Dataset Information

Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections.

ABSTRACT:

Background

Although most cases of varicella or zoster are self-limited, patients with certain immune deficiencies may develop severe or life-threatening disease.

Methods

We studied a patient with varicella-zoster virus (VZV) central nervous system (CNS) vasculopathy and as part of the evaluation, tested his plasma for antibodies to cytokines. We reviewed the literature for cases of varicella or zoster associated with primary and acquired immunodeficiencies.

Results

We found that a patient with VZV CNS vasculopathy had antibody that neutralized interferon (IFN)-α but not IFN-γ. The patient's plasma blocked phosphorylation in response to stimulation with IFN-α in healthy control peripheral blood mononuclear cells. In addition to acquired immunodeficiencies like human immunodeficiency virus (HIV) or autoantibodies to IFN, variants in specific genes have been associated with severe varicella and/or zoster. Although these genes encode proteins with very different activities, many affect IFN signaling pathways, either those that sense double-stranded RNA or cytoplasmic DNA that trigger IFN production, or those involved in activation of IFN stimulated genes in response to binding of IFN with its receptor.

Conclusions

Immune deficiencies highlight the critical role of IFN in control of VZV infections and suggest new approaches for treatment of VZV infection in patients with certain immune deficiencies.

SUBMITTER: Ansari R

PROVIDER: S-EPMC8563170 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections.

Ansari Rahila R Rosen Lindsey B LB Lisco Andrea A Gilden Don D Holland Steven M SM Zerbe Christa S CS Bonomo Robert A RA Cohen Jeffrey I JI

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20211101 9

<h4>Background</h4>Although most cases of varicella or zoster are self-limited, patients with certain immune deficiencies may develop severe or life-threatening disease.<h4>Methods</h4>We studied a patient with varicella-zoster virus (VZV) central nervous system (CNS) vasculopathy and as part of the evaluation, tested his plasma for antibodies to cytokines. We reviewed the literature for cases of varicella or zoster associated with primary and acquired immunodeficiencies.<h4>Results</h4>We found ...[more]

PMID: 32856043

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Project description:BackgroundPneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP).MethodsThis was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015.ResultsOne hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32-51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1-3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1-2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) = 150 (80-284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33-2.70); p < 0.001), oxygen flow at ICU admission (OR 1.25 (1.08-1.45); p = 0.004), and early bacterial co-infection (OR 14.94 (2.00-111.8); p = 0.009) were independently associated with the need for mechanical ventilation. Duration of mechanical ventilation was 14 (7-21) days. ICU and hospital mortality rates were 17% and 24%, respectively. All patients were treated with aciclovir and 10 received adjunctive therapy with steroids. Compared to 60 matched steroid-free controls, patients treated with steroids had a longer mechanical ventilation duration, ICU length of stay, and a similar hospital mortality, but experienced more ICU-acquired infections.ConclusionsSevere VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection.

Project description:IntroductionMucosal Associated Invariant T (MAIT) cells are innate-like T cells that respond to conserved pathogen-derived vitamin B metabolites presented by the MHC class I related-1 molecule (MR1) antigen presentation pathway. Whilst viruses do not synthesize these metabolites, we have reported that varicella zoster virus (VZV) profoundly suppresses MR1 expression, implicating this virus in manipulation of the MR1:MAIT cell axis. During primary infection, the lymphotropism of VZV is likely to be instrumental in hematogenous dissemination of virus to gain access to cutaneous sites where it clinically manifests as varicella (chickenpox). However, MAIT cells, which are found in the blood and at mucosal and other organ sites, have yet to be examined in the context of VZV infection. The goal of this study was to examine any direct impact of VZV on MAIT cells.MethodsUsing flow cytometry, we interrogated whether primary blood derived MAIT cells are permissive to infection by VZV whilst further analysing differential levels of infection between various MAIT cell subpopulations. Changes in cell surface extravasation, skin homing, activation and proliferation markers after VZV infection of MAIT cells was also assessed via flow cytometry. Finally the capacity of MAIT cells to transfer infectious virus was tested through an infectious center assay and imaged via fluorescence microscopy.ResultsWe identify primary blood-derived MAIT cells as being permissive to VZV infection. A consequence of VZV infection of MAIT cells was their capacity to transfer infectious virus to other permissive cells, consistent with MAIT cells supporting productive infection. When subgrouping MAIT cells by their co- expression of a variety cell surface markers, there was a higher proportion of VZV infected MAIT cells co-expressing CD4+ and CD4+/CD8+ MAIT cells compared to the more phenotypically dominant CD8+ MAIT cells, whereas infection was not associated with differences in co-expression of CD56 (MAIT cell subset with enhanced responsiveness to innate cytokine stimulation), CD27 (co-stimulatory) or PD-1 (immune checkpoint). Infected MAIT cells retained high expression of CCR2, CCR5, CCR6, CLA and CCR4, indicating a potentially intact capacity for transendothelial migration, extravasation and trafficking to skin sites. Infected MAIT cells also displayed increased expression of CD69 (early activation) and CD71 (proliferation) markers.DiscussionThese data identify MAIT cells as being permissive to VZV infection and identify impacts of such infection on co- expressed functional markers.

Dataset Information

Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections.

Background

Methods

Results

Conclusions

Publications

Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections.

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