ABSTRACT
PURPOSE: Evaluate cytomegalovirus (CMV) post-prophylaxis surveillance in high-risk (D+/R-) kidney and liver transplant recipients. METHODS: Adult D+/R- patients were included if transplanted between 6/1/15 and 11/30/22 and divided into a pre-CMV-stewardship-era (6/1/15-5/31/18), CMV-stewardship-era (6/1/18-6/30/20), and a surveillance-era (7/1/2020-11/30/2022) then followed through 12 months. The primary objective was to evaluate CMV-related outcomes. The secondary objective was to assess graft and patient survival by era. RESULTS: There were 328 patients in the study period; 133 in the pre-stewardship-era, 103 in the stewardship-era, and 92 in the surveillance-era. Replication rates in the surveillance-era were significantly higher, as anticipated due to increased sampling (pre 38.4%, stewardship 33.0%, surveillance 52.2%, p = 0.02). Time from transplant to first replication was similar (pre 214.0 ± 79.0 days, stewardship 231.1 ± 65.5, surveillance 234.9 ± 61.4, p = 0.29). CMV viral load (VL) at first detection, maximum-VL, and incidence of VL > 100 000 IU/mL were numerically lower in the surveillance era, although not statistically significant. CMV end-organ disease (p < 0.0001) and ganciclovir-resistance (p = 0.002) were significantly lower in the surveillance era than in both previous eras. Rejection was not different between eras (p = 0.4). Graft (p = 0.0007) and patient survival (p = 0.008) were significantly improved in the surveillance era. CONCLUSIONS: Post-prophylaxis surveillance significantly reduced CMV end-organ disease and resistance. Despite observing increased replication rates in the surveillance era, rejection was not significantly different and there was no graft loss or patient mortality at 12 months.
Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Cytomegalovirus , Drug Resistance, Viral , Ganciclovir , Graft Rejection , Graft Survival , Kidney Transplantation , Liver Transplantation , Humans , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/epidemiology , Male , Female , Middle Aged , Cytomegalovirus/isolation & purification , Cytomegalovirus/drug effects , Antiviral Agents/therapeutic use , Ganciclovir/therapeutic use , Follow-Up Studies , Liver Transplantation/adverse effects , Risk Factors , Kidney Transplantation/adverse effects , Prognosis , Graft Rejection/prevention & control , Graft Rejection/etiology , Graft Rejection/virology , Postoperative Complications/prevention & control , Adult , Survival Rate , Retrospective Studies , Transplant Recipients/statistics & numerical dataABSTRACT
Cytomegalovirus (CMV) infection poses risks to newborns, necessitating effective therapies. Given that the damage includes both viral infection of brain cells and immune system-related damage, here we investigate the involvement of cellular prion protein (PrP), which plays vital roles in neuroprotection and immune regulation. Using a murine model, we show the role of PrP in tempering neonatal T cell immunity during CMV infection. PrP-null mice exhibit enhanced viral control through elevated virus-specific CD8 T cell responses, leading to reduced viral titers and pathology. We further unravel the molecular mechanisms by showing CMV-induced upregulation followed by release of PrP via the metalloproteinase ADAM10, impairing CD8 T cell response specifically in neonates. Additionally, we confirm PrP downregulation in human CMV (HCMV)-infected fibroblasts, underscoring the broader relevance of our observations beyond the murine model. Furthermore, our study highlights how PrP, under the stress of viral pathogenesis, reveals its impact on neonatal immune modulation.
Subject(s)
Animals, Newborn , CD8-Positive T-Lymphocytes , Cytomegalovirus Infections , Cytomegalovirus , Mice, Knockout , Animals , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Cytomegalovirus/immunology , Humans , Mice , CD8-Positive T-Lymphocytes/immunology , Female , Fibroblasts/metabolism , Fibroblasts/virology , Prion Proteins/metabolism , Prion Proteins/genetics , Mice, Inbred C57BL , Disease Models, Animal , ADAM10 Protein/metabolism , ADAM10 Protein/geneticsABSTRACT
OBJECTIVE: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations. METHODS: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years. RESULTS: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes. CONCLUSION: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late.
Subject(s)
Cytomegalovirus Infections , Humans , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnosis , Female , Male , Child , Child, Preschool , Infant , Adolescent , Longitudinal Studies , Microcephaly/virology , Microcephaly/etiology , Cerebral Palsy , Hearing Loss/virology , Hearing Loss/etiology , Hearing Loss/diagnosis , Intellectual Disability/virology , Fetal Growth Retardation/virology , Vision Disorders/virology , Vision Disorders/etiology , Vision Disorders/diagnosis , Infant, Newborn , Prognosis , Cytomegalovirus/pathogenicity , Follow-Up StudiesABSTRACT
PURPOSE: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R-) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. METHODS: A review of patient records from January 2010 to December 2020 with follow-up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. RESULTS: Two hundred and twenty-one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty-six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). CONCLUSIONS: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation.
Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Cytomegalovirus , Graft Survival , Heart Transplantation , Humans , Heart Transplantation/adverse effects , Heart Transplantation/mortality , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/epidemiology , Female , Male , Cytomegalovirus/isolation & purification , Follow-Up Studies , Adult , Prognosis , Retrospective Studies , Antiviral Agents/therapeutic use , Risk Factors , Graft Rejection/prevention & control , Graft Rejection/etiology , Graft Rejection/mortality , Survival Rate , Middle Aged , Postoperative Complications/prevention & control , Tissue Donors/supply & distributionABSTRACT
Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses.
Subject(s)
Cytomegalovirus , Viral Envelope Proteins , Viral Envelope Proteins/immunology , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/metabolism , Cytomegalovirus/immunology , Humans , Animals , Mice , Cryoelectron Microscopy , Protein Conformation , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Virus Internalization , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Protein Stability , Cytomegalovirus Vaccines/immunology , Amino Acid Substitution , Models, MolecularSubject(s)
Cytomegalovirus Infections , Cytomegalovirus , Fetus , Humans , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/pathology , Female , Pregnancy , Cytomegalovirus/genetics , Fetus/virology , Fetus/pathology , Fetus/diagnostic imaging , Amniotic Fluid/virology , Magnetic Resonance Imaging , Retrospective Studies , Ultrasonography, Prenatal , Fetal Growth Retardation/virology , Fetal Diseases/virology , Fetal Diseases/pathology , Pregnancy Complications, Infectious/virology , Pregnancy Complications, Infectious/pathology , AutopsyABSTRACT
Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates L1 expression by enhancing both the expression of L1-activating transcription factors, YY1 and RUNX3, and the chromatin accessibility of L1 promoter regions. Increased L1 expression, in turn, promotes HCMV replicative fitness. Affinity proteomics reveals UL44, HCMV DNA polymerase subunit, as the most abundant viral binding protein of the L1 ribonucleoprotein (RNP) complex. UL44 directly interacts with L1 ORF2p, inducing DNA damage responses in replicating HCMV compartments. While increased L1-induced mutagenesis is not observed in HCMV for genetic adaptation, the interplay between UL44 and ORF2p accelerates viral DNA replication by alleviating replication stress. Our findings shed light on how HCMV exploits host retrotransposons for enhanced viral fitness.
Subject(s)
Cytomegalovirus , DNA Replication , Long Interspersed Nucleotide Elements , Viral Proteins , Virus Replication , Humans , Cytomegalovirus/genetics , Cytomegalovirus/physiology , Virus Replication/genetics , Viral Proteins/metabolism , Viral Proteins/genetics , DNA Replication/genetics , Long Interspersed Nucleotide Elements/genetics , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/genetics , Host-Pathogen Interactions/genetics , Retroelements/genetics , DNA-Binding ProteinsABSTRACT
Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/µl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Milk, Human , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Sensitivity and Specificity , Humans , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Milk, Human/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Nucleic Acid Amplification Techniques/methods , Molecular Diagnostic Techniques/methods , Female , Infant, Newborn , Time FactorsABSTRACT
Cytomegalovirus (CMV) infection is the main opportunistic infection observed after kidney transplantation. Despite the use of prevention strategies, CMV disease still occurs, especially in high-risk patients (donor seropositive/recipient seronegative). Patients may develop complicated CMV, i.e. recurrent, refractory or resistant CMV infection. CMV prevention relies on either universal prophylaxis or preemptive therapy. In high-risk patients, universal prophylaxis is usually preferred. Currently, valganciclovir is used in this setting. However, valganciclovir can be responsible for severe leucopenia and neutropenia. A novel anti-viral drug, letermovir, has been recently compared to valganciclovir. It was as efficient as valganciclovir to prevent CMV disease and induced less hematological side-effects. It is still not available in France in this indication. Recent studies suggest that immune monitoring by ELISPOT or Quantiferon can be useful to determine the duration of prophylaxis. Other studies suggest that prophylaxis may be skipped in CMV-seropositive kidney-transplant patients given mTOR inhibitors. Refractory CMV is defined by the lack of decrease of CMV DNAemia of at least 1 log10 at 2 weeks after effective treatment. In case of refractory CMV infection, drug resistant mutations should be looked for. Currently, maribavir is the gold standard therapy for refractory/resistant CMV. At 8 weeks therapy and 8 weeks later, it has been shown to be significantly more effective than other anti-viral drugs, i.e. high dose of ganciclovir, foscarnet or cidofovir. However, a high rate of relapse was observed after ceasing therapy. Hence, other therapeutic strategies should be evaluated in order to improve the sustained virological rate.
L'infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Malgré les stratégies préventives, il persiste des maladies à CMV, notamment chez les patients à haut risque (donneur séropositif/receveur séronégatif). Certains patients présentent des formes complexes avec des récurrences et des infections réfractaires et/ou résistantes aux antiviraux. La prévention de l'infection à CMV repose soit sur une prophylaxie universelle, soit sur une stratégie préemptive. Chez les patients à haut risque, la stratégie prophylactique est le plus souvent utilisée. Elle repose sur l'utilisation du valganciclovir, qui peut être responsable de leucopénies et de neutropénies sévères. Un nouvel antiviral, le létermovir, qui n'est pas encore disponible sur le marché en France dans cette indication, a montré une efficacité similaire au valganciclovir avec peu d'effets secondaires hématologiques. Des études récentes suggèrent l'intérêt de l'immuno-surveillance par ELISPOT ou Quantiféron pour guider la durée de la prophylaxie. D'autres études suggèrent également la possibilité de se passer d'un traitement prophylactique anti-CMV chez des transplantés rénaux CMV-séropositifs recevant des inhibiteurs de la mTOR. Le CMV réfractaire est défini par une absence de baisse de la charge virale d'au moins 1 log10 après deux semaines de traitement efficace. En cas d'absence de baisse de la charge virale, une recherche de mutations de résistance aux antiviraux doit être effectuée. Actuellement, le maribavir constitue le traitement de référence pour les formes réfractaires et résistantes. La clairance virale à la fin du traitement, ou huit semaines plus tard, est significativement supérieure à celle observée avec les autres antiviraux tels que le ganciclovir donné à forte dose, le foscarnet, ou le cidofovir. Cependant, le taux de rechute à l'arrêt du traitement par maribavir reste important. D'autres stratégies thérapeutiques doivent être évaluées pour améliorer ce taux de réponse virologique soutenue.
Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/prevention & control , Antiviral Agents/therapeutic use , Valganciclovir/therapeutic use , Quinazolines/therapeutic use , Ganciclovir/therapeutic use , Ribonucleosides/therapeutic use , Acetates , Dichlororibofuranosylbenzimidazole/analogs & derivativesABSTRACT
Previous studies of the immune control of cytomegalovirus infection have primarily focused on analysis of the traditional adaptive T-cell response. Donadeu et al. bring a new perspective through evaluation of multiple adaptive and innate immune subtypes in parallel with cytomegalovirus-specific cell-mediated immunity in a prospective cohort of kidney transplant recipients with findings validated in 2 independent studies. Identification of a natural killer T-cell subtype associated with cell-mediated immunity and freedom from cytomegalovirus infection demonstrates the importance of the coordinated innate and adaptive immune response for effective viral control.
Subject(s)
Adaptive Immunity , Cytomegalovirus Infections , Cytomegalovirus , Immunity, Innate , Kidney Transplantation , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/prevention & control , Humans , Kidney Transplantation/adverse effects , Cytomegalovirus/immunology , Immunity, Cellular , Natural Killer T-Cells/immunologyABSTRACT
Cytomegalovirus (CMV) has successfully established a long-lasting latent infection in humans due to its ability to counteract the host antiviral innate immune response. During coevolution with the host, the virus has evolved various evasion techniques to evade the host's innate immune surveillance. At present, there is still no vaccine available for the prevention and treatment of CMV infection, and the interaction between CMV infection and host antiviral innate immunity is still not well understood. However, ongoing studies will offer new insights into how to treat and prevent CMV infection and its related diseases. Here, we update recent studies on how CMV evades antiviral innate immunity, with a focus on how CMV proteins target and disrupt critical adaptors of antiviral innate immune signaling pathways. This review also discusses some classic intrinsic cellular defences that are crucial to the fight against viral invasion. A comprehensive review of the evasion mechanisms of antiviral innate immunity by CMV will help investigators identify new therapeutic targets and develop vaccines against CMV infection.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Immune Evasion , Immunity, Innate , Humans , Immunity, Innate/immunology , Cytomegalovirus/immunology , Immune Evasion/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Signal Transduction/immunology , Host-Pathogen Interactions/immunology , Animals , Viral Proteins/immunology , Viral Proteins/metabolismABSTRACT
INTRODUCTION: This prospective cohort study aims to investigate the hearing dynamics and the changes in the central auditory pathways in infants with congenital cytomegalovirus (cCMV) infection. MATERIALS AND METHODS: cCMV-infected neonates aged ≤3 weeks old were recruited and underwent clinical and laboratory tests to detect viremia and symptomatic infection, hearing examinations at three and six months of age, and radiological imaging of brain auditory pathways using diffusion tensor imaging. RESULTS: From 26 eligible infants (52 ears), we detected symptomatic infection in nine (34.6%), viremia in 14 (14/25; 56.0%) and sensorineural hearing loss (SNHL) in 14 infants (53.8%). We observed 40 ears (76.9%) with unstable hearing thresholds, 17 (42.5%) of which fluctuated. Hearing fluctuation and progressivity were more common in symptomatic infection (66.7% vs. 14.7%, p<0.001; and 38.9% vs. 2.9%, p=0.002; respectively). A substantial proportion of ears had reduced fractional anisotropy (FA) in the medial geniculate body (59.1%), superior olivary nucleus (45.5%), trapezoid body (40.9%), auditory radiation (36.4%) and inferior colliculus (31.8%). Symptomatic infection was associated with an increased FA in the medial geniculate body (mean difference, MD: 0.12; 95% Confidence Intervals, 95%CI: 0.03, 0.22) and viremia in the inferior colliculus (MD: 0.09; 95%CI: 0.02, 0.16). An FA in the inferior colliculus of ≥0.404 had a sensitivity and specificity of 68.8% and 83.3% in predicting viremia (area under the curve 0.823; 95%CI: 0.633, 1.000, p=0.022). CONCLUSION: SNHL along with its fluctuation and progression are common in cCMV-infected infants. cCMV infection may induce structural changes in the central auditory pathway.
Subject(s)
Auditory Pathways , Cytomegalovirus Infections , Humans , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnostic imaging , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/physiopathology , Prospective Studies , Female , Male , Infant, Newborn , Auditory Pathways/diagnostic imaging , Auditory Pathways/physiopathology , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/virology , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Sensorineural/diagnostic imaging , Infant , Hearing TestsABSTRACT
Introduction: Human Cytomegalovirus (HCMV) is a betaherpesvirus that causes severe disease in immunocompromised transplant recipients. Immunotherapy with CD8 T cells specific for HCMV antigens presented on HLA class-I molecules is explored as strategy for long-term relief to such patients, but the antiviral effectiveness of T cell preparations cannot be efficiently predicted by available methods. Methods: We developed an Assay for Rapid Measurement of Antiviral T-cell Activity (ARMATA) by real-time automated fluorescent microscopy and used it to study the ability of CD8 T cells to neutralize HCMV and control its spread. As a proof of principle, we used TCR-transgenic T cells specific for the immunodominant HLA-A02-restricted tegumental phosphoprotein pp65. pp65 expression follows an early/late kinetic, but it is not clear at which stage of the virus cycle it acts as an antigen. We measured control of HCMV infection by T cells as early as 6 hours post infection (hpi). Results: The timing of the antigen recognition indicated that it occurred before the late phase of the virus cycle, but also that virion-associated pp65 was not recognized during virus entry into cells. Monitoring of pp65 gene expression dynamics by reporter fluorescent genes revealed that pp65 was detectable as early as 6 hpi, and that a second and much larger bout of expression occurs in the late phase of the virus cycle by 48 hpi. Since transgenic (Tg)-pp65 specific CD8 T cells were activated even when DNA replication was blocked, our data argue that pp65 acts as an early virus gene for immunological purposes. Discussion: ARMATA does not only allow same day identification of antiviral T-cell activity, but also provides a method to define the timing of antigen recognition in the context of HCMV infection.
Subject(s)
CD8-Positive T-Lymphocytes , Cytomegalovirus Infections , Cytomegalovirus , Phosphoproteins , Viral Matrix Proteins , CD8-Positive T-Lymphocytes/immunology , Cytomegalovirus/immunology , Cytomegalovirus/genetics , Phosphoproteins/immunology , Phosphoproteins/genetics , Humans , Viral Matrix Proteins/immunology , Viral Matrix Proteins/genetics , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Gene Expression Regulation, Viral , Antigens, Viral/immunology , HLA-A2 Antigen/immunology , HLA-A2 Antigen/geneticsABSTRACT
To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children's Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA- cohort, 70 (65.4%) in the DNA+ and AVT- cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log-rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5-year NLS of 68.3% in the DNA- cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT- cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5-year NLS and AVT was recommended for CMV-infected BA infants.
Subject(s)
Antiviral Agents , Biliary Atresia , Cytomegalovirus Infections , Cytomegalovirus , Humans , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Retrospective Studies , Biliary Atresia/drug therapy , Antiviral Agents/therapeutic use , Female , Male , Infant , Cytomegalovirus/genetics , Cytomegalovirus/drug effects , Prognosis , DNA, Viral , Infant, NewbornABSTRACT
BACKGROUND: Road traffic injuries (RTIs) are among the most important issues worldwide. Several studies reported that infection with the neurotropic parasite Toxoplasma gondii (T. gondii) increased the risk of car accidents. In this study, our objective was to investigate the possible associations among latent T. gondii, Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV) infections with the risk of motorcycle accidents in Jahrom (Fars Province), which is a county with a high rate of motorcycle accidents in Iran. METHODS: In the setting of a case-control study; 176 motorcyclist men, including 88 survivors of motorcycle accidents and 88 motorcyclist without accidents, were considered as case and control groups, respectively. Rates of latent infections with T. gondii, CMV, and HSV were assessed by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Eleven of 88 (12.5%) in the case group and 22 of 88 (25.0%) in controls were positive for anti-T. gondii IgG antibodies, this difference was statistically significant (OR = 0.42; CI: 0.19-0.95, p = 0.03). The general seroprevalence of CMV (94.3% in the case group vs. 87.5% in the control group, OR = 2.37; CI: 0.78-7.13, p = 0.12) and HSV (63.6% in the case group vs. 62.5% in the control group, OR = 1.05; CI: 0.57-1.94, p = 0.87) were not significantly different between the case and control groups. CONCLUSIONS: Although latent toxoplasmosis has been associated with traffic accidents in recent reports, we found a negative association between latent toxoplasmosis and motorcycle accidents among survivors of these accidents. As such, latent CMV and HSV infections did not differ significantly between the cases compared to the control groups.
Subject(s)
Accidents, Traffic , Cytomegalovirus Infections , Herpes Simplex , Motorcycles , Toxoplasmosis , Humans , Iran/epidemiology , Accidents, Traffic/statistics & numerical data , Case-Control Studies , Male , Toxoplasmosis/epidemiology , Adult , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/complications , Herpes Simplex/epidemiology , Herpes Simplex/complications , Cytomegalovirus , Young Adult , Middle Aged , Simplexvirus/pathogenicity , Toxoplasma , Risk Factors , Latent Infection/epidemiology , AdolescentSubject(s)
Cytomegalovirus Infections , Cytomegalovirus , Humans , Cytomegalovirus Infections/mortality , Cytomegalovirus Infections/epidemiology , United States/epidemiology , Adult , Female , Male , Cytomegalovirus/immunology , Middle Aged , Aged , Seroepidemiologic Studies , Young Adult , Antibodies, Viral/blood , Mortality , Aged, 80 and overABSTRACT
BACKGROUND: The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. CASE PRESENTATION: A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. CONCLUSION: Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.
Subject(s)
Colitis , Cytomegalovirus Infections , Female , Humans , Adult , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Colitis/virology , Colitis/diagnosis , Colitis/complications , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/drug therapy , Cytomegalovirus/isolation & purification , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/diagnosis , Antiviral Agents/therapeutic use , BiopsyABSTRACT
Cytomegalovirus infection contributes to 10-30% of congenital hearing loss in children. Vertebrate peripheral auditory organs include the outer, middle, and inner ear. Their development is regulated by multiple signaling pathways. However, most ear diseases due to viral infections are due to congenital infections and reactivation and affect healthy adults to a lesser extent. This may be due to the fact that viral infections affect signaling pathways that are important for the development of peripheral hearing organs. Therefore, an in-depth understanding of the relationship between viral infections and the signaling pathways involved in the development of peripheral hearing organs is important for the prevention and treatment of ear diseases. In this review, we summarize the effects of viruses on signaling pathways and signaling molecules in the development of peripheral auditory organs.