Cytomegalovirus (CMV) is also known as human herpesvirus-5 (HHV-5) and is a double-stranded deoxyribonucleic acid DNA virus that consists of a 235 kb long genome that belongs to the Herpesviridae family and is an icosahedral capsid enveloped in shape (Yu et al., 2017). Infected people are divided into symptomatic and asymptomatic groups for therapeutic purposes; symptomatic individuals are usually immunocompromised, and individuals with asymptomatic infection are usually in good health, even though asymptomatic individuals do not show the clinical phenotype of the infection as symptomatic individuals. However, these two species have similar genetic expression profiles (Mohit and Mahmoud, 2023) (Ouellette et al., 2020). Patients infected with symptomatic CMV usually suffer from fever, sore throat, fatigue, and swollen glands, and infection may cause infectious mononucleosis and hepatitis, which are similar clinical features to those of the Epstein–Barr virus, which is a member of the same virus family (CDC, 2020). In severely immunocompromised individuals, CMV can cause damage to the central nervous system, causing encephalitis, myelitis, and myeloradiculitis (Tselis, 2014).
Infection with CMV is not restricted by age or sex, even though the main risk factors for CMV infection are fluid contact with infected individuals, where it can be transmitted through milk feeding and delivery in the case of congenital CMV infection and other fluids, such as urine, saliva, blood and blood, or through transplantation (CDC, 2020). CMV retransplantation can occur due to the entry of CMV into a latent phase in which the virus remains dormant in infected cells until it is donated to a patient, which may lead to the activation of latent CMV. Additionally, CMV can reactivate in immunocompromised situations, such as AIDS, chemotherapy or nutrient deficiency (CDC, 2020). Cytomegalovirus is usually a mild infection, but in the case of a compromised immune individual, the rate of virus replication reaches a high level, causing serious end-organ disease since CMV can infect a wide range of epithelial and fibroblasts (Griffiths and Reeves, 2021). CMV introduces its genome to host cells by inducing PH-independent fusion, during which the virus enters without its envelope inside a fibroblast. Additionally, CMV can induce endocytosis, during which the whole virus enters an epithelial cell with its envelope (Griffiths and Reeves, 2021). The CMV envelope contains glycoprotein M, glycoprotein N, glycoprotein B, glycoprotein H, UL130, and UL131, which work to induce platelet-derived growth factor-α (PDGFRα), epidermal growth factor receptor (EGFR), heparan sulfate proteoglycans (HSPGs) and integrins (Griffiths and Reeves, 2021).
Congenital Cytomegalovirus (CMV) is an infectious condition in which infants are infected with CMV through their mothers; they are usually unaware of their infectious condition before delivery, which leads to congenital defects in the developing brain (CDC, 2020). Not all infected babies show signs and symptoms of CMV; however, some infected conditions are symptomatic and show signs at birth, such as jaundice, rash, low birth weight, hepatosplenomegaly, and retinitis, and some of them experience seizure episodes. These signs can lead to long-term health problems, including vision loss, motor development delay, microcephaly, seizures, and hearing loss (CDC, 2020). Tegument proteins are proteins that exist in the space between the virus capsid and its envelope in all herpesviruses (Hyun et al., 2017). Treatment for CMV can be administered in the case of symptomatic congenital cytomegalovirus in the form of drugs such as valganciclovir to improve the development outcome (CDC, 2020).
Epilepsy (EP) is a neurological noncontagious disorder of the central nervous system (CNS) caused by repetitive uncontrolled electric rushes in the whole brain or in part leading to unintended or involuntary movements (WHO, 2023). There are 50 million people affected by epilepsy, which is considered to be the most common neurological disorder worldwide (WHO, 2023). Epilepsy is classified into two main categories: focal seizures and generalized seizures, where focal seizures involve specific involuntary movements of the body part. In contrast, generalized seizures involve the whole body (WHO, 2023). Essentially, epilepsy is not restricted by specific age or sex; however, the effect of seizure episodes may vary between males and females, where males generally experience more severe seizure episodes, while women experience more seizure fluctuations (Reddy et al., 2021). Epileptic patients develop symptoms such as loss of consciousness, awareness, disturbances in movement, and loss of vision; additionally, they tend to experience physical injuries because of sudden involuntary movements, which may lead to fractures and bruising, which can cause psychological problems (WHO, 2023). The incidence of EP in Arab countries is 6.9 per 1000 individuals, with the leading risk factors being parental consanguinity and family history (Idris et al., 2021). Clinical manifestations and electroencephalography (EEG) images are used to diagnose epilepsy caused by different etiologies, such as trauma or damage in the brain; congenital abnormalities; encephalitis; and brain tumors, such as gliomas (WHO, 2023). Genetic variance and mutations play a role in activating seizures, for example, UBE3A, CDKL5, and genes that encode ion channels in neurons, such as KCNQ2 (Samanta, 2020, 2021) (Alejandro, 2022). Infectious agents may cause epilepsy to develop by inducing inflammatory-mediated agent responses in brain tissue to affect cytokine secretion, leading to hyperexcitability (Vezzani et al., 2016). Generally, epilepsy is caused by an error in neurotransmitter receptors such as NMDA and GABA, which enhance or inhibit the electrical signals that may lead to seizure episodes (Kapur, 2018). People who have epilepsy are treated with surgery in cases of focal seizure or with antiepileptic drugs such as oxcarbazepine and carbamazepine for focal and generalized epilepsy, respectively, which are selected based on patient clinical history (Kanner and Bicchi, 2022).
There is notable evidence of the involvement of cytomegalovirus in epilepsy (Corazzi et al., 2024) (O’Brien et al., 2022). For example, Lin et al studied 112 neurological patients from January 2012 to December 2014, and the results showed that 96 patients with epilepsy had the expression of the pp67 mRNA of CMV. Another study conducted magnetic resonance imaging (MRI) on patients who had symptomatic congenital CMV. The results showed that the second most abnormal finding on MRI was polymicrogyria, which is related to epilepsy (Kwak et al., 2018). Overall, previous studies have shown that there is an association between cytomegalovirus infection and epilepsy, but the exact pathogenesis is still unclear. This study aimed to investigate the molecular crosstalk between Cytomegalovirus and epilepsy via transcriptomic and biological network approaches.