Identifying target cells for a #tick-borne virus that causes #fatal #hemorrhagic fever (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Identifying target cells for a tick-borne virus that causes fatal hemorrhagic fever

Satoko Yamaoka, Carla Weisend, and Hideki Ebihara

First published January 6, 2020

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease in China, South Korea, and Japan caused by the tick-borne SFTS virus (SFTSV). Severe and fatal SFTS presents as a hemorrhagic fever characterized by high viral load, uncontrolled inflammatory response, dysregulated adaptive immunity, coagulation abnormalities, hemorrhage, and multiorgan failure with up to 33% case fatality rates (CFRs). Despite its public health significance in Asia, vaccines and specific therapeutics against SFTS are still unavailable. A better understanding of the pathogenesis of SFTS is crucial to improving medical countermeasures against this devastating disease. In this issue of the JCI, Suzuki and colleagues analyzed histopathological samples from 22 individuals who succumbed to SFTS, and identified antibody-producing B cell–lineage plasmablasts and macrophages as principal target cells for SFTSV infection in fatal SFTS. Their results suggest that SFTSV-infected post–germinal center B cells, plasmablasts, and macrophages affect systemic immunopathology and dysregulation, which likely leads to fatal outcomes.

Keywords: SFTS; Immunopathology; Viral pathogenesis.

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#SFTS virus targets B cells in lethal #human #infections (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

Tadaki Suzuki,1 Yuko Sato,1 Kaori Sano,1,2 Takeshi Arashiro,1 Harutaka Katano,1 Noriko Nakajima,1 Masayuki Shimojima,4 Michiyo Kataoka,1 Kenta Takahashi,1 Yuji Wada,1 Shigeru Morikawa,3 Shuetsu Fukushi,4 Tomoki Yoshikawa,4 Masayuki Saijo,4 and Hideki Hasegawa1,2,5

First published January 6, 2020

Related article: Identifying target cells for a tick-borne virus that causes fatal hemorrhagic fever, Satoko Yamaoka, … , Carla Weisend, Hideki Ebihara

Category: Commentary

 

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne banyangvirus and is associated with high fatality. Despite increasing incidence of SFTS and serious public health concerns in East Asia, the pathogenesis of lethal SFTS virus (SFTSV) infection in humans is not fully understood. Numbers of postmortem examinations to determine target cells of the viral infection have so far been limited. Here we showed that B cells differentiating into plasmablasts and macrophages in secondary lymphoid organs were targets for SFTSV at the end stage of lethal infection, and the majority of SFTSV-infected cells were B cell–lineage lymphocytes. In affected individuals, B cell–lineage lymphocytes with SFTSV infection were widely distributed in both lymphoid and nonlymphoid organs, and infiltration of these cells into the capillaries of the organs could be observed occasionally. Moreover, a human plasmablastic lymphoma cell line, PBL-1, was susceptible to SFTSV propagation, and had a similar immunophenotype to that of target cells of SFTSV in fatal SFTS. PBL-1 can therefore provide a potential in vitro model for human SFTSV infection. These results extend our understanding of the pathogenesis of human lethal SFTSV infection, and can facilitate the development of SFTSV countermeasures.

Keywords: SFTS; Immunopathology; Viral pathogenesis.

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Control of #Nipah Virus #Infection in Mice by the Host Adaptors Mitochondrial Antiviral Signaling Protein (#MAVS) and Myeloid Differentiation Primary Response 88 (MyD88) (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Control of Nipah Virus Infection in Mice by the Host Adaptors Mitochondrial Antiviral Signaling Protein (MAVS) and Myeloid Differentiation Primary Response 88 (MyD88)

Mathieu Iampietro, Noemie Aurine, Kevin P Dhondt, Claire Dumont, Rodolphe Pelissier, Julia Spanier, Audrey Vallve, Herve Raoul, Ulrich Kalinke, Branka Horvat

The Journal of Infectious Diseases, jiz602, https://doi.org/10.1093/infdis/jiz602

Published: 19 December 2019

 

Abstract

Interferon (IFN) type I plays a critical role in the protection of mice from lethal Nipah virus (NiV) infection, but mechanisms responsible for IFN-I induction remain unknown. In the current study, we demonstrated the critical role of the mitochondrial antiviral signaling protein signaling pathway in IFN-I production and NiV replication in murine embryonic fibroblasts in vitro, and the redundant but essential roles of both mitochondrial antiviral signaling protein and myeloid differentiation primary response 88 adaptors, but not TRIF (Toll/Interleukin-1 receptor/Resistance [TIR] domain–containing adaptor–inducing IFN-β), in the control of NiV infection in mice. These results reveal potential novel targets for antiviral intervention and help in understanding NiV immunopathogenesis.

Nipah virus, innate immunity, mice, MAVS, MyD88, TRIF, TLR, interferon

Issue Section: Supplement Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Nipah virus; Immunopathology; Interferons; Animal models.

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Human Immunodeficiency Virus (#HIV)–Infected CCR6+ #Rectal CD4+ T Cells and HIV #Persistence On #Antiretroviral Therapy (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Human Immunodeficiency Virus (HIV)–Infected CCR6+ Rectal CD4+ T Cells and HIV Persistence On Antiretroviral Therapy

Jenny L Anderson, Gabriela Khoury, Rémi Fromentin, Ajantha Solomon, Nicolas Chomont, Elizabeth Sinclair, Jeffrey M Milush, Wendy Hartogensis, Peter Bacchetti, Michael Roche, Carolin Tumpach, Matthew Gartner, Matthew C Pitman, Christine Lorrie Epling, Rebecca Hoh, Frederick M Hecht, Ma Somsouk, Paul U Cameron, Steven G Deeks, Sharon R Lewin

The Journal of Infectious Diseases, jiz509, https://doi.org/10.1093/infdis/jiz509

Published: 04 December 2019

 

Abstract

Background

Identifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy.

Methods

Cell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry.

Results

Integrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines.

Conclusions

HIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues.

HIV reservoir, latency, persistence, chemokine receptor, CCR6, CXCR3, chemokines, rectal tissue, lymph node

Issue Section: Major Article

Keywords: HIV/AIDS; Antivirals; Immunopathology.

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Long-Term #Complications of #Ebola Virus Disease: #Prevalence and #Predictors of Major #Symptoms and the Role of #Inflammation (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 Nov 6. pii: ciz1062. doi: 10.1093/cid/ciz1062. [Epub ahead of print]

Long-Term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation.

Tozay S1, Fischer WA2,3, Wohl DA3,4, Kilpatrick K5, Zou F5, Reeves E1, Pewu K1, DeMarco J3, Loftis AJ3,4, King K3, Grant D3, Schieffelin J3, Gorvego G1, Johnson H1, Conneh T1, Williams G1, Nelson JAE6, Hoover D7, McMillian D3, Merenbloom C3, Hawks D3, Dube K3, Brown J1.

Author information: 1 Eternal Love Winning Africa Hospital, Paynesville, Liberia. 2 Division of Pulmonary and Critical Care Medicine, The University of North Carolina, Chapel Hill, North Carolina, United States of America. 3 The Institute of Global Health and Infectious Diseases, The University of North Carolina, Chapel Hill, North Carolina, United States of America. 4 Division of Infectious Diseases, The University of North Carolina, Chapel Hill, North Carolina, United States of America. 5 Department of Biostatistics, The University of North Carolina, Chapel Hill, North Carolina, United States of America. 6 Department of Microbiology and Immunology, The University of North Carolina, Chapel Hill, North Carolina, United States of America. 7 ICON Government and Public Health Solutions (formerly Clinical RM), Leopardstown, Dublin, Ireland.

 

Abstract

BACKGROUND:

Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola Virus Disease (EVD) survivors; however, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms.

METHODS:

The presence and patterns of eight cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors participating in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation.

RESULTS:

At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least one new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up.

CONCLUSIONS:

Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: Ebola virus disease; Inflammation; Post-EVD Complications; Survivors

PMID: 31693114 DOI: 10.1093/cid/ciz1062

Keywords: Ebola; Immunopathology.

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#Measles virus #infection diminishes preexisting #antibodies that offer #protection from other #pathogens (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Michael J. Mina1,2,3,*,†, Tomasz Kula1,2, Yumei Leng1, Mamie Li2, Rory D. de Vries4, Mikael Knip5,6, Heli Siljander5,6, Marian Rewers7, David F. Choy8, Mark S. Wilson8, H. Benjamin Larman9, Ashley N. Nelson10,‡, Diane E. Griffin10, Rik L. de Swart4, Stephen J. Elledge1,2,11,†

1 Division of Genetics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA. 2 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 3 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 4 Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, 3015 CN, Rotterdam, Netherlands. 5 Children’s Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland. 6 Research Program for Clinical and Molecular Metabolism, University of Helsinki, 00014 Helsinki, Finland. 7 Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Denver, CO 80045, USA. 8 Genentech Inc., South San Francisco, CA 94080, USA. 9 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. 10 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. 11 Program in Virology, Harvard Medical School, Boston, MA 02115, USA.

†Corresponding author. Email: selledge@genetics.med.harvard.edu (S.J.E.); mmina@hsph.harvard.edu (M.J.M.)

* Present address: Center for Communicable Disease Dynamics, Department of Epidemiology and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

‡ Present address: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.

Science  01 Nov 2019: Vol. 366, Issue 6465, pp. 599-606 / DOI: 10.1126/science.aay6485

 

The toll of measles on the immune system

Many of the deaths attributable to measles virus are caused by secondary infections because the virus infects and functionally impairs immune cells. Whether measles infection causes long-term damage to immune memory has been unclear. This question has become increasingly important given the resurgence in measles epidemics worldwide. Using a blood test called VirScan, Mina et al. comprehensively analyzed the antibody repertoire in children before and after natural infection with measles virus as well as in children before and after measles vaccination. They found that measles infection can greatly diminish previously acquired immune memory, potentially leaving individuals at risk for infection by other pathogens. These adverse effects on the immune system were not seen in vaccinated children.

Science, this issue p. 599

 

Abstract

Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.

Keywords: Measles; Immunopathology.

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#Cytokine Induction in #Nipah Virus–Infected Primary #Human and #Porcine #Bronchial Epithelial Cells (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Cytokine Induction in Nipah Virus–Infected Primary Human and Porcine Bronchial Epithelial Cells

Mareike Elvert, Lucie Sauerhering, Andrea Maisner

The Journal of Infectious Diseases, jiz455, https://doi.org/10.1093/infdis/jiz455

Published: 30 October 2019

 

Abstract

During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to an effective virus replication and associated inflammation processes in the porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infections resulted in the expression of type III interferons (IFN-λ). Upon infections with similar virus doses, the viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed a reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of the antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.

Nipah virus, primary bronchial epithelia, IFN-λ

Topic: cytokine – inflammation – lung – antiviral agents – disease outbreaks –  interferons – interleukin-8 – malaysia – rna, viral – signs and symptoms, respiratory – suidae – virus replication – infection – interleukin-6 – viruses – epithelial cells – airway device – nipah virus – nipah virus infections

Issue Section: Supplement Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Nipah virus; Cytokines; Immunopathology; Viral pathogenesis.

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