#Complement mediated #neutralization of a potent #neurotropic #human #pathogen, #Chandipura virus, is dependent on C1q (J Virol., abstract)

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

Complement mediated neutralization of a potent neurotropic human pathogen, Chandipura virus, is dependent on C1q.

Umerali Kunnakkadan, Joydeep Nag, Nisha Asok Kumar, Reshma Koolaparambil Mukesh, Sreenath Muraleedharan Suma, John Bernet Johnson

DOI: 10.1128/JVI.00994-19



Among the innate immune sentinels, the complement system is a formidable first line of defense against pathogens including viruses. Chandipura virus (CHPV), a neurotropic vesiculovirus of the family Rhabdoviridae is a deadly human pathogen known to cause fatal encephalitis especially among children. The nature of interaction and the effect of human complement on CHPV are unknown. Here, we report that CHPV is a potent activator of complement and thus is highly sensitive to complement proteins in normal human serum (NHS). Utilizing a panel of specific complement component depleted/reconstituted human serum we have demonstrated that CHPV neutralization is C3, C4 and C1q dependent and independent of factor B suggesting the importance of the classical pathway in limiting CHPV. Employing a range of biochemical approaches we could show a) direct association of C1q to CHPV b) deposition of complement proteins C3b, C4b and C1q on CHPV and c) virus aggregation. Depletion of C8, an important component of the pore forming complex of complement had no effect on CHPV further supporting the finding that aggregation and not virolysis is the mechanism of virus neutralization. With no approved vaccines or treatment modalities in place against CHPV, insights into such interactions can be exploited to develop potent vaccines or therapeutics targeting CHPV.



Chandipura virus is a clinically important human pathogen of the Indian subcontinent. The rapidity in death associated with CHPV infection in addition to the absence of an effective vaccine or therapeutics results in poor clinical prognosis. The biology of the virus and its interaction with the host immune system including the complement system is understudied. Our investigation reveals the susceptibility of CHPV to fluid phase complement and also dissects the pathway involved and the mechanism of virus neutralization. Direct binding of C1q, an important upstream component of the classical pathway of complement to CHPV and the strong dependency on C1q for virus neutralization highlights the significance of identifying such interactions to better understand CHPV pathogenesis and devise strategies to target this deadly pathogen.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Rhabdovirus; Vesciculavirus; Chandipura virus; Viral pathogenesis.



Lethal #Encephalitis in #Seals with #JEV #Infection, #China, 2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 8—August 2019 / Dispatch

Lethal Encephalitis in Seals with Japanese Encephalitis Virus Infection, China, 2017

Xiangdong Li1, Mingming Qiao1, Xiaoyu Deng, Xi Chen, Shengyong Sun, Qian Zhang, Wenjie Zhang, Feifei Tan, Zhe Sun, Xizhao Chen, Ming Sun2  , and Kegong Tian2

Author affiliations: National Research Center for Veterinary Medicine, Luoyang, China (X. Li, F. Tan, Z. Sun, K. Tian); Beijing Anheal Laboratories Co. Ltd, Beijing, China (M. Qiao, X. Deng, Xi Chen, S. Sun, Q. Zhang, W. Zhang, Xizhao Chen, M. Sun); Henan Agricultural University, Zhengzhou, China (K. Tian)



We isolated Japanese encephalitis virus (JEV) from brain samples of 2 seals with lethal encephalitis at Weihai Aquarium, Weihai, China, in 2017. We confirmed our findings by immunohistochemical staining and electron microscopy. Phylogenetic analysis showed this virus was genotype I. Our findings suggest that JEV might disseminate though infected zoo animals.

Keywords: Japanese Encephalitis Virus; Seals; Wildlife; Encephalitis.


A rare case of #influenza A (#H3N2)-associated #encephalitis with #seizure (Am J Emerg Med., abstract)

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

Am J Emerg Med. 2019 Jun 16. pii: S0735-6757(19)30406-1. doi: 10.1016/j.ajem.2019.06.027. [Epub ahead of print]

A rare case of influenza A (H3N2)-associated encephalitis with seizure.

Yuan HT1, Ho TH2, Lee JT2, Chen PC3, Wang CW4, Yang FC5.

Author information: 1 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan; Division of Neurology, Department of Internal Medicine, Tri-Service General Hospital Sungsan Branch, National Defense Medical Center, No.131, Jiankang Road, Songshan 104, Taipei, Taiwan. 2 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. 3 Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. 4 Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. 5 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. Electronic address: fuji-yang@yahoo.com.tw.



Influenza-associated acute encephalopathy (IAE) is more prevalent in children than in adults and often results in neurological sequelae or even death. Diagnosis of IAE is difficult as clinical presentation varies significantly and the influenza virus is rarely detected in cerebrospinal fluid. Moreover, seizures in adults due to influenza infection are rare. Herein, we describe the case of an adult presenting with both acute encephalitis and seizures. A 38-year-old female was admitted to the emergency department with acute respiratory symptoms and fever, followed by quick progression to stupor within 24 h. A rapid antigen test was influenza A-positive, and polymerase chain reaction of nasal secretions confirmed the H3N2 subtype. Brain magnetic resonance imaging showed bilateral water restriction lesions at the thalamus and the cerebellum and an electroencephalogram showed frequent episodic generalized sharp-and-slow waves over the bilateral frontal region. Based on the neuroimaging and laboratory findings, we diagnosed the patient with adult influenza A (H3N2)-related encephalitis complicated by seizure. Treatment with oseltamivir and anticonvulsants led to complete neurologic recovery by day 14. This report describes two unusual neurological manifestations of influenza A, i.e., encephalitis and seizures, in an adult. We emphasize that, in adults presenting with acute viral encephalitis, clinicians should consider influenza infection as part of the differential diagnosis, and that typical neuroimaging in conjunction with laboratory detection of influenza virus and/or intrathecal antibody production suggestive of IAE, may help establish an accurate diagnosis.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Adult; H3N2; Influenza A; Influenza associated encephalitis; Influenza associated seizures in adults; Magnetic resonance imaging

PMID: 31230923 DOI: 10.1016/j.ajem.2019.06.027

Keywords: Seasonal Influenza; H3N2; Encephalitis.


Central and peripheral #nervous system involvement in #Zika virus #infection in a #child (J Neurovirol., abstract)

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

J Neurovirol. 2019 Jun 20. doi: 10.1007/s13365-019-00770-x. [Epub ahead of print]

Central and peripheral nervous system involvement in Zika virus infection in a child.

Marinho PES1, Alvarenga PPM2,3, Lima MT1, de Souza Andrade A1, Candiani TMS2, Crispim APC1, Gasparini MCS1, Castro FS2, de Sousa AZA2, Viegas ECC2, de Oliveira DB4, Christo PP5, Kroon EG6.

Author information: 1 Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627 Caixa, Postal 486, Belo Horizonte, MG, 31270-901, Brazil. 2 Hospital Infantil João Paulo II, FHEMIG, Belo Horizonte, Minas Gerais, Brazil. 3 Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 4 Faculdade de Medicina de Diamantina, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Teófilo Otoni, Minas Gerais, Brazil. 5 Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil. 6 Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627 Caixa, Postal 486, Belo Horizonte, MG, 31270-901, Brazil. kroone@icb.ufmg.br.



A 7-year-old boy that presented an encephalomyeloradiculitis and no classic symptoms of arboviruses. Zika virus (ZIKV) was confirmed by molecular analyses of cerebrospinal fluid and 1 year later by plaque reduction neutralization test. This case demonstrates that ZIKV can be associated with diffuse nervous system infection in children.

KEYWORDS: Central nervous system; Children; Peripheral nervous system; Zika virus

PMID: 31222674 DOI: 10.1007/s13365-019-00770-x

Keywords: Zika Virus; Encephalitis; Neuroinvasion; Pediatrics.


Contemporary circulating #EVD68 strains infect and undergo retrograde #axonal transport in #spinal motor #neurons independent of sialic acid (J Virol., abstract)

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

Contemporary circulating enterovirus D68 strains infect and undergo retrograde axonal transport in spinal motor neurons independent of sialic acid

Alison M. Hixon, Penny Clarke, Kenneth L. Tyler

DOI: 10.1128/JVI.00578-19



Enterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human iPSC motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons.



Enterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigate the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: EV-D68; Encephalitis; AFM; Viral pathogenesis.


#CFR and #Risk factors for #Nipah Virus #Encephalitis: a systematic review and meta-analysis (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 21 May 2019 / In Press, Accepted Manuscript

Case fatality rate and Risk factors for Nipah Virus Encephalitis: a systematic review and meta-analysis

Sebastien Kenmoe a, Maurice Demanou a, Jean Joel Bigna b, Cyprien Nde Kengne c, Abdou Fatawou Modiyinji a,d, Fredy Brice N. Simo a,e, Sara Eyangoh f, Serge  Alain Sadeuh-Mba a, Richard Njouom a

{a} Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274 Yaoundé, Cameroon; {b} Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Yaoundé, Cameroon; {c} National AIDS Control Committee, Cameroon; {d} Department of Animals Biology and Physiology, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon; {e} Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroun; {f} Department of Mycobacteriology, Centre Pasteur of Cameroon, Yaoundé, Cameroon

Received 12 March 2019, Revised 28 April 2019, Accepted 17 May 2019, Available online 21 May 2019. DOI: https://doi.org/10.1016/j.jcv.2019.05.009



  • A substantial number of deaths are registered among patients with Nipah virus encephalitis.
  • Our meta-analysis shows that exposure to pigs, exposure to date palm sap, tree climbing and travel outside his sub-district are associated with an increased risk of NiV infection.
  • The combined probability of fruit consumption was higher in healthy controls compared to NiV infected cases.




A wide range of Nipah virus (NiV) encephalitis case fatality rates (CFR) have been reported. Data on the involvement of several potential risk factors in Nipah virus transmission remain controversial. We performed a systematic review and meta-analysis to estimate the pooled CFR of NiV encephalitis and to assess the risk factors for NiV infection.


Articles published up to the 27th of November 2018 in MedLine, Embase and Web of knowledge databases were considered for this study. We included cross-sectional, cohort, and case-control studies that have reported NiV CFR and/or risk factors. Data were pooled with random-effects model. This review was registered in the PROSPERO, CRD42018116242.


This global review included 22 citations (25 studies) including 2156, 1682, and 474 suspected, probable, and confirmed cases of NiV encephalitis, respectively. We determined a pooled CFR for NiV encephalitis at 61.0% (95% CI, 45.7-75.4; I² = 96.8%). Climbing trees (OR = 1.4; 95% CI; 1.0 to 1.9), male gender (OR = 1.5; 95% CI; 1.1 to 2.0), travel outside their own sub-district (OR = 2.0; 95% CI; 1.4 to 2.9), and exposure to date palm sap (DPS) (OR = 5.7; 95% CI; 3.8 to 8.6) or pigs (OR = 7.6; 95% CI; 1.2 to 45.4) were significantly associated with NiV infection.


Findings from this study suggest that NiV Encephalitis is associated with a high CFR and that male gender, travel outside their sub-district, climbing trees, and exposure to pigs and DPS are associated with an increased risk of NiV encephalitis.

Keywords: Case fatality rate – Risk factors – Nipah virus – Encephalitis

© 2019 Published by Elsevier B.V.

Keywords: Nipah virus; Encephalitis.


#Bacteroides fragilis #polysaccharide A induces IL-10 secreting B and T cells that prevent #viral #encephalitis (Nat Commun., abstract)

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

Article | OPEN | Published: 14 May 2019

Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis

Chandran Ramakrishna, Maciej Kujawski, Hiutung Chu, Lin Li, Sarkis K. Mazmanian & Edouard M. Cantin

Nature Communications, volume 10, Article number: 2153 (2019)



The gut commensal Bacteroides fragilis or its capsular polysaccharide A (PSA) can prevent various peripheral and CNS sterile inflammatory disorders. Fatal herpes simplex encephalitis (HSE) results from immune pathology caused by uncontrolled invasion of the brainstem by inflammatory monocytes and neutrophils. Here we assess the immunomodulatory potential of PSA in HSE by infecting PSA or PBS treated 129S6 mice with HSV1, followed by delayed Acyclovir (ACV) treatment as often occurs in the clinical setting. Only PSA-treated mice survived, with dramatically reduced brainstem inflammation and altered cytokine and chemokine profiles. Importantly, PSA binding by B cells is essential for induction of regulatory CD4+ and CD8+ T cells secreting IL-10 to control innate inflammatory responses, consistent with the lack of PSA mediated protection in Rag−/−, B cell- and IL-10-deficient mice. Our data reveal the translational potential of PSA as an immunomodulatory symbiosis factor to orchestrate robust protective anti-inflammatory responses during viral infections.

Keywords: Bacteroides fragilis; Immunomodulation; Encephalitis.