, with the most abundant one being the lower matrix phosphoprotein 65 (pp65) which is also referred as unique long 83 (UL83). The function of the tegument proteins can be classified as follows: (1) proteins that play an important role for the assembly of virions during proliferation and the disassembly of the virions during entry (structural use) and (2) proteins that modulate the host cell responses for viral infection (non-structural use) [11]. The viral envelope surrounding the tegument contains more than 20 glycoproteins that are involved in the attachment and penetration of host cells. These structural proteins include glycoprotein B, H, L, M, N, and O. CMV productive infection results in the coordinated synthesis of proteins in three overlapping phases according to the time of synthesis after infection, that is, immediate-early (0 to 2 h), early (<24 h), and late (>24 h) viral proteins which are expressed by immediate-early, early and late genes, respectively [11]. Immediately after CMV infections, the immediate early genes transcribe and ensure the transcription of early genes, which encode proteins required for the viral replication. The late genes mainly code for structural proteins.
