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1.
Arch Iran Med ; 27(5): 277-286, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690795

RESUMO

Human cytomegalovirus (HCMV) is classified within the Herpesvirales order and is prevalent in 50%‒80% of the general population. Most carriers experience this infection without noticeable clinical symptoms. HCMV causes a lifelong latent infection that can be reactivated due to immune disorders and inflammation. The reactivation of HCMV becomes particularly significant when it coincides with inflammatory bowel disease (IBD). While cytomegalovirus (CMV) colitis in IBD patients was identified years ago, the role of CMV in triggering flare-ups, acute severe colitis, treatment resistance, and other outcomes in IBD patients experiencing CMV reactivation remains a subject of ongoing debate. In this review, we aim to address an updated insight into aspects related to the CMV colitis in IBD patients including epidemiology, risk factors, clinical features, diagnostic tests, histology, place of immunosuppressants and indications for antiviral treatment. We suggest for personalized and thorough assessment based on the disease phase and colitis severity when prescribing drugs to these patients. Furthermore, we emphasize the importance of regular patient follow-up to monitor drug side effects, ensuring treatment success, and minimizing the risk of colectomy.


Assuntos
Antivirais , Infecções por Citomegalovirus , Doenças Inflamatórias Intestinais , Humanos , Infecções por Citomegalovirus/complicações , Doenças Inflamatórias Intestinais/complicações , Antivirais/uso terapêutico , Fatores de Risco , Citomegalovirus , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adulto , Colite/virologia
2.
PLoS Pathog ; 20(5): e1012058, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38768227

RESUMO

Viral disruption of innate immune signaling is a critical determinant of productive infection. The Human Cytomegalovirus (HCMV) UL26 protein prevents anti-viral gene expression during infection, yet the mechanisms involved are unclear. We used TurboID-driven proximity proteomics to identify putative UL26 interacting proteins during infection to address this issue. We find that UL26 forms a complex with several immuno-regulatory proteins, including several STAT family members and various PIAS proteins, a family of E3 SUMO ligases. Our results indicate that UL26 prevents STAT phosphorylation during infection and antagonizes transcriptional activation induced by either interferon α (IFNA) or tumor necrosis factor α (TNFα). Additionally, we find that the inactivation of PIAS1 sensitizes cells to inflammatory stimulation, resulting in an anti-viral transcriptional environment similar to ΔUL26 infection. Further, PIAS1 is important for HCMV cell-to-cell spread, which depends on the presence of UL26, suggesting that the UL26-PIAS1 interaction is vital for modulating intrinsic anti-viral defense.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Proteínas Inibidoras de STAT Ativados , Proteínas Virais , Humanos , Citomegalovirus/imunologia , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteínas Inibidoras de STAT Ativados/genética , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Regulação Viral da Expressão Gênica , Imunidade Inata
3.
Front Immunol ; 15: 1392477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774878

RESUMO

Introduction: Accumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs. Methods: Therefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNÉ£ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs. Results: Robust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination. Discussion: Together, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.


Assuntos
COVID-19 , Reações Cruzadas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Linfócitos T , Humanos , Reações Cruzadas/imunologia , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Idoso , Masculino , Linfócitos T/imunologia , Feminino , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores Etários , Adulto Jovem , Vacinas contra COVID-19/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Imunização Secundária , Citomegalovirus/imunologia , Vacina BNT162/imunologia , Vacinação , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , ChAdOx1 nCoV-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Idoso de 80 Anos ou mais
4.
Front Immunol ; 15: 1389358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736873

RESUMO

Introduction: Polymorphisms in the KIR and HLA genes contribute to the diversity of the NK cell repertoire. Extrinsic factors also play a role in modifying this repertoire. The best example is cytomegalovirus, which promotes the expansion of memory-like NK cells. However, the mechanisms governing this phenotypic structure are poorly understood. Furthermore, the influence of age and sex has been understudied. Methods: In this study, we examined these parameters in a cohort of 200 healthy volunteer blood donors, focusing on the major inhibitory KIR receptors and CD94/NKG2A, as well as the differentiation marker CD57 and the memory-like population marker NKG2C. Flow cytometry and two joint analyses, unsupervised and semi-supervised, helped define the impact of various intrinsic and extrinsic markers on the phenotypic structure of the NK cell repertoire. Results: In the KIR NK cell compartment, the KIR3DL1 gene is crucial, as unexpressed alleles lead to a repertoire dominated by KIR2D interacting only with HLA-C ligands, whereas an expressed KIR3DL1 gene allows for a greater diversity of NK cell subpopulations interacting with all HLA class I ligands. KIR2DL2 subsequently favors the KIR2D NK cell repertoire specific to C1/C2 ligands, whereas its absence promotes the expression of KIR2DL1 specific to the C2 ligand. The C2C2Bw4+ environment, marked by strong -21T motifs, favors the expansion of the NK cell population expressing only CD57, whereas the absence of HLA-A3/A11 ligands favors the population expressing only NKG2A, a population highly represented within the repertoire. The AA KIR genotype favors NK cell populations without KIR and NKG2A receptors, whereas the KIR B+ genotypes favor populations expressing KIR and NKG2A. Interestingly, we showed that women have a repertoire enriched in CD57- NK cell populations, while men have more CD57+ NK cell subpopulations. Discussion: Overall, our data demonstrate that the phenotypic structure of the NK cell repertoire follows well-defined genetic rules and that immunological history, sex, and age contribute to shaping this NK cell diversity. These elements can contribute to the better selection of hematopoietic stem cell donors and the definition of allogeneic NK cells for cell engineering in NK cell-based immunotherapy approaches.cters are displayed correctly.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Genótipo , Células Matadoras Naturais , Receptores KIR , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Feminino , Masculino , Adulto , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/genética , Citomegalovirus/imunologia , Receptores KIR/genética , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Etários , Antígenos CD57 , Teste de Histocompatibilidade , Adulto Jovem , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Antígenos HLA/genética , Antígenos HLA/imunologia , Idoso , Receptores KIR3DL1/genética
5.
Pediatr Infect Dis J ; 43(6): 556-558, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38753994

RESUMO

We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%. Parents of children with moderate/severe outcomes reported strain on all areas of family functioning. Behavioral problems were associated with negative impact on parental feelings and marital/partnership relationship. Our findings inform planning support services.


Assuntos
Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/psicologia , Feminino , Masculino , Pré-Escolar , Criança , Lactente , Inquéritos e Questionários , Comportamento Problema/psicologia , Família/psicologia , Pais/psicologia , Transtornos do Comportamento Infantil , Recém-Nascido , Adolescente
6.
Cells ; 13(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38727277

RESUMO

Assessing immune responses to cytomegalovirus (CMV) after liver transplant in patients on immunosuppressive therapy remains challenging. In this study, employing ELISPOT assays, 52 liver-transplant recipients were evaluated for antiviral T-cell activity in peripheral blood mononuclear cells (PBMCs), measuring interferon-γ (IFN-γ) secretion upon stimulation with CMV-specific peptides (CMV peptide pool, CMV IE-1, and pp65 antigens). Parameters such as stimulation index, mean spot size, and mean spot count were measured. The study found that heightened immunosuppression, especially with prednisolone in triple therapy, significantly dampened CMV-specific immune responses. This was demonstrated by decreased IFN-γ production by CMV-specific T-cells (CMV peptide pool: p = 0.036; OR = 0.065 [95% CI: 0.005-0.840], pp65 antigen: p = 0.026; OR = 0.048 [95% CI: 0.003-0.699]). Increased immunosuppression correlated with reduced IFN-γ secretion per cell, reflected in smaller mean spot sizes for the CMV peptide pool (p = 0.019). Notably, shorter post-transplant intervals correlated with diminished antiviral T-cell IFN-γ release at two years (CMV peptide pool: p = 0.019; IE antigen: p = 0.010) and five years (CMV peptide pool: p = 0.0001; IE antigen: p = 0.002; pp65 antigen: p = 0.047), as did advancing age (pp65 antigen: p = 0.016, OR = 0.932, 95% CI: 0.881-0.987). Patients with undetectable CMV antigens had a notably higher risk of CMV reactivation within six months from blood collection, closely linked with triple immunosuppression and prednisolone use. These findings highlight the intricate interplay between immunosuppression, immune response dynamics, and CMV reactivation risk, emphasizing the necessity for tailored immunosuppressive strategies to mitigate CMV reactivation in liver-transplant recipients. It can be concluded that, particularly in the early months post-transplantation, the use of prednisolone as a third immunosuppressant should be critically reconsidered. Additionally, the use of prophylactic antiviral therapy effective against CMV in this context holds significant importance.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , ELISPOT , Hospedeiro Imunocomprometido , Interferon gama , Transplante de Fígado , Linfócitos T , Humanos , Transplante de Fígado/efeitos adversos , Citomegalovirus/imunologia , Masculino , Feminino , ELISPOT/métodos , Pessoa de Meia-Idade , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Linfócitos T/imunologia , Interferon gama/metabolismo , Interferon gama/imunologia , Idoso , Adulto , Imunossupressores/uso terapêutico , Terapia de Imunossupressão
8.
J Neonatal Perinatal Med ; 17(2): 275-284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728205

RESUMO

BACKGROUND: Pulmonary vascular disease (PVD) is a major determinant of both morbidity and mortality in extremely low birth weight infants. It is biologically plausible that postnatal cytomegalovirus (pCMV) infection may lead to PVD in premature infants secondary to pneumonitis or via derangement of pulmonary vascular development directly through endothelial dysfunction. Uncertainty remains, however, regarding thresholds for intervention in premature infants with cardiorespiratory instability and presumed CMV infection likely secondary to the limited understanding of the natural history of the disease. METHODS/RESULTS: We describe four cases of premature infants with clinical and echocardiography features of PVD, in the setting of postnatally acquired CMV. All patients had atypical PVD trajectories, refractory to vasodilator treatment, which improved after initiation of CMV treatment. CONCLUSION: We highlight the need to consider postnatally acquired CMV infection in patients with PVD non-responsive to standard pulmonary vasodilator therapies or disease severity which is out of proportion of the usual clinical trajectory. Treatment of extremely premature infants with CMV-associated PVD may have positive impact on cardiorespiratory health, although duration of therapy remains uncertain.


Assuntos
Infecções por Citomegalovirus , Lactente Extremamente Prematuro , Humanos , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Recém-Nascido , Feminino , Masculino , Antivirais/uso terapêutico , Vasodilatadores/uso terapêutico , Doenças do Prematuro/virologia , Ecocardiografia/métodos
9.
J Infect Dev Ctries ; 18(4): 565-570, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38728630

RESUMO

INTRODUCTION: Cytomegalovirus (CMV) infection has long been recognized as an important viral syndrome in the immunocompromised host. The disease is less well described in critically-ill patients. We evaluated the risk factors for the development of CMV infection in patients admitted to the intensive care unit (ICU). We also compared the outcomes of CMV infection in ICU patients to those of patients with hematological malignancies. METHODOLOGY: This is a retrospective study composed of three arms: patients admitted to the ICU with infection (ICU + / CMV + arm), patients admitted to the ICU who did not develop CMV infection (ICU + / CMV- arm, and patients with hematological malignancies on the hematology ward without CMV infection (ICU - / CMV + arm). RESULTS: Patients who were admitted to ICU for surgical causes had a decreased risk of CMV infection. On the other hand, receiving corticosteroids and vasoactive drugs was associated with an increased risk of CMV infection with adjusted odds ratios (aOR) of 2.4 and 25.3, respectively. Mortality was higher in ICU + / CMV + patients compared to ICU - / CMV + patients. In the ICU + /CMV + population, male sex and being on mechanical ventilation after CMV infection were independent predictors of mortality (aOR 4.6 and 5.0, respectively). CONCLUSIONS: CMV infection in ICU patients is a potentially serious disease requiring close attention. The findings from our study help in identifying patients in the ICU at risk for CMV infection, thereby warranting frequent screening. Patients at high risk of death (male, on mechanical ventilation) should receive prompt treatment and intensive follow-up.


Assuntos
Infecções por Citomegalovirus , Unidades de Terapia Intensiva , Humanos , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Masculino , Estudos Retrospectivos , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Idoso , Adulto , Estado Terminal
10.
Sci Rep ; 14(1): 10253, 2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704431

RESUMO

The tegument protein pp150 of Human Cytomegalovirus (HCMV) is known to be essential for the final stages of virus maturation and mediates its functions by interacting with capsid proteins. Our laboratory has previously identified the critical regions in pp150 important for pp150-capsid interactions and designed peptides similar in sequence to these regions, with a goal to competitively inhibit capsid maturation. Treatment with a specific peptide (PepCR2 or P10) targeted to pp150 conserved region 2 led to a significant reduction in murine CMV (MCMV) growth in cell culture, paving the way for in vivo testing in a mouse model of CMV infection. However, the general pharmacokinetic parameters of peptides, including rapid degradation and limited tissue and cell membrane permeability, pose a challenge to their successful use in vivo. Therefore, we designed a biopolymer-stabilized elastin-like polypeptide (ELP) fusion construct (ELP-P10) to enhance the bioavailability of P10. Antiviral efficacy and cytotoxic effects of ELP-P10 were studied in cell culture, and pharmacokinetics, biodistribution, and antiviral efficacy were studied in a mouse model of CMV infection. ELP-P10 maintained significant antiviral activity in cell culture, and this conjugation significantly enhanced P10 bioavailability in mouse tissues. The fluorescently labeled ELP-P10 accumulated to higher levels in mouse liver and kidneys as compared to the unconjugated P10. Moreover, viral titers from vital organs of MCMV-infected mice indicated a significant reduction of virus load upon ELP-P10 treatment. Therefore, ELP-P10 has the potential to be developed into an effective antiviral against CMV infection.


Assuntos
Antivirais , Infecções por Citomegalovirus , Elastina , Muromegalovirus , Peptídeos , Fosfoproteínas , Proteínas da Matriz Viral , Animais , Elastina/química , Elastina/metabolismo , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Camundongos , Antivirais/farmacologia , Antivirais/farmacocinética , Antivirais/química , Peptídeos/farmacologia , Peptídeos/química , Muromegalovirus/efeitos dos fármacos , Humanos , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/química , Citomegalovirus/efeitos dos fármacos , Capsídeo/metabolismo , Capsídeo/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/farmacocinética , Modelos Animais de Doenças , Polipeptídeos Semelhantes à Elastina
11.
Zhonghua Nei Ke Za Zhi ; 63(5): 486-489, 2024 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-38715486

RESUMO

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.


Assuntos
Antivirais , Infecções por Citomegalovirus , Linfo-Histiocitose Hemofagocítica , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/virologia , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/diagnóstico , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Adulto Jovem , Idoso , Citomegalovirus , Prognóstico
12.
Ugeskr Laeger ; 186(15)2024 Apr 08.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38708697

RESUMO

Cytomegalovirus infection (CMV) can be fatal for organ transplant recipients as shown in this case report. Maribavir is a recently approved drug, which can be used for therapy-refractory CMV infection or when other treatment options cannot be used. The patient in this case report was a CMV-infected liver transplant recipient, who developed a severe erythema and high CMV DNA during valganciclovir therapy. Toxic epidermal necrolysis was suspected. The patient was treated with maribavir, and both CMV DNA and the skin normalised. This case illustrates that maribavir is a useful alternative to other antiviral drugs for CMV infection.


Assuntos
Antivirais , Infecções por Citomegalovirus , Diclororribofuranosilbenzimidazol/análogos & derivados , Transplante de Fígado , Ribonucleosídeos , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Antivirais/uso terapêutico , Ribonucleosídeos/uso terapêutico , Ribonucleosídeos/administração & dosagem , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Citomegalovirus/isolamento & purificação , Citomegalovirus/efeitos dos fármacos
13.
Front Immunol ; 15: 1386586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779663

RESUMO

Background: Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19. Methods: A multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis. Results: The prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival. Discussion: These findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management. Conclusion: This study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.


Assuntos
COVID-19 , Infecções por Citomegalovirus , Citomegalovirus , SARS-CoV-2 , Sepse , Humanos , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Sepse/imunologia , Sepse/epidemiologia , Sepse/mortalidade , Citomegalovirus/imunologia , Idoso , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/complicações , SARS-CoV-2/imunologia , Fatores de Risco , Adulto , Anticorpos Antivirais/sangue
14.
Medicina (Kaunas) ; 60(5)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38792882

RESUMO

Background and Objectives: The investigation of oncogenic viruses and their potential association with breast cancer (BC) remains an intriguing area of study. The current work aims to assess evidence of three specific viruses, human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in BC samples and to explore their relationship with relevant clinicopathological variables. Materials and Methods: The analysis involved BC samples from 110 Jordanian female patients diagnosed with BC and breast tissue samples from 30 control patients with no evidence of breast malignancy, investigated using real-time PCR. The findings were then correlated with various clinico-pathological characteristics of BC. Results: HPV was detected in 27 (24.5%), CMV in 15 (13.6%), and EBV in 18 (16.4%) BC patients. None of the control samples was positive for HPV or CMV while EBV was detected in only one (3.3%) sample. While (HPV/EBV), (HPV/CMV), and (EBV/CMV) co-infections were reported in 1.8%, 2.7%, and 5.5%, respectively, coinfection with the three viruses (HPV/CMV/EBV) was not reported in our cohort. A statistically significant association was observed between HPV status and age (p = 0.047), and between clinical stage and CMV infection (p = 0.015). Conclusions: Our findings indicate the presence or co-presence of HPV, CMV, and EBV in the BC subpopulation, suggesting a potential role in its development and/or progression. Further investigation is required to elucidate the underlying mechanisms that account for the exact role of oncoviruses in breast carcinogenesis.


Assuntos
Neoplasias da Mama , Citomegalovirus , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Feminino , Neoplasias da Mama/virologia , Jordânia/epidemiologia , Pessoa de Meia-Idade , Herpesvirus Humano 4/isolamento & purificação , Citomegalovirus/isolamento & purificação , Adulto , Idoso , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase em Tempo Real , Papillomavirus Humano
15.
Nat Commun ; 15(1): 4286, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769332

RESUMO

The function and phenotype of γδ T cells in the context of common variable immunodeficiency (CVID) has not been explored. CVID is a primary immunodeficiency disorder characterized by impaired antibody responses resulting in increased susceptibility to infections. γδ T cells are a subset of unconventional T cells that play crucial roles in host defence against infections. In this study, we aim to determine the roles and functions of γδ T cells in CVID. We observe a higher frequency of Vδ1+ γδ T cells compared to healthy controls, particularly in older patients. We also find a higher proportion of effector-memory Vδ1+ γδ T cells and a more clonal T cell receptor (TCR) repertoire in CVID. The most significant driver of the Vδ1+ γδ T cell expansion and phenotype in CVID patients is persistent cytomegalovirus (CMV) viremia. These findings provide valuable insights into γδ T cell biology and their contribution to immune defence in CVID.


Assuntos
Imunodeficiência de Variável Comum , Infecções por Citomegalovirus , Citomegalovirus , Receptores de Antígenos de Linfócitos T gama-delta , Humanos , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/virologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Masculino , Feminino , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Adulto , Citomegalovirus/imunologia , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Subpopulações de Linfócitos T/imunologia , Viremia/imunologia , Adolescente , Estudos de Casos e Controles
16.
Viruses ; 16(5)2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38793653

RESUMO

BACKGROUND: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. METHODS: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. RESULTS: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22-0.84), with significantly higher rates (2.1%, 95% CI 0.58-5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31-4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23-37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). CONCLUSIONS: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Países em Desenvolvimento , Triagem Neonatal , Saliva , Humanos , Saliva/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Recém-Nascido , Feminino , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Estudos Prospectivos , Triagem Neonatal/métodos , Masculino , Técnicas de Diagnóstico Molecular/métodos , Prevalência , Programas de Rastreamento/métodos , Sensibilidade e Especificidade , Gravidez , Fatores de Risco
17.
Viruses ; 16(5)2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38793661

RESUMO

Human cytomegalovirus (CMV) is a common herpesvirus causing lifelong latent infection in most people and is a primary cause of congenital infection worldwide. Given the role of NK cells in the materno-fetal barrier, we investigated peripheral blood NK cell behavior in the context of CMV infection acquired during pregnancy. We analyzed the NK phenotype and CD107a surface mobilization on PBMCs from CMV-transmitting and non-transmitting mothers and newborns with or without congenital infection. NK cells from non-transmitting mothers showed the typical phenotype of CMV-adaptive NK cells, characterized by higher levels of NKG2C, CD57, and KIRs, with reduced NKG2A, compared to transmitting ones. A significantly higher percentage of DNAM-1+, PD-1+, and KIR+NKG2A-CD57+PD-1+ CD56dim cells was found in the non-transmitting group. Accordingly, NK cells from congenital-CMV (cCMV)-infected newborns expressed higher levels of NKG2C and CD57, with reduced NKG2A, compared to non-congenital ones. Furthermore, they showed a significant expansion of CD56dim cells co-expressing NKG2C and CD57 or with a memory-like (KIR+NKG2A-CD57+NKG2C+) phenotype, as well as a significant reduction of the CD57-NKG2C- population. Degranulation assays showed a slightly higher CD107a geomean ratio in NK cells of mothers who were non-transmitting compared to those transmitting the virus. Our findings demonstrate that both CMV-transmitting mothers and cCMV newborns show a specific NK profile. These data can guide studies on predicting virus transmission from mothers and congenital infection in infants.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transmissão Vertical de Doenças Infecciosas , Células Matadoras Naturais , Complicações Infecciosas na Gravidez , Humanos , Células Matadoras Naturais/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/transmissão , Feminino , Gravidez , Recém-Nascido , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/imunologia , Citomegalovirus/imunologia , Adulto , Estudos de Coortes , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Adulto Jovem
18.
Diagn Microbiol Infect Dis ; 109(3): 116301, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723453

RESUMO

Accurate detection and quantification of cytomegalovirus (CMV) is crucial to preventing adverse outcomes in immunocompromised individuals. Current assays were developed for use with plasma specimens, but CMV may be present in bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid (CSF). We evaluated the performance of the Abbott Alinity m CMV assay compared to the Abbott RealTime CMV assay for quantification of CMV in plasma, BAL, and CSF specimens. To evaluate clinical performance, 190 plasma, 78 BAL, and 20 CSF specimens were tested with the Alinity m assay and compared to the RealTime assay. The Alinity m CMV assay showed high precision (SD <0.01 to 0.13) for all 3 specimen types. Clincal plasma and BAL specimens with quantifiable CMV DNA demonstrated strong correlation to RealTime CMV assay results (r2 = 0.9779 for plasma, r2 = 0.9373 for BAL). The Alinity m CMV assay may be useful for quantification of CMV in plasma, BAL, and CSF specimens.


Assuntos
Líquido da Lavagem Broncoalveolar , Líquido Cefalorraquidiano , Infecções por Citomegalovirus , Citomegalovirus , Humanos , Líquido da Lavagem Broncoalveolar/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/líquido cefalorraquidiano , Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , Citomegalovirus/genética , Líquido Cefalorraquidiano/virologia , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Sensibilidade e Especificidade , Carga Viral , Plasma/virologia , DNA Viral/líquido cefalorraquidiano
19.
Transpl Int ; 37: 12712, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784442

RESUMO

Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2 week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing (p = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, p = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety.


Assuntos
Antivirais , Infecções por Citomegalovirus , Transplante de Rim , Valganciclovir , Humanos , Valganciclovir/administração & dosagem , Valganciclovir/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Infecções por Citomegalovirus/prevenção & controle , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Adulto , Idoso , Rim/efeitos dos fármacos , Transplantados
20.
Sci Rep ; 14(1): 11778, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782966

RESUMO

We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , COVID-19/complicações , COVID-19/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante Homólogo/efeitos adversos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Idoso , Infecções por Citomegalovirus/complicações , Estudos Retrospectivos , Adulto Jovem
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