RESUMEN

Background: Currently, evidence regarding the causal relationship between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome is limited and inconsistent. Therefore, this study employs Mendelian randomization (MR) methodology to investigate the causal relationship between the two. Methods: This study selected 110 single-nucleotide polymorphisms (SNPs) of primary immunodeficiency-related genes as instrumental variables (IVs). Genetic associations of primary immunodeficiency-related genes were derived from recent genome-wide association studies (GWAS) data on human plasma protein levels and circulating immune cells. Data on genes associated with varicella-zoster virus reactivation syndrome were obtained from the GWAS Catalog and FINNGEN database, primarily analyzed using inverse variance weighting (IVW) and sensitivity analysis. Results: Through MR analysis, we identified 9 primary immunodeficiency-related genes causally associated with herpes zoster and its subsequent neuralgia; determined causal associations of 20 primary immunodeficiency-related genes with three vascular lesions (stroke, cerebral aneurysm, giant cell arteritis); revealed causal associations of 10 primary immunodeficiency-related genes with two ocular diseases (retinopathy, keratitis); additionally, three primary immunodeficiency-related genes each were associated with encephalitis, cranial nerve palsy, and gastrointestinal infections. Conclusions: This study discovers a certain association between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome, yet further investigations are warranted to explore the specific mechanisms underlying these connections.

Asunto(s)

Estudio de Asociación del Genoma Completo , Herpesvirus Humano 3 , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Herpesvirus Humano 3/inmunología , Herpes Zóster/genética , Herpes Zóster/inmunología , Herpes Zóster/virología , Activación Viral , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/inmunología , Predisposición Genética a la Enfermedad , Infección por el Virus de la Varicela-Zóster/genética , Infección por el Virus de la Varicela-Zóster/inmunología , Síndromes de Inmunodeficiencia/genética

RESUMEN

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses.

Asunto(s)

Herpesvirus Humano 3 , Células T Invariantes Asociadas a Mucosa , Humanos , Células T Invariantes Asociadas a Mucosa/inmunología , Herpesvirus Humano 3/inmunología , Activación de Linfocitos/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Riboflavina/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Evasión Inmune/inmunología , Herpes Zóster/inmunología , Herpes Zóster/virología

RESUMEN

Varicella zoster virus (VZV) reactivates from ganglionic sensory neurons to produce herpes zoster (shingles) in a unilateral dermatomal distribution, typically in the thoracic region. Reactivation not only heightens the risk of stroke and other neurological complications but also increases susceptibility to co-infections with various viral and bacterial pathogens at sites distant from the original infection. The mechanism by which VZV results in complications remote from the initial foci remains unclear. Small extracellular vesicles (sEVs) are membranous signaling structures that can deliver proteins and nucleic acids to modify the function of distal cells and tissues during normal physiological conditions. Although viruses have been documented to exploit the sEV machinery to propagate infection, the role of non-infectious sEVs released from VZV-infected neurons in viral spread and disease has not been studied. Using multi-omic approaches, we characterized the content of sEVs released from VZV-infected human sensory neurons (VZV sEVs). One viral protein was detected (immediate-early 62), as well as numerous immunosuppressive and vascular disease-associated host proteins and miRNAs that were absent in sEVs from uninfected neurons. Notably, VZV sEVs are non-infectious yet transcriptionally altered primary human cells, suppressing the antiviral type 1 interferon response and promoting neuroinvasion of a secondary pathogen in vivo. These results challenge our understanding of VZV infection, proposing that the virus may contribute to distant pathologies through non-infectious sEVs beyond the primary infection site. Furthermore, this study provides a previously undescribed immune-evasion mechanism induced by VZV that highlights the significance of non-infectious sEVs in early VZV pathogenesis. IMPORTANCE: Varicella zoster virus (VZV) is a ubiquitous human virus that predominantly spreads by direct cell-cell contact and requires efficient and immediate host immune evasion strategies to spread. The mechanisms of immune evasion prior to virion entry have not been fully elucidated and represent a critical gap in our complete understanding of VZV pathogenesis. This study describes a previously unreported antiviral evasion strategy employed by VZV through the exploitation of the infected host cell's small extracellular vesicle (sEV) machinery. These findings suggest that non-infectious VZV sEVs could travel throughout the body, affecting cells remote from the site of infection and challenging the current understanding of VZV clinical disease, which has focused on local effects and direct infection. The significance of these sEVs in early VZV pathogenesis highlights the importance of further investigating their role in viral spread and secondary disease development to reduce systemic complications following VZV infections.

Asunto(s)

Vesículas Extracelulares , Herpesvirus Humano 3 , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/virología , Humanos , Herpes Zóster/virología , Herpes Zóster/inmunología , Animales , MicroARNs/metabolismo , MicroARNs/genética , Células Receptoras Sensoriales/virología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Proteínas Virales/metabolismo , Activación Viral

RESUMEN

BACKGROUND: Varicella-zoster virus (VZV) pretransplant immunization rates, exposures, and posttransplant disease are poorly characterized among pediatric solid organ transplant (SOT) recipients in the two-dose varicella vaccine era. METHODS: A retrospective analysis of the electronic health records among children <18 years old who received SOT from January 1, 2011 through December 31, 2021, was performed at a single center to assess for missed pretransplant varicella vaccination opportunities, characterize VZV exposures, and describe posttransplant disease. RESULTS: Among 525 children, 444 were ≥6 months old (m.o.) at SOT with a documented VZV vaccine status. Eighty-five (19%) did not receive VZV Dose One; 30 out of 85 (35%) could have been immunized. Infants 6-11 m.o. accounted for 14 out of 30 (47%) missed opportunities. Among children ≥12 m.o. with documented Dose Two status (n = 383), 72 had missed vaccination opportunities; 57 out of 72 (79%) were children 1-4 years old. Most children had unclassifiable pre-SOT serostatus as varicella serology was either not obtained/documented (n = 171) or the possibility of passive antibodies was not excluded (n = 137). Of those with classified serology (n = 188), 69 were seroimmune. Forty-seven of 525 (9%) children had recorded VZV exposures; two developed varicella-neither had documented pre-SOT seroimmunity nor had received post-exposure prophylaxis. Nine additional children had medically attended disease: four primary varicella and five zoster. Of the 11 cases, 10 had cutaneous lesions without invasive disease; one had multi-dermatomal zoster with transaminitis. Seven (64%) received treatment exclusively outpatient. CONCLUSIONS: VZV exposure and disease still occur. Optimizing immunization among eligible candidates and ensuring patients have a defined VZV serostatus pretransplantation remain goals of care.

Asunto(s)

Vacuna contra la Varicela , Herpesvirus Humano 3 , Trasplante de Órganos , Humanos , Estudios Retrospectivos , Femenino , Masculino , Preescolar , Niño , Lactante , Vacuna contra la Varicela/administración & dosificación , Vacuna contra la Varicela/inmunología , Trasplante de Órganos/efectos adversos , Adolescente , Herpesvirus Humano 3/inmunología , Varicela/prevención & control , Vacunación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Infección por el Virus de la Varicela-Zóster/inmunología

RESUMEN

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Asunto(s)

Herpesvirus Humano 3 , Humanos , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Herpesvirus Humano 3/patogenicidad , Herpes Zóster/virología , Herpes Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Enfermedades del Sistema Nervioso/virología , Enfermedades del Sistema Nervioso/inmunología , Enfermedades del Sistema Nervioso/etiología , Animales , Varicela/virología , Varicela/inmunología , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/virología

RESUMEN

During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread.

Asunto(s)

Adhesión Celular , Herpesvirus Humano 3 , Molécula 1 de Adhesión Intercelular , Interferón gamma , Queratinocitos , Linfocitos T , Humanos , Interferón gamma/metabolismo , Interferón gamma/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/virología , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Queratinocitos/virología , Queratinocitos/metabolismo , Queratinocitos/inmunología , Herpesvirus Humano 3/fisiología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Leucocitos Mononucleares/virología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Proteínas del Envoltorio Viral/metabolismo , Antígeno-1 Asociado a Función de Linfocito/metabolismo

RESUMEN

Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.

Asunto(s)

Herpesvirus Humano 3 , Transducción de Señal , Piel , Infección por el Virus de la Varicela-Zóster , Herpesvirus Humano 3/genética , Piel/patología , Piel/virología , Piel/inmunología , Animales , Infección por el Virus de la Varicela-Zóster/virología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/genética , Infección por el Virus de la Varicela-Zóster/patología , Humanos , Ratones , Células Dendríticas/inmunología , Herpes Zóster/virología , Herpes Zóster/patología , Herpes Zóster/genética , Herpes Zóster/inmunología , Transcriptoma , Modelos Animales de Enfermedad , Antígenos Virales/inmunología , Antígenos Virales/genética , FN-kappa B/metabolismo , FN-kappa B/genética

RESUMEN

To determine whether there is a correlation between myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases and varicella zoster virus (VZV) infection. We provide a case report and performed a study to determine the frequency of MOG antibodies (MOG-IgG) in neurological VZV infections. Patients admitted to the Medical University of Innsbruck from 2008-2020 with a diagnosis of a neurological manifestation of VZV infection (n=59) were included in this study; patients with neuroborreliosis (n=34) served as control group. MOG-IgG was detected using live cell-based assays. In addition, we performed a literature review focusing on MOG and aquaporin-4 (AQP4) antibodies and their association with VZV infection. Our case presented with VZV-associated longitudinally extensive transverse myelitis and had MOG-IgG at a titer of 1:1280. In the study, we did not detect MOG-IgG in any other patient neither in the VZV group (including 15 with VZV encephalitis/myelitis) nor in the neuroborreliosis group. In the review of the literature, 3 cases with MOG-IgG and additional 9 cases with AQP4 IgG associated disorders in association with a VZV infection were identified. MOG-IgG are rarely detected in patients with VZV infections associated with neurological diseases.

Asunto(s)

Autoanticuerpos/inmunología , Herpesvirus Humano 3/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Mielitis Transversa/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Adulto , Anciano , Acuaporina 4/inmunología , Encefalitis/diagnóstico , Encefalitis/inmunología , Femenino , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/fisiología , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Mielitis Transversa/diagnóstico , Estudios Retrospectivos , Literatura de Revisión como Asunto , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/virología

RESUMEN

RATIONALE: Primary varicella-zoster virus (VZV) infection may be associated with hemophagocytic lymphohistiocytosis (HLH), as well as with acute pancreatitis. However, there is few data concerning the evolution and the optimal treatment of these rare associations. PATIENT CONCERNS: A 57-year-old immunocompromised woman, who was treated for chronic lymphocytic leukemia 3 years prior to admission, was hospitalized with abdominal pain revealing severe acute pancreatitis. The day after admission, a pruritic rash appeared on her face, trunk, and limbs, sparing the palmoplantar regions. At the same time, fever, thrombocytopenia (27 × 109/L), major hyperferritinemia (11,063 µg/mL), hypertriglyceridemia (2.56 mmol/L) and elevated lactate dehydrogenase levels (1441 IU/L) suggested HLH. DIAGNOSIS: The diagnosis of chickenpox (varicella) was established. Primary VZV infection was then confirmed: cutaneous and plasma VZV polymerase chain reactions were positives, VZV serology was negative for IgG. INTERVENTIONS: Treatment with aciclovir was started intravenously after the onset of the rash, for a total of 10 days. A 48-h surveillance in intensive care was carried out. OUTCOMES: Acute pancreatitis and biological abnormalities evolved favorably under aciclovir. Platelet count was normalized 6 days after admission to hospital. LESSONS: A favorable outcome of primary VZV infection associated with severe acute pancreatitis and probable HLH in an immunocompromised patient is possible with aciclovir alone.

Asunto(s)

Herpesvirus Humano 3/inmunología , Huésped Inmunocomprometido/inmunología , Linfohistiocitosis Hemofagocítica/inmunología , Pancreatitis/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Enfermedad Aguda , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/virología , Persona de Mediana Edad , Pancreatitis/virología , Infección por el Virus de la Varicela-Zóster/virología

RESUMEN

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1ß, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1ß+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1ß+ CD14+ monocytes were significant mediators of the associations between IL-1ß and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1ß+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.

Asunto(s)

Herpes Zóster/inmunología , Herpesvirus Humano 3/inmunología , Interleucina-1beta/inmunología , Monocitos/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Anciano de 80 o más Años , Linfocitos B/inmunología , Citocinas/inmunología , Femenino , Herpes Zóster/virología , Humanos , Memoria Inmunológica/inmunología , Inflamación/inmunología , Inflamación/virología , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Masculino , Casas de Salud , Linfocitos T/inmunología , Vacunación/métodos , Vacunas Atenuadas/inmunología , Infección por el Virus de la Varicela-Zóster/virología

RESUMEN

BACKGROUND: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes. CONCLUSIONS: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.

Asunto(s)

Vacuna contra el Herpes Zóster/administración & dosificación , Herpesvirus Humano 3/inmunología , Inmunogenicidad Vacunal , Trasplante de Órganos , Infección por el Virus de la Varicela-Zóster/prevención & control , Adulto , Anticuerpos Antivirales/sangre , Biomarcadores/sangre , Femenino , Vacuna contra el Herpes Zóster/efectos adversos , Herpesvirus Humano 3/patogenicidad , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Inmunización , Masculino , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , Prueba de Estudio Conceptual , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Vacunas Sintéticas/administración & dosificación , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Proteínas del Envoltorio Viral/inmunología

RESUMEN

Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.

Asunto(s)

Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Herpesvirus Humano 3/fisiología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Antígenos CD20/inmunología , Linfocitos B/inmunología , Humanos , Inmunidad Humoral , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Activación Viral , Latencia del Virus

RESUMEN

Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) and shingles (zoster). Although considered benign diseases, both varicella and zoster can cause complications. Zoster is painful and can lead to post herpetic neuralgia. VZV has also been linked to stroke, related to giant cell arteritis in some cases. Vaccines are available but the attenuated vaccine is not recommended in immunocompromised individuals and the efficacy of the glycoprotein E (gE) based subunit vaccine has not been evaluated for the prevention of varicella. A hallmark of VZV pathology is the formation of multinucleated cells termed polykaryocytes in skin lesions. This cell-cell fusion (abbreviated as cell fusion) is mediated by the VZV glycoproteins gB, gH and gL, which constitute the fusion complex of VZV, also needed for virion entry. Expression of gB, gH and gL during VZV infection and trafficking to the cell surface enables cell fusion. Recent evidence supports the concept that cellular processes are required for regulating cell fusion induced by gB/gH-gL. Mutations within the carboxyl domains of either gB or gH have profound effects on fusion regulation and dramatically restrict the ability of VZV to replicate in human skin. This loss of regulation modifies the transcriptome of VZV infected cells. Furthermore, cellular proteins have significant effects on the regulation of gB/gH-gL-mediated cell fusion and the replication of VZV, exemplified by the cellular phosphatase, calcineurin. This review provides the current state-of-the-art knowledge about the molecular controls of cell fusion-dependent pathogenesis caused by VZV.

Asunto(s)

Herpesvirus Humano 3/inmunología , Interacciones Huésped-Patógeno , Infección por el Virus de la Varicela-Zóster/virología , Proteínas del Envoltorio Viral/metabolismo , Internalización del Virus , Animales , Fusión Celular , Vacuna contra la Varicela , Dimerización , Regulación Viral de la Expresión Génica , Herpesvirus Humano 3/genética , Humanos , Inmunoglobulina E/química , Glicoproteínas de Membrana/metabolismo , Ratones , Mutagénesis , Mutación , Sistemas de Lectura Abierta , Conformación Proteica , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/prevención & control , Proteínas Virales/metabolismo , Virión/metabolismo

RESUMEN

Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus-infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection.

Asunto(s)

Herpesvirus Humano 3/inmunología , Sustancia P/genética , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/veterinaria , Activación Viral/inmunología , Animales , Biomarcadores/sangre , Expresión Génica , Herpesvirus Humano 3/patogenicidad , Inmunosupresores/administración & dosificación , Inflamación , Macaca mulatta , Masculino , Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/veterinaria , Sustancia P/sangre , Sustancia P/inmunología , Tacrolimus/administración & dosificación , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/genética , Irradiación Corporal Total

RESUMEN

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.

Asunto(s)

Aterosclerosis/epidemiología , Infecciones/epidemiología , Accidente Cerebrovascular/epidemiología , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/fisiopatología , Aterosclerosis/inmunología , Aterosclerosis/fisiopatología , Bacteriemia/epidemiología , Bacteriemia/inmunología , Bacteriemia/fisiopatología , Betacoronavirus , COVID-19 , Enfermedad Crónica , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/fisiopatología , Endotelio/fisiopatología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/fisiopatología , Humanos , Huésped Inmunocomprometido/inmunología , Infecciones/inmunología , Infecciones/fisiopatología , Inflamación/inmunología , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Humana/fisiopatología , Pandemias , Activación Plaquetaria , Agregación Plaquetaria , Neumonía/epidemiología , Neumonía/inmunología , Neumonía/fisiopatología , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/fisiopatología , Pronóstico , Factores de Riesgo , SARS-CoV-2 , Accidente Cerebrovascular/inmunología , Trombosis/epidemiología , Trombosis/inmunología , Infección por el Virus de la Varicela-Zóster/epidemiología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/fisiopatología

RESUMEN

Myocarditis is a serious complication of varicella zoster virus infection. A 15 year-old boy was admitted to the Emergency Department for chest pain, tachycardia and hypotension. An electrocardiogram showed sinus tachyicardia. Cardiac biomarkers were elevated and echocardiography revealed left ventricular apical, inferolateral, septal hypokinesis, and mitral regurgitation. Varicella zoster virus serum immunoglobulin M antibody was positive. The patient was discharged without any sequelae.

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La miocarditis es una complicación grave de la infección por el virus de la varicela-zóster. Un varón de 15 años ingresó a la sala de emergencias debido a dolor torácico, taquicardia e hipotensión. En el electrocardiograma se observó taquicardia sinusal. Los biomarcadores cardíacos estaban elevados. En el ecocardiograma se notó hipocinesia apical, septal, e inferolateral del ventrículo izquierdo e insuficiencia mitral. Los anticuerpos IgM en suero para el virus de la varicela-zóster eran positivos. El paciente recibió el alta sin secuelas.

Asunto(s)

Miocarditis/virología , Infección por el Virus de la Varicela-Zóster/complicaciones , Enfermedad Aguda , Adolescente , Electrocardiografía , Humanos , Inmunocompetencia , Masculino , Miocarditis/diagnóstico , Miocarditis/inmunología , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/inmunología

RESUMEN

OBJECTIVES: Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN). METHODS: Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0-90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model. RESULTS: Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households. CONCLUSIONS: VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions.

Asunto(s)

Herpesvirus Humano 3 , Infección por el Virus de la Varicela-Zóster/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Niño , Preescolar , Susceptibilidad a Enfermedades , Femenino , Herpesvirus Humano 3/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lactante , Recién Nacido , Islas , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Seroepidemiológicos , Encuestas y Cuestionarios , Vacunas Virales , Adulto Joven

Asunto(s)

Anticuerpos Monoclonales Humanizados/farmacología , Linfocitos B/efectos de los fármacos , Factores Inmunológicos/farmacología , Esclerosis Múltiple/tratamiento farmacológico , Linfocitos T/efectos de los fármacos , Infección por el Virus de la Varicela-Zóster/inmunología , Adulto , Femenino , Humanos , Adulto Joven

Asunto(s)

Dolor Abdominal/tratamiento farmacológico , Aciclovir/administración & dosificación , Exantema/tratamiento farmacológico , Infecciones por VIH/inmunología , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Dolor Abdominal/inmunología , Dolor Abdominal/virología , Administración Intravenosa , Adulto , Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Exantema/inmunología , Exantema/virología , Femenino , Fiebre , Infecciones por VIH/tratamiento farmacológico , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Huésped Inmunocomprometido/inmunología , Hígado/patología , Hígado/virología , Resultado del Tratamiento , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología

Asunto(s)

Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Accidente Cerebrovascular/etiología , Infección por el Virus de la Varicela-Zóster/complicaciones , Vasculitis del Sistema Nervioso Central/complicaciones , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Antivirales/uso terapéutico , Angiografía por Tomografía Computarizada , Disartria/etiología , Humanos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Paresia/etiología , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/inmunología , Vasculitis del Sistema Nervioso Central/diagnóstico , Vasculitis del Sistema Nervioso Central/tratamiento farmacológico , Vasculitis del Sistema Nervioso Central/inmunología