Tehran University Medical Journal

Background: In the last 10 years, co-infection of human immunodeficiency virus/human T-cell leukemia virus-1 (HIV/HTLV-1) has emerged as a worldwide health problem. These viruses has the same route to infect human but different effects on CD4 positive T-cells. There was controversial results about the influence of co-infection HIV/HTLV-1 pathogenesis. This study compared clinical course and laboratory findings in HIV/HTLV-1 co-infection with HIV mono infection.
Methods: This historical cohort study carried in Mashhad Consultation Center of Infective and Behavior Diseases, Mashhad, Iran, from April 2013 to march 2017. Persons who referred evaluated by the enzyme-linked immunosorbent assay (ELISA), then patients with positive ELISA test rechecked by ELISA and Western blot. Platelet count, WBC count, neutrophils count, positive CD4 T-cells, staging and disease severity evaluated at diagnosis, in starting and after of antiretroviral therapy in mono and co-infected patients. Demographic characteristics, including age, educational level, occupational state, marriage situation, past medical history and high-risk behaviors were extracted from the files.
Results: Of 64 patients enrolled in this study, 61 persons were male. Of 64 participants patients, 42 persons were infected with HIV (35 persons of them were positive for hepatitis C virus), other 22 positive HIV cases, were co infected by HTLV-1 too (18 persons were positive for hepatitis C virus (HCV). Co infected patients had more history of high-risk situations specially intravenous drug abuse. The most common opportunistic infections was cryptogenic tuberculosis (TB), candidiasis and military TB. Opportunistic infections and lab findings (except for CD4 positive T-cell) were the same in both group. Clinical severity and disease staging did not differ significantly between two groups. Death was more common in co-infected group.
Conclusion: Clinical course in human T-cell leukemia virus-1 (HTLV-1) co-infection has not obvious differences with previously HIV patients compare with only HIV infected patients. In co-infection with the onset of treatment the increase in the level of CD4 positive cells was higher than that HIV infection.

Background: The Multi state Markov models have extensively application with categorization of laboratory marker of CD4 cells for evaluation of HIV disease progression. These models with different states result in different effects of covariates and prediction of HIV disease trend. The main purpose of this study was comparison of four and five states models with the three- state in order to select the model with better prediction ability of occurrence of HIV and finally death in HIV positive people.
Methods: A total of 305 HIV positive people were included in this cohort study in the Iran AIDS center in Imam Khomeini Hospital in Tehran that entered during March 1995 to January 2005 and then fallowed up to October 2014. The three continuous- time Markov models of three-, four- and five- state models were fitted to data to describe the evolution of a HIV disease Trend over different states.
For comparison of models, two criteria of modification of Akaike’s criterion (DRAIC) and likelihood cross-validation criterion (DRLCV) along with their 95% tracking interval was used. For fitting of these models and estimation of transition matrix and the hazard ratio of gender and treatment independent variables, the msm package of R project for statistical computing, version R 3.2.4 (www.r-project.org) was used.
Results: The results showed that the four- state model has more prediction ability than five-state model for evaluation of HIV disease Trend. In the four-state model, the progression hazard ratio to death for people who received highly active antiretroviral therapy (HAART) was 0.64 lower than who didn’t get this therapy. Moreover, the progression hazard ratio for men was 2.33 fold in comparison to women. The disease progression hazard ratio to death was 4.9 fold for men in comparison to women.
Conclusion: The (DRAIC) and (DRLCV) criterions showed that the four-state model has more predictive ability of the progression trend of HIV disease in comparison of five-state model.

Background: Scleroderma is a chronic systemic disorder that affects the connective tissues. It is characterized by several immune manifestations, inflammation, vascular damage, and fibrosis. Some of the viral infections with complex mechanisms are involved in the development and progression of many autoimmune diseases, such as scleroderma. The present study aimed to investigate the serological prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) infections in Iranian patients with scleroderma.
Methods: In this descriptive study 65 patients with scleroderma and 65 healthy individuals who had no autoimmune diseases and matched for age and sex, from May 2017 to April 2018 at Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, were included. The serum of study participants were evaluated for cytomegalovirus specific immunoglobulin G (CMV-IgG), Epstein-Barr virus viral capsid antigen immunoglobulin G (EBV-VCA-IgG), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), and human immunodeficiency virus antibody (HIVAb) using commercially available the enzyme-linked immunosorbent assay (ELISA) kit.
Results: CMV-IgG was diagnosed in serum of all patients with scleroderma, while 49 (98%) healthy subjects had positive results for this test. In addition, EBV-VCA-IgG was diagnosed in 58 (89.2%) sclerodermic patients and 40 (80%) healthy subjects. The prevalence of CMV-IgG and EBV-VCA-IgG was not significantly different between patients and healthy subjects and had no significant relationship with age and sex. However, the titer of antibodies against CMV and EBV infections in the scleroderma group was higher than that in the control group (P<0.0001, and P<0.0001), respectively. The presence of HBsAg and HIVAb was not confirmed in any of the patients with scleroderma, but HCVAb was detected only in one patient. All of the individuals in control group were serologically negative for HBsAg, HCVAb, and HIVAb.
Conclusion: Serological prevalence of HBV, HCV, HIV, EBV, and CMV infections in patients with scleroderma is similar to the healthy group.

Background: Intrauterine infections (TORCH) lead to the involvement of various organs of the body of the fetus, including the eye. The aim of this study was to determine the frequency and clinical response of eye lesions to specific drugs, in infants with confirmed TORCH induced ocular lesions.
Methods: This historical cohort study from 2011 to 2017, had done in Pediatrics and Ophthalmology Department of Rasoul Akram Hospital, Tehran, Iran. Cases included; 78 infants with confirmed intrauterine infection (TORCH) with ophthalmologic disorders (glaucoma, cataract, and retinitis), 3 cases died (without any treatment). The cases with incomplete diagnosis, no treatment or without follow-up excluded from study. Out of 74 children with confirmed TORCH induced ophthalmologic disorders, finally 37 children (25 cytomegalovirus, 12 toxoplasma) were treated with specific drugs, and clinical response to treatment was followed-up to 1 year by ophthalmologic examination.
Results: From 12 cases with ophthalmologic disorders due to congenital toxoplasmosis, 5 cases had full treatment, 4 cases had complete response. One case had not any improvement. From 25 cases with congenital cytomegalovirus (CMV), 18 patients continued treatment, 9 cases with complete clinical response, 9 cases had not response to antiviral treatment, indeed most non responder cases had central nervous system involvement from birth. The best response observed in CMV infected cases accompanied with sensory hearing loss (without CNS involvement).
Conclusion: Good clinical response of ophthalmic diseases in 80% of congenital toxoplasma; and 50% of congenital cytomegalovirus infected cases. Probably with initial diagnosis and rapid treatment of cases with TORCH induced ophthalmic disorders (especially cases without CNS involvement) it would lead to stopping ocular lesions.

Background: Potency evaluation of rabies vaccine is a cheap, fast, high precision and consistent with ethical values is critical, so researchers have modified a variety of methods such as: National Institute of Health (NIH) method, Single Radial Immunodiffusion (SRID) and so on. The purpose of the present study was to replace an in vitro method consistent with medical ethics criteria instead of an in vivo method. By recognizing that the potency of the rabies vaccine depends on the amount of glycoprotein antigen content and the monoclonal antibody detect the correct folding of antigen of the rabies virus, then the glycoprotein content could be represent of vaccine potency.
Methods: In this study, we designed an immune-capture enzyme-linked immunosorbent assay (ELISA) with three antibodies (capture, primary and secondary) to determine the existent amount of viral glycoprotein in different rabies vaccines, and compared the results at the same time with measuring potency of those vaccines using the NIH method. This applied study was conducted from September 2016 to September 2018 at the Research Laboratory of the World Health Organization Collaborating Center for reference and research on rabies at the Pasteur Institute of Iran in Tehran.
Results: The slope of the standard line was calculated to R2=0.98 (P=0.0013). In the humans’ vaccines, the mean lied between 5.554-7.336 (SD=0.0463-0.1039) and the coefficient of variation was 0.778-2.436 (SD=0.0041-0.2724), at the same time in the animals’ vaccines the mean were 2.293-5.993 (SD=0.0041-0.2724) and the coefficient of variation was calculated 0.182-4.546. For animal vaccines the Pearson correlation coefficient is 0.99 and for the human vaccines this coefficient was 0.95. Also, the concordance correlation coefficient for animal vaccines was 0.98 and for human vaccines is 0.95, indicating a moderate to high concordance in both animals and humans vaccines.
Conclusion: The designed Immuno-capture ELISA kit had a proper acceptance criterion, intermediate precision, good linearity and robustness for measuring the glycoprotein level of the vaccine, which was directly related to the vaccine potency.

Primary immunodeficiency diseases (PIDs) is a diverse group of diseases, characterized by a defect in the immune system. These patients are susceptible to recurrent respiratory infections, gastrointestinal problems, autoimmune diseases, and malignancies. In most cases, patients with primary immunodeficiency disorders have genetic defects and are monogenic disorders that follow a simple Mendelian inheritance, however, some PIDs recognize a more complex polygenic origin. Overall, almost 70 to 90 percent of patients with primary immunodeficiency are undiagnosed. Given that these patients are exposing to respiratory infectious agents and some live-attenuated vaccines, thus they have a high risk to some clinical complications. The administration of oral polio vaccine in patients with PIDs especially can increase the possibility of acute flaccid paralysis. These patients will excrete the poliovirus for a long time through their feces, even though they are not paralyzed. Long-term virus proliferation in the vaccinated individuals causes a mutation in the poliovirus and creates a vaccine-derived polioviruses (VDPVs), which is a major challenge to the final stages of the worldwide eradication of polio. 
To increase the diagnosis and identification of patients with immunodeficiency and carrying out a national plan for screening patients with immunodeficiency from the fecal excretion of the poliovirus, a possible polio epidemic can be prevented during post-eradication. Development of laboratory facilities in provincial and city centers, improvement of communications among physicians regarding medical consultation and establishment of referring systems for patients by national network lead to improve status of diagnosis and treatment of patients with primary immunodefiicencies. In this context, launching and activating the national network of immunodeficiency diseases is essential for improving the health of children and reducing the cost of the health system of the country. A national network of immunodeficiency can lead to increase awareness of physicians regarding primary immunodeficiency disorders, improve collaboration among physicians about genetic consultation and establish a practical referral system in Iran that results in increased diagnosis and improve treatment of patients with primary immunodeficiency disorders.

Background: Human papillomavirus (HPV) is a large group of DNA viruses that cause skin and mucosal warts. Zinc is used in the treatment of skin diseases. Zinc has been used in the treatment of various skin and systemic diseases. Warts are benign proliferation of the skin and mucosa. The prevalence of skin warts is higher in children and its peak is in adolescence and then decreases with age. Some species of HPV can cause malignancies. The effective role of zinc in the treatment of warts has recently been discussed. This study aimed to evaluate the serum zinc levels in patients with cutaneous warts compared to healthy controls.
Methods: This case-control study was performed on patients, aged 18 to 60 years old, referred to the Dermatology Clinic of Bo’Ali Sina and Razi Hospitals, Mazandaran Province in, Iran, from April to March 2016. Serum zinc level and severity of disease were assessed in case and control groups. Data were analyzed by SPSS software, version 22 (SPSS Inc., Chicago, IL, USA).
Results: A total of 94 subjects (47 in the case and control group) entered the study. The mean age of the case group was 26.40±9.33 years and in the control group 28.32±7.35 years. The gender status was 42 (44.7%) male and 52 (56.3%) female. Single and married were 63.8% and 36.2%, respectively. The mean zinc level in patients with cutaneous wart was 82 and the control group was 85.65. The mean number of warts was 5.09±6.33. The most frequent site of lesions were on the hands and foot with 48.93% and 40.42%, respectively, and the face (3.2%) had the lowest rate. Almost half of the patients were affected by the disease for 12 to 18 months. There was no significant relationship between age, sex, and severity of disease with serum zinc level (P>0.05). Serum zinc level was significantly associated with the duration of warts involvement (P=0.043).
Conclusion: Serum zinc levels were lower in patients with cutaneous warts than in healthy controls, but this difference was not statistically significant. Serum zinc level and duration of warts involvement were related. The duration of warts and serum levels were inversely correlated.

  SARS-CoV-2 emerging from Wuhan, China is a member of the Coronaviridae family, which has so far infected and killed many people. The SARS-CoV-2 pandemic affected various aspects of life in Iran and Worldwide, and governments have imposed quarantines and travel bans on an unprecedented scale. The virus causes COVID-19, which can spread through close contact with the infected person, contaminated equipment, and suspended air droplets. The most common symptoms of the disease include fever, cough, shortness of breath, gastrointestinal symptoms, and diarrhea. In severe cases, the lung infection can occur, which causes Severe Acute Respiratory Syndrome that leads to ICU admission and even death.
  Besides, this infection can cause gastrointestinal, neurological, and renal impairments. Not merely, this new coronavirus has infected many more people worldwide in comparison to MERS and SARS, but also it has killed more people. Patients with underlying diseases such as hypertension, diabetes, respiratory problems, kidney disease, heart disease and Immunodeficiency are at higher risk of infection and potential death. Also, the risk of death and complication increases in older adults, while most of the infected children are asymptomatic. Some infected people may have mild or no symptoms but can still transmit the disease and spread it to others.
To diagnose COVID-19, serology tests, and level of ESR, CRP and other acute-phase reactants are helpful, whereas molecular tests, such as RT-PCR tests, that detect the virus’s genetic material are still the golden standard. Also, CT scan detects lung involvement; Ground-glass opacification, especially in lower lobes and subpleural region, is the most common CT characteristic, although it is not specific for COVID-19. Because the disease is difficult to diagnose, hard to prevent and challenging to treat, it has become a major concern for many countries. This review aims to gather existing information in the fields of virology, molecular pathogenesis, disease symptoms, epidemiology, clinical presentations, diagnosis, treatment, and the spread of the disease. This study also provides evidence-based prevention and treatment strategies for health policymakers, doctors, nurses, and practitioners in the field of public health, including researchers and students.

Background: Systemic lupus erythematosus is a systemic autoimmune disease that affects almost all organs of the body, and viral infections are involved in its development and progression. The present study aimed to evaluate the serological status of some viral infections in patients with systemic lupus erythematosus and a healthy population.
Methods: This descriptive study conducted from May 2017 to April 2018 at Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran on 70 patients with systemic lupus erythematosus and 70 healthy individuals who had no autoimmune diseases and were matched with the patient group for age and sex. All patients had active records and were routinely visited in rheumatology clinic of Hafez hospital, affiliated with Shiraz University of Medical Sciences. The evidence of active disease was assessed by the physicians of this practice according to the American College of Rheumatology criteria. Peripheral blood samples were collected in tubes containing EDTA and centrifuged at 3000 rpm for 5 min. The plasma of study participants was evaluated for HBsAg, HCVAb, HIVAb, EBV-VCA-IgG, and CMV-IgG using a commercially available ELISA kit.

Conclusion: Considering the higher frequency of EBV-VCA-IgG and the higher titer of antibodies against CMV and EBV in patient groups compared to healthy individuals group, it seems that periodical assessment of viral load in patients with systemic lupus erythematosus will be beneficial to prescribe medication by physicians if it is needed.

Background: The clinical field has vast sick data that has not been analyzed. Discovering a way to analyze this raw data and turn it into an information treasure can save many lives. Using data mining methods is an efficient way to analyze this large amount of raw data. It can predict the future with accurate knowledge of the past, providing new insights into disease diagnosis and prevention. Several data mining methods exist but finding a suitable one is very important. Today, coronavirus disease (COVID-19) has become one of the causing deadly diseases in the world. The early diagnosis of pandemic coronavirus disease has a significant impact in preventing death. This study aims to extract the key indications of the disease and find the best data mining methods that enhance the accuracy of coronavirus disease diagnosis.
Methods: In this study, to obtain high accuracy in diagnosing COVID-19 disease, a complete and effective workflow over data mining methods was proposed, which includes these steps: data pre-analyzing, indication selection, model creation, the measure of performance, and display of results. Data and related indications of patients with COVID-19 were collected from Kerman Afzalipour Hospital and Rafsanjan, Ali Ebn Abi Taleb Hospital. Prediction structures were made and tested via different combinations of the disease indications and seven data mining methods. To discover the best key indications, three criteria including accuracy, validation and F-value were applied and to discover the best data mining methods, accuracy and validation criteria were considered. For each data mining method, the criteria were measured independently and all results were reported for analysis. Finally, the best key indications and data mining methods that can diagnose COVID-19 disease with high accuracy were extracted.

Background: Influenza vaccines based on conserved proteins are being developed persistently. The conserved protein vaccines based on Nucleoprotein (NP) are highly protected vaccines against influenza viruses that can be used as a Universal vaccine. Aluminum hydroxide (Alum) is the most common adjuvant used in vaccine formulation to improve immunization by altering the epitopes’ folds. However, due to its toxic effects on the nervous system, especially in infants and young children exposed to multiple vaccine injections during brain development, it is better to use more desirable options such as carbohydrate-based adjuvants. Sucrose ester (SE) is a carbohydrate and non-ionic surfactant that is compatible with the human body and environmentally friendly. This study evaluated the immunogenicity of recombinant NP molecule prepared in a prokaryotic with the accompaniment of sucrose ester adjuvant against lethal influenza virus challenge in a Balb/c mice model.
Methods: The recombinant vector of PET-28a-NP was used to produce NP molecule. The vaccines containing an NP with or without Alum or sucrose ester adjuvants were injected into the mice. The Effectiveness and immunogenicity were examined by evaluating the humeral immunity induction by Immunoglobulin G (IgG), and its subunits production, and cellular immunity induction by Interferon-Gamma (IFN-γ) and Interleukin-4 (IL-4) production by ELISA Method and also animal’s surveillance was documented. The study took part at the Influenza and other respiratory viruses department of Pasteur institute of Iran in November 2018.
Results: The animals’ surveillance in the Np group was 57.1%, NP+SE was (71.4%), and NP+SE was 64.28%. Also, IgG and its subunits, IL4, and IFN-γ production in both Alum and SE combined vaccines compared to NP alone were significant.

Results: This review study showed that ozone has been successfully used to prevent several viral diseases such as COVED-19. In addition, some viruses, such as coronaviruses, contain sulfhydryl functional groups containing cysteine and tryptophan that react better with ozone gas. The infected person's sneezing may result in the formation of 40,000 droplets in the air. The droplets can be transferred to the nearest surface up to approximately 2 meters before falling and also may remain in the air for 30 hours. Conclusion: The use of ozone gas has many potential applications in inactivating viruses in enclosed spaces. Given the importance of virus-containing aerosols in the transmission of COVED-19, ozone can be a promising way to prevent the disease. The degree of inactivation of viruses by ozone gas depends on the gas concentration, contact time, temperature, humidity and type of virus. In general, studies in this field have shown the use of ozone gas in preventing the spread of viral diseases such as COVED-19. Necessary safety measures and precautions are also recommended in using this gas.

Background: The incidence of adverse perinatal outcomes including increased risk of miscarriage, preeclampsia, preterm birth and stillbirth is higher in pregnant women with coronavirus. Pregnant women who are infected with the coronavirus have placentas that are abnormal compared to the placentas of healthy women. Examples of these adverse effects have been observed before and include reduced fetal growth, pre-eclampsia, premature birth and stillbirth. Scleroderma is an uncommon connective tissue disease and its most obvious manifestation is skin fibrosis. Patients may also have involvement of visceral organs, as a result, their digestive system, kidney and heart are affected. Scleroderma also exacerbates miscarriage, fetal growth retardation, intrauterine fetal death, and preterm delivery. Pregnant women with these problems need special measures, so this study was performed to report a successful cesarean section in a woman with coronavirus and scleroderma.
Case presentation: The patient was a 31-year-old pregnant woman with a gestational age of 29 weeks who presented to Sanandaj Besat Hospital in November 2021 with symptoms of shortness of breath and dyspnea. HRCT-positive, PCR-positive, bilateral pleural effusion, and pulmonary dilatation corona were diagnosed. Due to 3 liters of vaginal bleeding and diagnosis of Décollement 60% and severe preeclampsia underwent emergency cesarean section. The live baby was born weighing 1300 g with Apgar 7. During surgery, he received 3 units of FFB and 3 units of Cryoprecipitate. Microcalcifications and fibrin thrombi were reported in the pathology of intermittent nodules. The diagnosis and treatment of this patient has significant points that are mentioned below.

Conclusion: Complications of pregnancy and childbirth in pregnant women infected with Corona virus include an increase in premature birth and an increase in the rate of cesarean section. Pregnancy in women with scleroderma at the right time and careful delivery monitoring will increase the probability of successful pregnancy outcome and all patients need counseling.

Background: Cytomegalovirus (CMV) is the most common cause of congenital infections in newborns which can lead to long-term complications in more than half of the cases with symptomatic infection at birth time. Unfortunately, neonates with congenital CMV infection will mostly remain undiagnosed because the golden time for detection is limited to the first 3 weeks of infants' life. This study aimed to determine the prevalence of congenital CMV infection in newborns admitted to intensive care units of hospitals in Tehran, Iran and assess related risk factors associated with the infection.
Methods: In this cross-sectional study from April to October 2017, newborns within the first three weeks of life who were admitted to the neonatal intensive care units (NICUs) of university-affiliated hospitals in Tehran, Iran, were eligible for enrollment. CMV infection in neonates was diagnosed through testing infants' Guthrie cards and detection of viral DNA via an in-house nested-PCR assay. Congenital CMV infection in neonates with positive results was confirmed by testing urine specimens as a sensitive and gold standard sample. Related data (demographic and maternal factors) were collected by questionnaires and analyzed.

Results: Congenital cytomegalovirus infection was diagnosed in 8 of 63 newborns (12.7%). Hearing loss was seen in 2 infected infants. The mean of head circumferences among infected neonates was significantly lower than that observed in uninfected cases. Infants with CMV related symptoms had statistically more chance to have infection (P=0.02). We also found Guthrie cards as a reliable sample with high sensitivity for CMV detection assays. Conclusion: The current study showed a high rate of symptomatic congenital CMV infection among neonates attending on NICU sections of hospitals in Tehran, Iran. It is of crucial importance to note that based on evidence, diagnosis of infants with congenital CMV infection at early stages could help to decrease the burden of long-term diseases if associated with prompt interventions and reduce the costs of late-ineffective treatment. Therefore, routine screening of newborns for congenital CMV infection via Guthrie cards is suggested.

Results: Among the 2469 surveyed people, 658 people (26.65%) were men and 1811 people (73.35%) were women. Based on ELISA test, antibody titer was reported positive in 1157 people (46.9%), including 315 men and 842 women, and 1312 people (53.1%) had negative antibody titer. The highest number of positives is related to IgG, and in IgM, the test results are mostly negative. IgM prevalence showed no gender correlation but demonstrated a significant association with patient age. Meanwhile, IgG prevalence exhibited significant relationships with both age and gender Conclusion: Considering that the city of Shiraz is considered as one of the centers of treatment in the country and a large number of patients from all parts of the country and even neighboring countries come to this city for treatment and especially for the purpose of organ transplantation; also with Considering the 46.9% prevalence of CMV infection in the region, it is recommended to use preventive methods such as vaccine and immunotherapy against CMV infection in patients

Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), hepatitis B virus (HBV), human papilloma virus (HPV), Merkel cell polyomavirus (MCPyV), human lymphotropic virus type 1 (HTLV-1) and Hepatitis C virus (HCV) are among the most important viruses that cause cancer in humans. These viruses are collectively known as oncoviruses due to their potential to induce malignant transformations in host cells. Oncoviruses exert their cancer-causing effects by utilizing various viral oncoproteins and non-coding RNAs, which can drive host cells toward malignancy through multiple pathways. One critical strategy these viruses employ involves altering the host cell's regulatory mechanisms, particularly by influencing DNA methylation processes.
DNA methylation is a crucial modification that occurs on the promoter regions of genes, effectively reducing their expression levels. Under normal cellular conditions, a delicate balance of methylation and demethylation is maintained by a specific set of enzymes. Key players in this process include DNA methyltransferases (DNMTs) and TET methylcytosine dioxygenases (TETs), which are pivotal in regulating gene expression through methylation. These enzymes are prime targets for oncoviruses because, by altering their activity, viruses can hijack the host cell's regulatory machinery. Viral oncoproteins, though diverse in structure and function, often converge on disrupting the expression of these enzymes. By doing so, they induce widespread changes in DNA methylation patterns, effectively reprogramming the gene expression landscape of the host cell. This reprogramming is not random; rather, it is a calculated mechanism through which oncoviruses can manipulate the cell cycle, promoting uncontrolled cellular proliferation and progression towards cancer. By suppressing or activating specific genes, these viruses can push cells past normal checkpoints, eventually leading to tumor formation. Despite the critical role of DNA methylation in cancer development, the precise mechanisms by which oncoviruses modulate these methylation processes are not fully understood. Researchers have made significant progress in exploring the connection between viral infections and cancer, but many of the detailed pathways through which oncoviruses control methylation remain to be elucidated. As a result, this area remains a fertile ground for further research, offering potential avenues for therapeutic intervention in virus-induced cancers.

Background: The exact cause chronic lymphocytic leukemia (CLL) is still unknown. Cytomegalovirus (CMV) may play a role in the development of CLL, Therefore, the aim of this study is to investigate the frequency of CMV in patients with CLL and its relationship with blood and genetic factors.
Methods: This cross-sectional study was conducted between April 2020 and October 2022 on 40 CLL patients that referred to Dr. Daneshbod Pathobiology Laboratory (Shiraz, Iran). After taking blood and separating the buffy coat, viral DNA was extracted using a commercial DNA extraction kit and the CMV burden was measured using Real-time PCR assay. Moreover, a blood cell count test was performed. The amount of lactate dehydrogenase of the serum was measured using the kit. Also, common chromosomal disorders and CD38 marker related data were extracted from the file patients. SPSS software and Student's t-test were used to result analysis.
Results: The mean age of the patients was 62.25 ± 10.49 years. Of the 40 patients, 28 were men (70%). The average number of white blood cells was 46.06±1.49* 10⁹, which was significantly higher in women than in men (p=0.031). Real-time PCR results showed that two patients (5%) have detectable amounts of CMV virus genome. The level of lactate dehydrogenase, CD38 marker, and the number of malignant cells in male and female patients did not differ significantly (p=0.362). Moreover, chromosomal abnormalities include deletions in 11q (ATM) and 17P (TP53), were observed in 3 (7.5%) and 4 (10%) patients, respectively.
Conclusion: Our finding indicated the CMV might not involve in the pathogenesis of CLL disease. More studies are recommended for clarify this finding.