#Mitochondria Redistribution in #Enterovirus A71 Infected Cells and Its Effect on Virus #Replication (Virol Sin., abstract)

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

Mitochondria Redistribution in Enterovirus A71 Infected Cells and Its Effect on Virus Replication

Authors: Yang Yang, Haolong Cong, Ning Du, Xiaodong Han, Lei Song, Wenliang Zhang,
Chunrui Li, Po Tien

Research Article / First Online: 08 May 2019

 

Abstract

Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD) and it also causes severe neurologic complications in infected children. The interactions between some viruses and the host mitochondria are crucial for virus replication and pathogenicity. In this study, it was observed that EV-A71 infection resulted in a perinuclear redistribution of the mitochondria. The mitochondria rearrangement was found to require the microtubule network, the dynein complex and a low cytosolic calcium concentration. Subsequently, the EV-A71 non-structural protein 2BC was identified as the viral protein capable of inducing mitochondria clustering. The protein was found localized on mitochondria and interacted with the mitochondrial Rho GTPase 1 (RHOT1) that is a key protein required for attachment between the mitochondria and the motor proteins, which are responsible for the control of mitochondria movement. Additionally, suppressing mitochondria clustering by treating cells with nocodazole, EHNA, thapsigargin or A23187 consistently inhibited EV-A71 replication, indicating that mitochondria recruitment played a crucial role in the EV-A71 life cycle. This study identified a novel function of the EV-A71 2BC protein and provided a potential model for the regulation of mitochondrial motility in EV-A71 infection.

Keywords: Enterovirus A71 (EV-A71) – Mitochondria – Microtubule network – Calcium concentration – Mitochondrial Rho GTPase 1 (RHOT1)

 

Electronic supplementary material

The online version of this article ( https://doi.org/10.1007/s12250-019-00120-5) contains supplementary material, which is available to authorized users.

Yang Yang and Haolong Cong have contributed equally to this study.
Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (Grants Nos. 81621091, 31370201). We are grateful to Prof. Paul Chu, Guest Professor of the Institute of Microbiology, Chinese Academy of Sciences (CAS), for his help during the preparation of the manuscript. We thank Xiaolan Zhang and Tong Zhao, Institute of Microbiology, CAS, for technical help with confocal microscopy and flow cytometry. We also thank Fulian Liao and Weihua Zhuang for their assistance with the experiments.

Author Contributions

YY, HC and PT designed the research. YY and HC performed the experiments. ND, XH, LS, WZ and CL provided experiment support. YY and HC wrote the manuscript. All authors have read and approved the final manuscript for submission.

 

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Enterovirus; EV-A71; Viral pathogenesis.

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#Outbreak of #aseptic #meningitis caused by #echovirus 30 in Kushiro, #Japan in 2017 (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 6 May 2019 / In Press, Accepted Manuscript

Outbreak of aseptic meningitis caused by echovirus 30 in Kushiro, Japan in 2017

Yuji Maruo a, Masanori Nakanishi a, Yasuto Suzuki a, Yosuke Kaneshi a, Yukayo Terashita a, Masashi Narugami a, Michi Takahashi a, Sho Kato a, Ryota Suzuki a, Akiko Goto b, Masahiro Miyoshi b, Hideki Nagano b, Takahisa Sugisawa c, Motohiko Okano b

{a} Department of Pediatrics, Kushiro Red Cross Hospital, 21-14, Shinei-cho, Kushiro 085-8512, Japan; {b} Hokkaido Institute of Public Health, North 19 West 12, Kita-ku, Sapporo 060-0819, Japan; {c} Kushiro Center of Public Health, 4-22, Shiroyama 2, Kushiro 085-0826, Japan

Received 14 January 2019, Revised 23 April 2019, Accepted 5 May 2019, Available online 6 May 2019. DOI: https://doi.org/10.1016/j.jcv.2019.05.001

 

Highlights

  • There was an outbreak of aseptic meningitis caused by E30 in Kushiro, Japan.
  • A neutrophil predominance was shown in CSF samples in many patients.
  • Phylogenetic analysis showed the same cluster.
  • Genotype of E30 was more closely related to strains in Europe than those in Japan.
  • Standard precautions are considered essential to prevent the spread of E30 infection.

 

Abstract

Background

Echovirus 30 (E30) is one of the most common causative agents for aseptic meningitis.

Objectives

In the autumn of 2017, there was an outbreak caused by E30 in Kushiro, Hokkaido, Japan. The aim of this study was to characterize this outbreak.

Study design

Fifty-nine patients were admitted to the Department of Pediatrics, Kushiro Red Cross Hospital (KRCH) with clinical diagnosis of aseptic meningitis. Among those, 36 patients were finally diagnosed as E30-associated aseptic meningitis by the detection of viral RNA using reverse transcription-polymerase chain reaction (RT-PCR) and/or the evidence of more than four-fold rise in neutralizing antibody (NA) titers in the convalescent phase relative to those in the acute phase. We investigated these 36 confirmed cases.

Results

The median age was 6 years (range: 6 months–14 years). The positive signs and symptoms were as follows: fever (100%), headache (94%), vomiting (92%), jolt accentuation (77%), neck stiffness (74%), Kernig sign (29%), and abdominal pain (28%). The median cerebrospinal fluid (CSF) white cell count, neutrophil count, and lymphocyte count were 222 /μL (range: 3–1,434 /μL), 144 /μL (range: 1–1,269 /μL), and 85 /μL (range: 2–354 /μL), respectively. Although the detected viral genes demonstrated same cluster, they were different from E30 strains observed in Japan between 2010 and 2014.

Conclusion

We mainly showed clinical and virological features of the E30-associated aseptic meningitis outbreak that occurred in Kushiro. To prevent further spread of E30 infection, continuous surveillance of enterovirus (EV) circulation and standard precautions are considered essential.

Abbreviations: E30 Echovirus 30 – EV enterovirus – KRCH Kushiro Red Cross Hospital –
RT-PCR reverse transcription-polymerase chain reaction – NA neutralizing antibody – CSF cerebrospinal fluid – CODEHOP consensus-degenerate hybrid oligonucleotide primer – VP viral protein – NT neutralization test – IgG immunoglobulin G – CRP C-reactive protein –

Keywords: aseptic meningitis – echovirus 30 – enterovirus – outbreak – children

© 2019 Elsevier B.V. All rights reserved.

Keywords: Enterovirus; Echovirus 30; Meningitis; Japan.

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#Picornavirus #etiology of acute #infections among hospitalized #infants (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 25 April 2019 / In Press, Accepted Manuscript

Picornavirus etiology of acute infections among hospitalized infants

Glen R.Abedi a, Kevin Messacar b, William Luong c, W. Allan Nix a, Shannon Rogers a, Krista Queen a, Suxiang Tong a, M. Steven Oberste a, James Watt c, Gretchen Rothrock c, Samuel Dominguez b, Susan I. Gerber a, John T. Watson a

{a} Division of Viral Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Ga, United States; {b}
Colorado Emerging Infections Program, Denver, Colo., United States; {c} California Emerging Infections Program, Richmond, Calif., United States

Received 4 December 2018, Revised 17 April 2019, Accepted 23 April 2019, Available online 25 April 2019. DOI: https://doi.org/10.1016/j.jcv.2019.04.005

 

Highlights

  • Enteroviruses (EV) and parechoviruses (PeV) are ubiquitous viruses that cause a range of illness, including acute illness in children aged <1 year.
  • Of 319 patients aged <1 year, CSF specimens from 13 (4.1%) were positive for EV and from 11 (3.4%) for PeV.
  • Sequencing revealed a variety of EV types and the predominance of PeV-A3 among the PeV-positive case-patients.
  • Clinicians should consider EV and PeV infections in infants presenting with febrile illness.

 

Abstract

Background

Enteroviruses (EV) and parechoviruses (PeV) are ubiquitous viruses that cause a range of illness, including acute illness in children aged <1 year.

Objectives

We describe EV and PeV infections among children from 2 US study sites aged <1 year and hospitalized with acute infections. For EV- and PeV-negative case-patients, we explored other viral etiologies.

Methods

Participants were aged <1 year, hospitalized during 2016, and had cerebrospinal fluid (CSF) collected for routine diagnostic testing. Demographic and clinical data were abstracted from medical charts, and residual specimens were sent to CDC for confirmatory testing and typing.

Results

Of 472 eligible case-patients, CSF specimen was available for 319 (67.6%). Among those, 13 (4.1%) were positive for EV and 11 (3.4%) for PeV. Most case-patients (86.8%, n = 277) were aged <2 months, as were all EV- or PeV-positive case-patients. None of the positive case-patients had underlying conditions, and the chief complaint for 91.7% (n = 22) was fever. Twelve positive case-patients were admitted to intensive care (ICU) and had brief hospital stays (median 2 days). Sequencing revealed a variety of EV types and the predominance of PeV-A3 among the PeV-positive case-patients.

Conclusions

A range of EVs and PeVs were associated with acute febrile illnesses leading to hospitalization in children aged <2 months. Approximately half of EV and PeV case-patients were admitted to ICU, but length of hospital stay was brief and illnesses were generally self-limiting. Clinicians should consider EV and PeV infections in infants presenting with febrile illness.

Keywords: enterovirus – parechovirus – infants – fever – sepsis – encephalitis – meningitis

{☆} The conclusions, findings, and opinions expressed by the authors do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Centers for Disease Control and Prevention, or the authors’ affiliated institutions.

© 2019 Published by Elsevier B.V.

Keywords: Enterovirus; Picornavirus; Parechovirus; Encephalitis; Meningitis; Sepsis; Pediatrics.

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#Genetic #landscape and macro-evolution of co-circulating #Coxsackieviruses A and #VDPV in the #DRC, 2008-2013 (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013

Serge Alain Sadeuh-Mba , Hugo Kavunga-Membo, Marie-Line Joffret, Riziki Yogolelo, Marie Claire Endegue-Zanga, Maël Bessaud, Richard Njouom, Jean-Jacques Muyembe-Tamfu, Francis Delpeyroux

Published: April 19, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007335 / This is an uncorrected proof.

 

Abstract

Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5’-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5’UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpolregion. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.

 

Author summary

The strategy of the Global Polio Eradication Initiative is based on the surveillance of patients suffering from Acute Flaccid Paralysis (AFP) and mass vaccination with live-attenuated vaccine strains of polioviruses (PVs) in endemic areas. However, vaccine strains of PVs can circulate and replicate for a long time when the vaccine coverage of the population is low. Such prolonged circulation and replication of vaccine strains of PVs can result to the emergence of circulating vaccine-derived polioviruses [cVDPVs] that are as virulent as wild PVs. In this study, we performed the molecular characterization of a large collection of 377 virus isolates recovered from paralyzed patients between 2008 and 2012 in DR Congo and healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. We found that the genetic diversity of enteroviruses of the species Enterovirus C is more important than previously reported. Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences of the 2C ATPase and/or 3D polymerase coding genes acquired from co-circulating Coxsackieviruses A13, A17 and A20. Coxsackieviruses A20 strains were identified for the first time as major partners of genetic recombination with co-circulating live-attenuated polio vaccine strains.

Our findings highlight the need to reinforce and maintain high quality surveillance of PVs and efficient immunization activities in order to ensure early detection and control of emerging cVDPVs in all settings where high frequency and diversity of Coxsackieviruses A13, A17 and A20 have been documented.

____

Citation: Sadeuh-Mba SA, Kavunga-Membo H, Joffret M-L, Yogolelo R, Endegue-Zanga MC, Bessaud M, et al. (2019) Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013. PLoS Negl Trop Dis 13(4): e0007335. https://doi.org/10.1371/journal.pntd.0007335

Editor: Maia A. Rabaa, Oxford University Clinical Research Unit, VIET NAM

Received: January 10, 2019; Accepted: March 27, 2019; Published: April 19, 2019

Copyright: © 2019 Sadeuh-Mba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All 579 newly determined genomic sequences are available from the GenBank database (https://www.ncbi.nlm.nih.gov/genbank/) using the accession numbers MK310554 to MK311132.

Funding: This work was carried out with the funding from the “Polio Research Committee” of the World Health Organization (http://polioeradication.org/tools-and-library/research-innovation/polio-research-committee/) through the grant WHO 2012/262176-0 awarded to SASM, JJMT and FD for the collaborative project HOPOL1206310. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Enterovirus; Coxsackievirus A13, A17, A20; Recombination; Vaccine-derived poliovirus; DRC.

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Acute Flaccid #Myelitis: Something Old and Something New (mBio, abstract)

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

Acute Flaccid Myelitis: Something Old and Something New

David M. Morens, Gregory K. Folkers, Anthony S. Fauci

Arturo Casadevall, Editor

DOI: 10.1128/mBio.00521-19

 

ABSTRACT

Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity. This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence.

Keywords: Enterovirus; EV-D68; AFM.

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Immunogenicity and safety of an inactivated #EV71 #vaccine administered simultaneously with recombinant #hepatitis B vaccine and group A #meningococcal polysaccharide vaccine… (J Infect Dis., abstract)

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

Immunogenicity and safety of an inactivated enterovirus 71 vaccine administered simultaneously with recombinant hepatitis B vaccine and group A meningococcal polysaccharide vaccine:  a phase IV, open-label, single-center, randomized, non-inferiority trial

Zewu Zhang, MS, Zhenglun Liang, PhD, Ji Zeng, MS, Jikai Zhang, MS, Peng He, MS, Jiali Su, MS, Yaoming Zeng, BS, Renfeng Fan, MS, Dan Zhao, BS, Wenjun Ma, MS, Gang Zeng, PhD, Qiaoli Zhang, MS, Huizhen Zheng, BS

The Journal of Infectious Diseases, jiz129, https://doi.org/10.1093/infdis/jiz129

Published: 19 March 2019

 

Abstract

Background

This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of the combined EV71 vaccine with recombinant hepatitis B vaccine (HepB) and group A meningococcal polysaccharide vaccine (MenA) is not inferior to separate administration of each vaccine.

Methods

The study was designed as a randomized, open-label, and non-inferiority trial, and was registered at ClinicalTrials.gov (NCT03274102). A total of 775 healthy infants aged 6 months were randomized 1:1:1 to simultaneous administration (SI) or separate administration (SE1:EV71 and SE2: HepB followed by MenA).

Results

According to per protocol set, antibody response against EV71, hepatitis B virus and group A meningococcal polysaccharide was similar regardless of administration schedule. With the non-inferiority margin set at 10%, the seroconversion of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) was not inferior to that of SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72]). The occurrences of adverse reactions of each vaccination regimen were comparable (60.62% vs 52.33% and 56.98%, P = 0.16).

Conclusions

Simultaneous administration of combined EV71 vaccine with HepB and MenA shows non inferiority in immunogenicity and safety compared with separate administration.

Clinical Trial Registration NCT03274102

simultaneous administration, EV71 vaccine, phase-IV trial

Issue Section: Major Article

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© 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: Enterovirus; EV-71; Vaccines.

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#Enterovirus A71 Phenotypes Causing #HFMD, #Vietnam (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 4—April 2019 / Dispatch

Enterovirus A71 Phenotypes Causing Hand, Foot and Mouth Disease, Vietnam

Hoang Minh Tu Van  , Nguyen To Anh, Nguyen Thi Thu Hong, Le Nguyen Truc Nhu, Lam Anh Nguyet, Tran Tan Thanh, Nguyen Thi Han Ny, Vu Thi Ty Hang, Truong Huu Khanh, Ho Lu Viet, Do Chau Viet, Ha Manh Tuan, Nguyen Thanh Hung, Du Tuan Quy, Do Quang Ha, Phan Tu Qui, Le Nguyen Thanh Nhan, Guy Thwaites, Nguyen Van Vinh Chau, Louise Thwaites, H. Rogier van Doorn, and Le Van Tan

Author affiliations: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (H.M.T. Van, N.T. Anh, N.T.T. Hong, L.N.T. Nhu, L.A. Nguyet, T.T. Thanh, N.T.H. Ny, V.T.T. Hang, D.Q. Ha, G. Thwaites, L. Thwaites, H.R. van Doorn, L.V. Tan); Children’s Hospital 2, Ho Chi Minh City (H.M.T. Van, H.L. Viet, D.C. Viet, H.M. Tuan); Children’s Hospital 1, Ho Chi Minh City (T.H. Khanh, N.T. Hung, D.T. Quy, L.N.T. Nhan); University of Oxford, Oxford, UK (P.T. Qui, G. Thwaites, L. Thwaites, H.R. van Doorn); Hospital for Tropical Diseases, Ho Chi Minh City (N.V.V. Chau)

 

Abstract

We investigated enterovirus A71–associated hand, foot and mouth disease in Vietnam and found that, after replacing subgenogroup C4 in 2013, B5 remained the leading cause of this disease. In contrast with previous observations, this switch did not result in an explosive outbreak, and B5 evolution was driven by negative selection.

Keywords: Enterovirus; EV-A71; HFMD; Vietnam.

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