Knowledge of cytomegalovirus and available prevention strategies in pregnancy: a cross-sectional study in Portugal.

OBJECTIVE: Maternal and fetal congenital infection by cytomegalovirus (CMV) during pregnancy is the leading infectious cause of neurologic impairment and hearing loss. Efforts at limiting CMV exposure are based on hygienic measures. This study assessed the relationship between CMV knowledge and pregnant women's time perspective as per the Zimbardo Time Perspective Inventory (ZTPI) scale. METHODS: We conducted a prospective descriptive study at a secondary-care Portuguese hospital between October to November 2021. All consecutive pregnant women in antenatal third-trimester appointments were included. The questionnaire included: sociodemographic data, knowledge about CMV, and the ZTPI scale, validated to our population. The number of correct answers in the knowledge section of the questionnaire was tallied to determine the individual knowledge score (KS). We investigated patients subjective perceptions of CMV infection during pregnancy, CMV knowledge, and CMV serologic status of pregnant women. RESULTS: We enrolled 96 pregnant women. 81.0% had not previously heard about CMV and only 8.8% had heard about it through their obstetrician. No significant association between awareness of CMV and education level was detected. 16.0% of pregnant women declared that they were aware of the hygienic measures for CMV. The CMV serology was performed in 21.3% of those enrolled in the preconception assessment, and 13.8% proved to be immune. From the time perspective, half of the women displayed a future-oriented attitude. Future-oriented women had significantly higher KS. No significant association was found between KS and education level, age, or previous pregnancy. There was a significant association between KS and women that work in health care. CONCLUSIONS: Most patients had no knowledge of CMV. Being a medical professional and having a future-oriented outlook increases knowledge about CMV. Primary health care and obstetrics doctors may play a crucial role in informing pregnant women of antenatal appointments. The CMV serology coverage is scarce in this sample. This study constitutes a first step toward raising the awareness of the general population about CMV.

Therapeutic targeting of HCMV-encoded chemokine receptor US28: Progress and challenges.

The pervasive human cytomegalovirus (HCMV) causes significant morbidity in immunocompromised individuals. Treatment using the current standard-of-care (SOC) is limited by severe toxic adverse effects and anti-viral resistance development. Furthermore, they only affect HCMV in its lytic phase, meaning viral disease is not preventable as latent infection cannot be treated and the viral reservoirs persist. The viral chemokine receptor (vCKR) US28 encoded by HCMV has received much attention in recent years. This broad-spectrum receptor has proven to be a desirable target for development of novel therapeutics through exploitation of its ability to internalize and its role in maintaining latency. Importantly, it is expressed on the surface of infected cells during both lytic and latent infection. US28-targeting small molecules, single-domain antibodies, and fusion toxin proteins have been developed for different treatment strategies, e.g. forcing reactivation of latent virus or using internalization of US28 as a toxin shuttle to kill infected cells. These strategies show promise for providing ways to eliminate latent viral reservoirs and prevent HCMV disease in vulnerable patients. Here, we discuss the progress and challenges of targeting US28 to treat HCMV infection and its associated diseases.

Primary immunodeficiency screening in an infant with cytomegalovirus disease reveals HIV infection.

Cytomegalovirus is widely spread worldwide, and it is not uncommon for it to complicate the congenital human immunodeficiency virus (HIV) disease as an acquired or congenital coinfection. However, the association of the two infections is not common amongst infants with primary immune deficiencies.We describe a case of a 6-month-old infant with acquired cytomegalovirus and HIV infections, diagnosed in the course of the patient's clinical and laboratory workup for a presumed primary immunodeficiency. To date, this is the first reported case of such a combination in a child from Bulgaria.

Enfermedad por citomegalovirus en los pacientes inmunodeprimidos por glomerulonefritis necrosante pauciinmune / Cytomegalovirus disease in immunosuppressed patients with necrotizing pauci-immune glomerulonephritis

Introducción: La afectación renal por glomerulonefritis necrosante pauciinmune (GNPI) asociada a vasculitis de pequeño vaso requiere tratamiento inmunodepresor, cuyos efectos secundarios incluyen un mayor riesgo de procesos infecciosos, como la enfermedad por citomegalovirus (CMV), aunque no hay recomendaciones sobre su manejo en las guías de práctica clínica (GPC).ObjetivoEstudiar la incidencia de enfermedad por CMV y sus determinantes.Pacientes y métodosPacientes con diagnóstico histológico de GNPI en los últimos 10 años, determinando la carga viral de CMV y analizando los determinantes de su concurrencia.ResultadosSe realizaron 44 biopsias durante el periodo de estudio. Del total, 11 pacientes (25%) desarrollaron enfermedad por CMV; todos habían recibido tratamiento inmunodepresor. Cuatro (30,8%) fallecieron durante el ingreso. Los factores determinantes de la enfermedad fueron la edad (por cada 10 años OR: 3,0, IC 95%: 1,0 a 8,9, p = 0,012) y la albúmina (por cada g/L OR: 0,8, IC 95%: 0,6 a 1,0, p = 0,012).ConclusionesLa incidencia de enfermedad por CMV en pacientes inmunodeprimidos por GNPI es alta, con alta mortalidad. Sería necesario incluir estrategias en las GPC para prevenir su desarrollo. (AU)

Introduction: Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG).ObjectiveTo study the incidence of CMV disease and its determinants.Patients and methodsPatients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence.ResultsForty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012).ConclusionsThe incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it. (AU)

A co-infection of Pneumocystis jirovecii and Lophomonas blattarum causing pneumonia in a patient with adenocarcinoma of lung.

Patients with lung cancer suffer frequent infections which not only thwart the effect of oncological treatment but also affect overall survival. We present a fatal case where coinfection of Pneumocystis jirovecii and Lophomonas blattarum caused pneumonia in a patient with advanced and treated metastatic adenocarcinoma of lung. Cytomegalovirus (CMV) PCR was positive for the patient. Newer pathogens are not only emerging but also there is an increase in incidence of coinfections. Pneumonia due to coinfection of Pneumocystis jirovecii and Lophomonas blattarum is rare and unusual and requires high degree of suspicion and skill for the diagnosis.

Cytomegalovirus reactivation in a SARS-CoV-2 infected woman experiencing fetal demise in the first trimester with fetal trisomy 21: A case report.

Cytomegalovirus (CMV) is the most common cause of congenital viral infections. Women seropositive for CMV prior to pregnancy can develop a non-primary CMV infection. Here, we present a case of first trimester pregnancy loss during active SARS-CoV-2 infection. There was no evidence of SARS-CoV-2 RNA in placenta and fetal tissue, but there was presence of congenital cytomegalovirus infection by nested PCR. To the best of our knowledge, this is the first report demonstrating association of early congenital CMV infection due to reactivation and fetal demise in a SARS-CoV-2 positive woman with fetal trisomy 21.

Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes.

In sequential sera from pregnant women with HCMV primary infection (PI), the serum neutralizing activity is higher against virions produced in epithelial and endothelial cells than in fibroblasts. Immunoblotting shows that the pentamer complex/trimer complex (PC/TC) ratio varies according to the producer cell culture type used for the virus preparation to be employed in the neutralizing antibody (NAb) assay, and is lower in fibroblasts and higher in epithelial, and especially endothelial cells. The blocking activity of TC- and PC-specific inhibitors varies according to the PC/TC ratio of virus preparations. The rapid reversion of the virus phenotype following its back passage to the original cell culture (fibroblasts) potentially argues in favor of a producer cell effect on virus phenotype. However, the role of genetic factors cannot be overlooked. In addition to the producer cell type, the PC/TC ratio may differ in single HCMV strains. In conclusion, the NAb activity not only varies with different HCMV strains, but is a dynamic parameter changing according to virus strain, type of target and producer cells, and number of cell culture passages. These findings may have some important implications for the development of both therapeutic antibodies and subunit vaccines.

CD4+ T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV.

Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1+, GPR56+, and CD57+/- T cells (termed CGC+) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC+CD4+ T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC+CD4+ T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC+CD4+ T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4+ T cell subsets, suggesting a potentially greater capacity for fatty acid ß-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC+. Together, this study suggests that among PWH, CGC+ CD4+ T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals.

Dynamic kernel matching for non-conforming data: A case study of T cell receptor datasets.

Most statistical classifiers are designed to find patterns in data where numbers fit into rows and columns, like in a spreadsheet, but many kinds of data do not conform to this structure. To uncover patterns in non-conforming data, we describe an approach for modifying established statistical classifiers to handle non-conforming data, which we call dynamic kernel matching (DKM). As examples of non-conforming data, we consider (i) a dataset of T-cell receptor (TCR) sequences labelled by disease antigen and (ii) a dataset of sequenced TCR repertoires labelled by patient cytomegalovirus (CMV) serostatus, anticipating that both datasets contain signatures for diagnosing disease. We successfully fit statistical classifiers augmented with DKM to both datasets and report the performance on holdout data using standard metrics and metrics allowing for indeterminant diagnoses. Finally, we identify the patterns used by our statistical classifiers to generate predictions and show that these patterns agree with observations from experimental studies.

Control of human cytomegalovirus replication by liver resident natural killer cells.

Natural killer cells are considered to be important for control of human cytomegalovirus- a major pathogen in immune suppressed transplant patients. Viral infection promotes the development of an adaptive phenotype in circulating natural killer cells that changes their anti-viral function. In contrast, less is understood how natural killer cells that reside in tissue respond to viral infection. Here we show natural killer cells resident in the liver have an altered phenotype in cytomegalovirus infected individuals and display increased anti-viral activity against multiple viruses in vitro and identify and characterise a subset of natural killer cells responsible for control. Crucially, livers containing natural killer cells with better capacity to control cytomegalovirus replication in vitro are less likely to experience viraemia post-transplant. Taken together, these data suggest that virally induced expansion of tissue resident natural killer cells in the donor organ can reduce the chance of viraemia post-transplant.

Overview and update on cytomegalovirus-associated anterior uveitis and glaucoma.

Cytomegalovirus anterior uveitis is the most common ocular inflammatory disease caused by cytomegalovirus infection. It mainly occurs in middle-aged males with competent immunologic function, and the incidence is higher in Asia. The clinical manifestations vary from Posner-Schlossman syndrome and corneal endotheliitis to Fuchs uveitis syndrome, and are often accompanied by intraocular hypertension. Secondary glaucoma is a potentially blinding ocular complication with a pathogenesis that includes complicated immunological factors, intraocular inflammation, different types of angle abnormalities, and the administration of steroids, which may result in physical discomfort and visual impairment. Diagnostic tests, such as the polymerase chain reaction, optical coherence tomography, ocular microscopy, and confocal microscopy, might help in identifying anterior uveitis caused by other viruses. Combinations of antiviral medications and anti-inflammatory agents are effective treatments. If pharmacological therapy cannot reduce intraocular pressure or slow the progression of glaucomatous optic neuropathy, surgical intervention is required as a last resort.

Severe CMV pneumonitis and the resulting ARDS in a 28-year-old pregnant woman: a case report.

BACKGROUND: Cytomegalovirus (CMV) is a common virus. In pregnant women, CMV infection is usually mildly symptomatic or asymptomatic but can lead to fetal infection. Here we present a rare case of severe CMV pneumonitis and acute respiratory distress syndrome in a healthy immunocompetent pregnant woman. CASE PRESENTATION: A previous healthy 28-year-old woman with spontaneous conception, was admitted to the General University Hospital of Patras at 29 weeks of gestation with a day history of fever, fatigue, pharyngitis, and cough. She was diagnosed with acute CMV infection and CMV pneumonitis. During her hospitalization she developed acute distress syndrome (ARDS). The patient was intubated and underwent emergency caesarean delivery. She was admitted to the intensive care unit and received intravenous ganciclovir. She was discharged at 20th day postpartum in a good clinical condition. CONCLUSIONS: This case highlights the infrequent yet potential complexity of CMV infection in immunocompetent patients and in pregnancy.

[Effect of breastfeeding on immune function in infants with human cytomegalovirus infection]. / æ¯ä¹³å–‚å »å¯¹äººå·¨ç»†èƒžç— æ¯’æ„ŸæŸ“å©´å„¿å ç–«åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To study the effect of breastfeeding on immune function in infants with human cytomegalovirus (HCMV) infection. METHODS: A retrospective analysis was performed on the medical data of 135 infants with HCMV infection who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2021 to May 2022, and all these infants received breastfeeding. According to the results of breast milk HCMV-DNA testing, the infants were divided into two groups: breast milk HCMV positive (n=78) and breast milk HCMV negative (n=57). According to the median breast milk HCMV-DNA load, the infants in the breast milk HCMV positive group were further divided into two subgroups: high viral load and low viral load (n=39 each). Related indicators were compared between the breast milk positive and negative HCMV groups and between the breast milk high viral load and low viral load subgroups, including the percentages of peripheral blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells), CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load. RESULTS: There were no significant differences in the percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load between the breast milk HCMV positive and HCMV negative groups, as well as between the breast milk high viral load and low viral load subgroups (P>0.05). CONCLUSIONS: Breastfeeding with HCMV does not affect the immune function of infants with HCMV infection.

Tomographic, microbiological and histological characterization of secondary apical periodontitis: case series.

This case series included a tomographic, microbiological, and histopathological description of 15 secondary apical periodontitis (SAP) lesions obtained by apical microsurgery performed in 10 patients to better understand the etiology and pathogenesis of SAP. Preoperative tomographic analyses were performed through Cone beam computerized tomography - Periapical index (CBCT-PAI), and apical microsurgeries were then carried out. The removed apices were used for microbial culturing and for molecular identification using PCR for the detection of 5 strict anaerobic bacteria (P. gingivalis, P. intermedia, P. nigrescens, T. forsythia, and T.denticola) and 3 viruses Herpes simplex viruses (HSV), Cytomegalovirus (CMG) and Epstein-Barr Virus (EBV) by nested PCR. The removed apical lesions were histologically described. Univariate statistical analyses were performed by using STATA MP/16 (StataCorp LLC, College Station, TX, United States). CBCT-PAI analyses revealed PAI 4 and PAI 5 score lesions that involved cortical plate destruction. Eight SAPs were positive by culture, while nine SAP lesions were positive by PCR. Fusobacterium species were the most frequently cultured organisms in 7 SAP lesions, followed by D. pneumosintes in 3. In contrast, by single PCR, T. forsythia and P. nigrescens were detected in 5 lesions, T. denticola in 4 lesions, and P. gingivalis in 2 lesions. Twelve periapical lesions were granulomas, and the remaining three SAP lesions were radicular cysts. In conclusion, this case series study revealed that secondary apical lesions presented tomographic involvement of PAI 3 to 5, and that most SAP lesions were apical granulomas containing anaerobic and facultative microorganisms.

Seroprevalence of Toxoplasma, Rubella and Cytomegalovirus in Women of Fertility Age in Our Region

Objective: Toxoplasma gondii (T. gondii), Rubella and Cytomegalovirus (CMV) infections can cause severe morbidity in the fetus when transmissed during pregnancy. In our study, it was aimed to examine the seropositivity rates for T. gondii, Rubella and CMV infections in women of childbearing age who applied to our hospital. Methods: Anti-Toxoplasma IgG, anti-Toxoplasma IgM, anti-Rubella IgG, anti-Rubella IgM, anti-CMV IgG and anti-CMV were studied in women of childbearing age (18-49 years old) who applied to our hospital's outpatient clinics between January 2018 and December 2020. The tests were performed in our microbiology laboratory using the ELISA method on Architect i2000 (Abbott, USA) and COBAS e601 (Roche, Germany) devices. Results: As a result of the data obtained, the percentages of IgM and IgG positivity for anti-Toxoplasma were calculated as 1.4% and 30.9%, respectively. Anti-Rubella IgM positivity was 0.7%, anti-Rubella IgG positivity was 91%, anti-CMV IgG positivity was 98.8%, and anti-CMV IgM positivity was 2%. Conclusion: Having its own seroprevalence for each region has is important in terms of planning pregnancy screenings. The seropositivity rates in our region are in line with other studies in the country. Since CMV seropositivity is very high in the population and there is no effective treatment or vaccine, screening may not be not necessary. T. gondii and Rubella screenings can be recommended due to the lower immunity rates and the availability of vaccine and treatment options.

Prospective Evaluation of CD45RA+/CCR7- Effector Memory T (TEMRA) Cell Subsets in Patients with Primary and Secondary Brain Tumors during Radiotherapy of the Brain within the Scope of the Prospective Glio-CMV-01 Clinical Trial.

Radiotherapy (RT) of the brain is a common treatment for patients with high-grade gliomas and brain metastases. It has previously been shown that reactivation of cytomegalovirus (CMV) frequently occurs during RT of the brain. This causes neurological decline, demands antiviral treatment, and is associated with a worse prognosis. CMV-specific T cells are characterized by a differentiated effector memory phenotype and CD45RA+ CCR7- effector memory T (TEMRA) cells were shown to be enriched in CMV seropositive individuals. In this study, we investigated the distribution of TEMRA cells and their subsets in the peripheral blood of healthy donors and, for the first time, prospectively within the scope of the prospective Glio-CMV-01 clinical trial of patients with high-grade glioma and brain metastases during radiation therapy as a potential predictive marker. First, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of TEMRA cells in a longitudinal manner. The CMV serostatus and age were considered as influencing factors. We revealed that patients who had a reactivation of CMV have significantly higher amounts of CD8+ TEMRA cells. Further, the distribution of the subsets of TEMRA cells based on the expression of CD27, CD28, and CD57 is highly dependent on the CMV serostatus. We conclude that the percentage of CD8+ TEMRA cells out of all CD8+ T cells has the potential to serve as a biomarker for predicting the risk of CMV reactivation during RT of the brain. Furthermore, this study highlights the importance of taking the CMV serostatus into account when analyzing TEMRA cells and their subsets.

Human cytomegalovirus infection perturbs neural progenitor cell fate via the expression of viral microRNAs.

Human cytomegalovirus (HCMV) preferentially targets neural progenitor cells (NPCs) in congenitally infected fetal brains, inducing neurodevelopmental disorders. While HCMV expresses several microRNAs (miRNAs) during infection, their roles in NPC infection are unclear. Here, we characterized expression of cellular and viral miRNAs in HCMV-infected NPCs during early infection by microarray and identified seven differentially expressed cellular miRNAs and six significantly upregulated HCMV miRNAs. Deep learning approaches were used to identify potential targets of significantly upregulated HCMV miRNAs against differentially expressed cellular messenger RNA (mRNAs), and the associations with miRNA-mRNA expression changes were observed. Gene ontology enrichment analysis indicated cellular gene targets were significantly enriched in pathways involved in neurodevelopment and cell-cycle processes. Viral modulation of selected miRNAs and cellular gene targets involved in neurodevelopmental processes were further validated by real-time quantitative reverse transcription polymerase chain reaction. Finally, a predicted 3' untranslated region target site of hcmv-miR-US25-1 in Jag1, a factor important for neurogenesis, was confirmed by mutagenesis. Reduction of Jag1 RNA and protein levels in NPCs was observed in response to transient expression of hcmv-miR-US25-1. A hcmv-miR-US25-1 mutant virus (ΔmiR-US25) displayed limited ability to downregulate Jag1 mRNA levels and protein levels during the early infection stage compared with the wild type virus. Our collective experimental and computational investigation of miRNAs and cellular mRNAs expression in HCMV-infected NPCs yields new insights into the roles of viral miRNAs in regulating NPC fate and their contributions to HCMV neuropathogenesis.

Cytomegalovirus viral load as predictor of the clinical course of hypoxic pneumonia in children.

BACKGROUND: Children under 1 year of age with hypoxic pneumonia regularly have concurrent cytomegalovirus (CMV) viremia. In these children, the diagnosis of CMV-associated pneumonia and the prediction of an outcome are difficult. It is unclear whether quantification of blood CMV viral load (CMV-VL) can predict outcomes in these children.METHODS: This was a retrospective study including children (1-12 months of age), with detectable CMV-VL and hypoxic pneumonia admitted to the paediatric intensive care unit of Tygerberg Hospital, Cape Town, South Africa between 1 January 2014 and 31 December 2015. Clinical, radiological and biochemical data were collected.RESULTS: Of the 87 participants included (median age: 3.9 months, IQR 2.2-4.8), 35 were (40%) born prematurely. The median weight-for-age Z-score was -2.68 (IQR -3.0 to -0.83); 37 (43%) were severely underweight for age; 27 (31%) were HIV-positive, 3 were on ART. The median CMV-VL was log 4.0 (IQR 3.3-4.79); CMVhigh was defined as CMV-VL > median; CMV-VL < median was classified as CMVlow. Overall survival was 90%; 12 (15.4%) remained oxygen-dependent at Day 28 post-admission. There was no difference in survival, 24-h post-admission ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2:FiO2), oxygen dependence or ventilation duration between CMVlow and CMVhigh. High-frequency oscillation ventilation duration was longer (P = 0.005) and Pneumocystis jirovecii (PJP) co-infection more frequent (P = 0.018) in CMVhigh.CONCLUSION: CMV-VL is unable to predict the clinical outcome in children with hypoxic pneumonia. Specific treatment for CMV should be considered in all children at risk of CMV-associated pneumonia with detectable CMV-VL.

CRM197-conjugated peptides vaccine of HCMV pp65 and gH induce maturation of DC and effective viral-specific T cell responses.

Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

PARP in the neuropathogenesis of cytomegalovirus infection - Possible role and therapeutic perspective.

Cytomegalovirus infects the majority of the population globally. Congenital CMV infection acquired through primary maternal infection in pregnancy is the most common intrauterine infection with a high mortality rate due to severe long-term neurodevelopmental sequelae. The demyelination and neuroinflammation during CMV infection have been attributed to altered immune response and ROS-mediated apoptosis. PARP-1 protein is linked to apoptotic neuronal loss with subsequent neurotoxicity and CNS injury as a result of PARP hyperactivation. PARP-1 play a critical role in the establishment of latency including EBV, HHV-8 and HIV. Research on PARP inhibitors recently shows significant progress against neurodegenerative diseases such as Alzheimer's disease and cancer therapy including malignant lymphoma and hepatitis B virus-induced hepatocellular carcinoma. The role of PARP1 in the neuropathogenesis of CMV and the potential of PARP inhibitors in the prevention of neurological sequelae is still elusive. Further studies on the role of PARP on the neuropathogenesis of CMV infection can help thwart neurodegeneration through the potential development of PARP inhibitors such as small molecule inhibitors.