Augmented #Zika and #dengue neutralizing #antibodies are associated with #GBS (J Infect Dis., abstract)

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

Augmented Zika and dengue neutralizing antibodies are associated with Guillain-Barré syndrome 

Rebecca M Lynch, Grace Mantus, Liliana Encinales, Nelly Pacheco, Guangzhao Li, Alexandra Porras, Alejandro R Mendoza, Jin Peng, Monica Rengifo-Pardo, Magelda Montoya Cruz, Eva Harris, Jeff M Bethony, Gary L Simon, Aileen Y Chang

The Journal of Infectious Diseases, jiy466, https://doi.org/10.1093/infdis/jiy466

Published: 03 August 2018

 

Abstract

The role of neutralizing antibodies in Zika-induced Guillain-Barré syndrome (GBS) has not yet been investigated. We conducted a case-control study using sera from the 2016 Zika epidemic in Colombia to determine the neutralizing antibody activity against Zika virus (ZIKV) and dengue virus serotype 2 (DENV2). We observed increased neutralizing antibody titers against DENV2 in ZIKV-infected individuals compared to uninfected controls and higher titers to both ZIKV and DENV2 in ZIKV-infected patients diagnosed with GBS compared to non-GBS ZIKV infected controls. These data suggest that high neutralizing antibodies titers to DENV and to ZIKV are associated with GBS during ZIKV infection.

Guillain-Barré syndrome, neutralizing antibody, flavivirus, Zika, Dengue

Issue Section: Brief Report

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: Zika Virus; Dengue Fever; GBS; Serosurveys.

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#Immune responses to #MERS #coronavirus during the acute and convalescent phases of #human #infection (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2018 Jul 27. doi: 10.1093/cid/ciy595. [Epub ahead of print]

Immune responses to MERS coronavirus during the acute and convalescent phases of human infection.

Shin HS1, Kim Y1, Kim G1, Lee JY2, Jeong I2, Joh JS2, Kim H3, Chang E3, Sim SY3, Park JS4, Lim DG3.

Author information: 1 Center for Infectious Diseases, Department of Internal Medicine, National Medical Center, Seoul, Korea. 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Center, Seoul, Korea. 3 Center for Chronic Diseases, National Medical Center, Seoul, Korea. 4 Center for Infectious Diseases, Research Institute, National Medical Center, Seoul, Korea.

 

Abstract

BACKGROUND:

An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection.

METHODS:

We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells (PBMCs) with overlapping peptides spanning whole virus structural proteins.

RESULTS:

At the acute phase of infection, elevated levels of plasma pro-inflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS-CoV-reactive CD8+ T cells were also observed in patients with severe/moderate illness, while antibody and CD4+ T cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T cell subsets. These T cells belonged to the Th1 or Tc1 subtypes. While CD8+ T cells responded preferentially to the viral S protein than to E/M/N proteins especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins versus S protein at the convalescent phase.

CONCLUSIONS:

Our findings show an association between the early CD8+ T cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.

PMID: 30060038 DOI: 10.1093/cid/ciy595

Keywords: MERS-CoV; Immunopathology.

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#Human #Serum With High Neutralizing #Antibody Titers Against Both #Zika and #Dengue Virus Shows Delayed In Vitro #ADE of Dengue Virus Infection (Open Forum Infect Dis., abstract)

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

Open Forum Infect Dis. 2018 Jun 22;5(7):ofy151. doi: 10.1093/ofid/ofy151. eCollection 2018 Jul.

Human Serum With High Neutralizing Antibody Titers Against Both Zika and Dengue Virus Shows Delayed In Vitro Antibody-Dependent Enhancement of Dengue Virus Infection.

Valiant WG1, Lalani T2,3,4, Yun HC5, Kunz A6, Burgess TH2, Mattapallil JJ1.

Author information: 1 F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland. 2 Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University, Rockville, Maryland. 3 Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland. 4 Division of Infectious Diseases, Naval Medical Center, Portsmouth, Virginia. 5 San Antonio Military Medical Center, San Antonio, Texas. 6 Madigan Army Medical Center, Tacoma, Washington.

 

Abstract

Zika virus infection in a dengue virus-naïve subject was associated with the induction of high levels of cross-reactive binding antibodies. These responses were, however, largely non-neutralizing and displayed a capacity to enhance dengue infection in vitro at significantly low dilution (1:10). In contrast, a subject who had high levels of neutralizing antibodies against both dengue and Zika viruses enhanced infection at a dilution of 1:10 000. These results suggest that high levels of dengue cross-neutralizing antibodies could potentially prevent the enhancement of dengue infection in Zika virus-convalescent individuals.

KEYWORDS: Zika virus; antibody-dependent enhancement; cross- neutralization; dengue virus

PMID: 30019003 PMCID: PMC6041987 DOI: 10.1093/ofid/ofy151

Keywords: Zika Virus; Dengue Fever; ADE.

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T-Cell #Receptor Diversity and the Control of T-Cell Homeostasis Mark #Ebola Virus Disease #Survival in #Humans (J Infect Dis., abstract)

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

T-Cell Receptor Diversity and the Control of T-Cell Homeostasis Mark Ebola Virus Disease Survival in Humans

Emily Speranza, Paula Ruibal, Julia R Port, Feng Feng, Lia Burkhardt, Adam Grundhoff, Stephan Günther, Lisa Oestereich, Julian A Hiscox, John H Connor, César Muñoz-Fontela

The Journal of Infectious Diseases, jiy352, https://doi.org/10.1093/infdis/jiy352

Published: 06 July 2018

 

Abstract

Differences in T-cell phenotype, particularly the expression of markers of T-cell homeostasis, have been observed in fatal and nonfatal Ebola virus disease (EVD). However, the relationship between these markers with T-cell function and virus clearance during EVD is poorly understood. To gain biological insight into the role of T cells during EVD, combined transcriptomics and T-cell receptor sequencing was used to profile blood samples from fatal and nonfatal EVD patients from the recent West African EVD epidemic. Fatal EVD was characterized by strong T-cell activation and increased abundance of T-cell inhibitory molecules. However, the early T-cell response was oligoclonal and did not result in viral clearance. In contrast, survivors mounted highly diverse T-cell responses, maintained low levels of T-cell inhibitors, and cleared Ebola virus. Our findings highlight the importance of T-cell immunity in surviving EVD and strengthen the foundation for further research on targeting of the dendritic cell-T cell interface for postexposure immunotherapy.

Ebola virus, gene expression, T cells, T-cell receptor

Issue Section: Supplement Article

© The Author(s) 2018. 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: Ebola; Immunology.

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Prolonged #evolution of virus-specific memory T cell #immunity post severe #avian #influenza A (#H7N9) virus #infection (J Virol., abstract)

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

Prolonged evolution of virus-specific memory T cell immunity post severe avian influenza A (H7N9) virus infection

Min Zhao1,2, Junbo Chen3, Shuguang Tan1, Tao Dong4, Hui Jiang5, Jiandong Zheng5, Chuansong Quan6, Qiaohong Liao5, Hangjie Zhang6, Xiling Wang3, Qianli Wang3, Yuhai Bi1, Fengfeng Liu5, Luzhao Feng5, Peter W. Horby7,  Paul Klenerman8, George F. Gao1,2,6, William J. Liu6⇑ and Hongjie Yu3⇑

Author Affiliations: 1 Beijing Institutes of Life Science, Chinese Academy of Sciences, China; 2 CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; 3 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; 4 Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; 5 Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China; 6 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; 7 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 8 Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK

 

ABSTRACT

Since 2013, influenza A/H7N9 has emerged as the commonest avian influenza subtype causing human infection, and is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of forty-five H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5-4 months, 6-8 months and 12-15 months post-infection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to ICU and patients presenting with ARDS than that in patients with mild disease. Frequencies of virus-specific IFN-γ secreting T cells were lower in critically ill patients requiring ventilation than those in patients without ventilation within four months after infection. The percentages of H7N9-specific IFN-γ secreting T cells tended to increase over time in patients ≥60 years or critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8+ T cells expressing lung-homing marker CD49a were observed at 6-8 months after H7N9 infection compared to samples obtained at 1.5-4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients, and provide implications for T-cell directed immunization strategies.

 

IMPORTANCE

Avian influenza A H7N9 remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase over time in older and severely ill patients. Higher levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were detected at 6-8 months after infection. Our results indicated a long term impact of H7N9 infection on virus-specific memory T cells. These findings advance our understanding of the dynamics of virus-specific memory T cell immunity after H7N9 infection, relevant to the development of T cell based universal influenza vaccines.

 

FOOTNOTES

Correspondence and requests for materials should be addressed to H.Y. or W.J.L (email: cfetpyhj@vip.sina.com or liujun@ivdc.chinacdc.cn)

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Avian Influenza; H7N9; Human; Immunology.

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Comprehending a #Killer: The Akt/mTOR Signaling Pathways Are Temporally High-Jacked by the Highly Pathogenic 1918 #Influenza Virus (EBioMedicine, abstract)

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

EBioMedicine. 2018 Jun 1. pii: S2352-3964(18)30191-9. doi: 10.1016/j.ebiom.2018.05.027. [Epub ahead of print]

Comprehending a Killer: The Akt/mTOR Signaling Pathways Are Temporally High-Jacked by the Highly Pathogenic 1918 Influenza Virus.

Ranadheera C1, Coombs KM2, Kobasa D3.

Author information: 1 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0J6, Canada; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. 2 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0J6, Canada; Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, Manitoba R3E 3P4, Canada; Manitoba Institute of Child Health, John Buhler Research Centre, Room 513, 715 McDermot Avenue, Winnipeg, Manitoba R3E 3P4, Canada. Electronic address: kevin.coombs@umanitoba.ca. 3 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0J6, Canada; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. Electronic address: darwyn.kobasa@phac-aspc.gc.ca.

 

Abstract

Previous transcriptomic analyses suggested that the 1918 influenza A virus (IAV1918), one of the most devastating pandemic viruses of the 20th century, induces a dysfunctional cytokine storm and affects other innate immune response patterns. Because all viruses are obligate parasites that require host cells for replication, we globally assessed how IAV1918 induces host protein dysregulation. We performed quantitative mass spectrometry of IAV1918-infected cells to measure host protein dysregulation. Selected proteins were validated by immunoblotting and phosphorylation levels of members of the PI3K/AKT/mTOR pathway were assessed. Compared to mock-infected controls, >170 proteins in the IAV1918-infected cells were dysregulated. Proteins mapped to amino sugar metabolism, purine metabolism, steroid biosynthesis, transmembrane receptors, phosphatases and transcription regulation. Immunoblotting demonstrated that IAV1918 induced a slight up-regulation of the lamin B receptor whereas all other tested virus strains induced a significant down-regulation. IAV1918 also strongly induced Rab5b expression whereas all other tested viruses induced minor up-regulation or down-regulation. IAV1918 showed early reduced phosphorylation of PI3K/AKT/mTOR pathway members and was especially sensitive to rapamycin. These results suggest the 1918 strain requires mTORC1 activity in early replication events, and may explain the unique pathogenicity of this virus.

KEYWORDS: Bioinformatics; Host cell alterations; Liquid chromatography; Mass spectrometry; RNA virus; Virus infection

PMID: 29866590 DOI: 10.1016/j.ebiom.2018.05.027

Keywords: Pandemic Influenza; H1N1; Spanish Flu.

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#Galectin-3 enhances #avian #H5N1 #influenza A virus–induced #pulmonary #inflammation by promoting NLRP3 inflammasome activation (Am J Pathol., abstract)

[Source: American Journal of Pathology, full page:  (LINK). Abstract, edited.]

Galectin-3 enhances avian H5N1 influenza A virus–induced pulmonary inflammation by promoting NLRP3 inflammasome activation

Yu-Jung Chen, Sheng-Fan Wang, I-Chun Weng, Ming-Hsiang Hong, Tzu-Han Lo, Jia-Tsrong Jan, Li-Chung Hsu, Huan-Yuan Chen, Fu-Tong

DOI: http://dx.doi.org/10.1016/j.ajpath.2017.12.014

Published online: January 21, 2018 – Accepted: December 28, 2017 – Received in revised form: December 18, 2017 – Received:August 30, 2017

 

Abstract

Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a β-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here we describe galectin-3 up-regulation in mouse lung tissue following challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable to wild-type (WT) mice following infections. Compared to infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced interleukin-1 beta (IL-1β) levels in bronchoalveolar lavage fluid. Also, the bone marrow–derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains, and secreted less IL-1β compared to BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain–like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3-ASC complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1β production by macrophages via interaction with NLRP3.

Funding: Supported by Academia Sinica and Ministry of Science and Technology, Republic of China [MOST103-100 (H-Y.C.), MOST 106-0210-01-15-02 (F-T.L.) and MOST 106-2321-B-037-001 (S-F.W.)].

Disclosures: Anti–galectin-3 and anti–caspase-1 (p20) were gifts from Genentech.

© 2018 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.

Keywords: Avian Influenza; H5N1; Immunopathology.

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