Michael Huber

University of Zurich

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Alexandra Trkola

University of Zurich

Huldrych F. Günthard

University of Zurich

Roger D. Kouyos

University Hospital of Zurich

Dominique L. Braun

University Hospital of Zurich

Enos Bernasconi

Ente Ospedaliero Cantonale

Hans H. Hirsch

University of Basel

Karin J. Metzner

University of Zurich

Jürg Böni

University of Zurich

Sabine Yerly

University of Geneva

Alexandra Calmy

University Hospital of Geneva

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ICE volume 43 issue 3 Cover and Front matter

Infection Control and Hospital Epidemiology (2022)

Marya D. Zilberberg Brian H. Nathanson Laura Puzniak Andrew F. Shorr Blaine Kenaa

An abstract is not available for this content so a preview has been provided. As you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Front cover

10.1017/ice.2022.74

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Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies

The Journal of Experimental Medicine (2024)

Sonja Fernbach Nina K. Mair Irène A. Abela Kevin Groen Roger Kuratli

Autoantibodies neutralizing type I interferons (IFN-Is) can underlie infection severity. Here, we trace the development of these autoantibodies at high-resolution using longitudinal samples from 1,876 well-treated individuals living with HIV over a 35-year period. Similar to general populations, ∼1.9% of individuals acquired anti-IFN-I autoantibodies as they aged (median onset ∼63 years). Once detected, anti-IFN-I autoantibodies persisted lifelong, and titers increased over decades. Individuals developed distinct neutralizing and non-neutralizing autoantibody repertoires at discrete times that selectively targeted combinations of IFNα, IFNβ, and IFNω. Emergence of neutralizing anti-IFNα autoantibodies correlated with reduced baseline IFN-stimulated gene levels and was associated with subsequent susceptibility to severe COVID-19 several years later. Retrospective measurements revealed enrichment of pre-existing autoreactivity against other autoantigens in individuals who later developed anti-IFN-I autoantibodies, and there was evidence for prior viral infections or increased IFN at the time of anti-IFN-I autoantibody triggering. These analyses suggest that age-related loss of self-tolerance prior to IFN-I immune-triggering poses a risk of developing lifelong functional IFN-I deficiency.

Interferon type I

10.1084/jem.20240365

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Charakterisierung von miRNAs als Modulatoren des TLR4-abhängigen MAPK Signalwegs

Rebecca De Santis Ralph Panstruga Dirk H. Ostareck Michael Huber

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2G12-Expressing B Cell Lines May Aid in HIV Carbohydrate Vaccine Design Strategies

Journal of Virology (2012)

Katie J. Doores Michael Huber Khoa Le Sheng‐Kai Wang Colleen Doyle-Cooper

The highly conserved cluster of high-mannose glycans on the HIV-1 envelope glycoprotein, gp120, has been highlighted as a target for neutralizing antibodies. 2G12, the first HIV-1 antiglycan neutralizing antibody described, binds with an unusual domain-exchanged structure that creates a high-affinity multivalent binding surface. It is an interesting challenge for rational vaccine design to generate immunogens capable of eliciting domain-exchanged 2G12-like responses. We recently showed that di-mannose recognition by the variable domains of 2G12 is independent of domain exchange but that exchange is critical for virus neutralization. Carbohydrate-based immunogens aimed at inducing 2G12-like antibodies may need to drive both di-mannose recognition and domain exchange through interactions with B cell receptors. Here we assessed the ability of such immunogens to activate mouse B cell lines displaying domain-exchanged wild-type 2G12 (2G12 WT), a non-domain-exchanged Y-shaped variant (2G12 I19R), and germ line 2G12 (2G12 gl). We show that several immunogens, including heat-killed yeast and bacteria, can activate both 2G12 WT and 2G12 I19R B cells. However, only discrete clusters of high-mannose glycans, as on recombinant forms of the HIV-1 envelope trimer and oligodendrons, activate 2G12 WT B cells. Furthermore, no immunogen tested activated 2G12 gl cells. Our results support the hypothesis that in order to drive domain exchange of an antimannose antibody response, a boost with an immunogen displaying discrete clusters of high-mannose glycans not recognized by conventional Y-shaped antibodies will be required. Additionally, a molecule capable of activating 2G12 gl cells might also be required. The results highlight broadly neutralizing antibody-expressing mouse B cells as potentially useful tools for carbohydrate immunogen screening.

HIV vaccine

10.1128/jvi.02820-12

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Modeling the Spread and Prevention of Malaria in Central America [FULL TEXT]

Michael Huber

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Comparison of analytical sensitivity and efficiency for SARS-CoV-2 primer sets by TaqMan-based and SYBR Green-based RT-qPCR

Applied Microbiology and Biotechnology (2022)

Yile Tao Yang Yue Guangyu Qiu Zheng Ji Martin Spillman

The pandemic of coronavirus disease 2019 (COVID-19) continues to threaten public health. For developing countries where vaccines are still in shortage, cheaper alternative molecular methods for SARS-CoV-2 identification can be crucial to prevent the next wave. Therefore, 14 primer sets recommended by the World Health Organization (WHO) was evaluated on testing both clinical patient and environmental samples with the gold standard diagnosis method, TaqMan-based RT-qPCR, and a cheaper alternative method, SYBR Green-based RT-qPCR. Using suitable primer sets, such as ORF1ab, 2019_nCoV_N1 and 2019_nCoV_N3, the performance of the SYBR Green approach was comparable or better than the TaqMan approach, even when considering the newly dominating or emerging variants, including Delta, Eta, Kappa, Lambda, Mu, and Omicron. ORF1ab and 2019_nCoV_N3 were the best combination for sensitive and reliable SARS-CoV-2 molecular diagnostics due to their high sensitivity, specificity, and broad accessibility. KEY POINTS: • With suitable primer sets, the SYBR Green method performs better than the TaqMan one. • With suitable primer sets, both methods should still detect the new variants well. • ORF1ab and 2019_nCoV_N3 were the best combination for SARS-CoV-2 detection.

TaqMan

Primer (cosmetics)

Gold standard (test)

Taq polymerase

10.1007/s00253-022-11822-4

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Increasing Frequency and Transmission of HIV-1 Non-B Subtypes Among Men Who Have Sex With Men in the Swiss HIV Cohort Study

The Journal of Infectious Diseases (2021)

Jessy J. Duran Ramirez Tala Ballouz Huyen Nguyen Katharina Kusejko Sandra E Chaudron

Abstract Background In Switzerland, HIV-1 transmission among men who have sex with men (MSM) has been dominated by subtype B, whilst non-B subtypes are commonly attributed to infections acquired abroad among heterosexuals. Here, we evaluated the temporal trends of non-B subtypes and the characteristics of molecular transmission clusters (MTCs) among MSM. Methods Sociodemographic and clinical data and partial pol sequences were obtained from participants enrolled in the Swiss HIV Cohort Study. For non-B subtypes, maximum likelihood trees were constructed, from which Swiss MTCs were identified and analyzed by transmission group. Results Non-B subtypes were identified in 8.1% (416/5116) of MSM participants. CRF01_AE was the most prevalent strain (3.5%), followed by subtype A (1.2%), F (1.1%), CRF02_AG (1.1%), C (0.9%), and G (0.3%). Between 1990 and 2019, an increase in the proportion of newly diagnosed individuals (0/123 [0%] to 11/32 [34%]) with non-B subtypes in MSM was found. Across all non-B subtypes, the majority of MSM MTCs were European. Larger MTCs were observed for MSM than heterosexuals. Conclusions We found a substantial increase in HIV-1 non-B subtypes among MSM in Switzerland and the occurrence of large MTCs, highlighting the importance of molecular surveillance in guiding public health strategies targeting the HIV-1 epidemic.

10.1093/infdis/jiab360

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Large and Small Cerebral Vessel Involvement in Severe COVID-19

Stroke (2020)

E. Keller Giovanna Brandi Sebastian Winklhofer Lukas L. Imbach Daniel S. Kirschenbaum

Background and Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Stroke

10.1161/strokeaha.120.031224

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Chinese hamster ovary cells are non-permissive towards infection with coxsackievirus B3 despite functional virus-receptor interactions

Virus Research (1997)

B Kramer Michael Huber Christopher Kern Karin Klingel Reinhard Kandolf

Coxsackievirus

10.1016/s0168-1702(96)01438-4

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Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure

Journal of Clinical Virology (2020)

F. Xavier López‐Labrador Julianne R. Brown Nicole Fischer Heli Harvala Sander van Boheemen

Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols.

10.1016/j.jcv.2020.104691

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