#Vector #Competence: What Has #Zika Virus Taught Us? (Viruses, abstract)

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

Viruses. 2019 Sep 17;11(9). pii: E867. doi: 10.3390/v11090867.

Vector Competence: What Has Zika Virus Taught Us?

Azar SR1,2,3, Weaver SC4,5,6.

Author information: 1 Department of Microbiology and Immunology, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA. srazar@utmb.edu. 2 Institute for Translational Sciences, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA. srazar@utmb.edu. 3 Institute for Human Infections and Immunity, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA. srazar@utmb.edu. 4 Department of Microbiology and Immunology, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA. sweaver@utmb.edu. 5 Institute for Translational Sciences, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA. sweaver@utmb.edu. 6 Institute for Human Infections and Immunity, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA. sweaver@utmb.edu.

 

Abstract

The unprecedented outbreak of Zika virus (ZIKV) infection in the Americas from 2015 to 2017 prompted the publication of a large body of vector competence data in a relatively short period of time. Although differences in vector competence as a result of disparities in mosquito populations and viral strains are to be expected, the limited competence of many populations of the urban mosquito vector, Aedes aegypti, from the Americas (when its susceptibility is viewed relative to other circulating/reemerging mosquito-borne viruses such as dengue (DENV), yellow fever (YFV), and chikungunya viruses (CHIKV)) has proven a paradox for the field. This has been further complicated by the lack of standardization in the methodologies utilized in laboratory vector competence experiments, precluding meta-analyses of this large data set. As the calls for the standardization of such studies continue to grow in number, it is critical to examine the elements of vector competence experimental design. Herein, we review the various techniques and considerations intrinsic to vector competence studies, with respect to contemporary findings for ZIKV, as well as historical findings for other arboviruses, and discuss potential avenues of standardization going forward.

KEYWORDS: Aedes aegypti; Flaviviruses; Zika virus; arbovirus; mosquitoes; vector competence

PMID: 31533267 DOI: 10.3390/v11090867

Keywords: Mosquitoes; Aedes aegypti; Flavivirus; Zika Virus.

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The #Atlastin ER-shaping #proteins facilitate #Zika virus #replication (J Virol., abstract)

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

The Atlastin ER-shaping proteins facilitate Zika virus replication

Blandine Monel, Maaran Michael Rajah, Mohamed-Lamine Hafirassou, Samy Sid-Ahmed, Julien Burlaud-Gaillard, Peng-Peng Zhu, Quentin Nevers, Julian Buchrieser, Françoise Porrot, Cécile Meunier, Sonia Amraoui, Maxime Chazal, Audrey Salles, Nolwenn Jouvenet, Philippe Roingeard, Craig Blackstone, Ali Amara, Olivier Schwartz

DOI: 10.1128/JVI.01047-19

 

ABSTRACT

The Endoplasmic Reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by “implosive” cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (ATL1/2/3) are dynamin-related GTPases that control the structure and the dynamics of the ER membrane. We show here that ZIKV replication is significantly decreased in the absence of ATL. The appearance of infected cells is delayed, the levels of intracellular viral proteins and released virus are reduced, and the cytopathic effects are strongly impaired. We further show that ATL3 is recruited to viral replication sites, and interacts with non-structural viral proteins NS2A and NS2B3. Thus, proteins that shape and maintain the ER tubular network ensure efficient ZIKV replication.

 

IMPORTANCE

Zika virus (ZIKV) is an emerging virus associated with Guillain-Barré syndrome, and fetal microcephaly as well as other neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We found that ER-shaping Atlastin proteins (ATL1/2/3), which induce ER membrane fusion, facilitate ZIKV replication. We show that ATL3 is recruited to the viral replication site and co-localize with the viral proteins NS2A and NS2B3. The results provide insights into host factors used by ZIKV to enhance its replication.

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

Keywords: Zika Virus.

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High #correlation between #Zika virus NS1 #antibodies and neutralizing antibodies in selected #serum samples from normal healthy #Thais (Sci Rep., abstract)

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

High correlation between Zika virus NS1 antibodies and neutralizing antibodies in selected serum samples from normal healthy Thais

Wannapa Sornjai, Suwipa Ramphan, Nitwara Wikan, Prasert Auewarakul & Duncan R. Smith

Scientific Reports, volume 9, Article number: 13498 (2019)

 

Abstract

Despite the widespread presence of the mosquito transmitted Zika virus (ZIKV) over much of Southeast Asia, the number of reported cases remains low. One possibility is that residents in Southeast Asia are immunologically protected, although the nature of any such protection remains unclear. This study sought to investigate the presence of antibodies directed to ZIKV NS1 protein in a selected sub-set of samples from a well characterized cohort of serum samples from normal, healthy Thais that had been previously characterized for the presence of neutralizing antibodies to ZIKV, DENV 1-4, and JEV. Because of similarities in molecular weight between the flavivirus E and NS1 proteins, an immunoblot system was established in which the NS1 antigen was not denatured, allowing detection of the dimer form of NS1, distinctly clear from the migration position of the E and NS1 monomer proteins. The results showed that antibodies to ZIKV NS1 protein were only detected in samples with ZIKV neutralizing antibodies (27/30 samples), and no sample (0/30) with a ZIKV plaque reduction neutralization test (PRNT)90 < 20 showed evidence of anti-ZIKV NS1 antibodies. The high correlation between the presence of ZIKV NS1 antibodies and ZIKV PRNT suggests that immunological protection against ZIKV infection in Thailand arises from prior exposure to ZIKV, and not through cross neutralization.

Keywords: Zika Virus; Serology; Thailand.

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Anti- #ganglioside #antibodies in patients with #Zika virus #infection-associated #GBS in #Brazil (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Anti-ganglioside antibodies in patients with Zika virus infection-associated Guillain-Barré Syndrome in Brazil

Juan Rivera-Correa, Isadora Cristina de Siqueira, Sabrina Mota, Mateus Santana do Rosário, Pedro Antônio Pereira de Jesus, Luiz Carlos Junior Alcantara, Joel D. Ernst, Ana Rodriguez

Published: September 17, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007695 / This is an uncorrected proof.

 

Abstract

Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients.

 

Author summary

Zika virus infection can trigger the development of Guillain Barré syndrome (GBS), a neurological autoimmune disorder mediated by antibodies recognizing gangliosides in nerve membranes. Mechanisms such as molecular mimicry have been identified as a cause for GBS development in certain infections, such as Campylobacter jejuni, but the broad self reactivity observed during GBS suggests a role for alternative mechanisms. Our finding that Zika patients with GBS present higher levels of anti-ganglioside antibodies compared to uncomplicated Zika patients in Brazil points to these auto-antibodies as a trigger for GBS in these patients. These findings further support infection-induced autoantibodies as a factor contributing to GBS development, adding novel mechanisms for GBS development beyond molecular mimicry.

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Citation: Rivera-Correa J, de Siqueira IC, Mota S, do Rosário MS, Pereira de Jesus PA, Alcantara LCJ, et al. (2019) Anti-ganglioside antibodies in patients with Zika virus infection-associated Guillain-Barré Syndrome in Brazil. PLoS Negl Trop Dis 13(9): e0007695. https://doi.org/10.1371/journal.pntd.0007695

Editor: Rebecca C. Christofferson, Louisiana State University, UNITED STATES

Received: March 18, 2019; Accepted: August 7, 2019; Published: September 17, 2019

Copyright: © 2019 Rivera-Correa 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 relevant data are within the manuscript and its Supporting Information files

Funding: AR and JRC received funding for this project from New York University School of Medicine Internal Funds. The funders 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: Zika Virus; Immunopathology; GBS; Neurology; Brazil.

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Role of #Zika Virus #Envelope Protein Domain III as a Target of #Human Neutralizing #Antibodies (mBio, abstract)

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

Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies

Emily N. Gallichotte, Ellen F. Young, Thomas J. Baric, Boyd L. Yount, Stefan W. Metz, Matthew C. Begley, Aravinda M. de Silva, Ralph S. Baric

J. S. Malik Peiris, Editor

DOI: 10.1128/mBio.01485-19

 

ABSTRACT

Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIII-targeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines.

 

IMPORTANCE

Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIII-specific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines.

Keywords: Zika Virus.

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#Azithromycin Protects against #Zika virus #Infection by Upregulating virus-induced Type I and III #Interferon Responses (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Azithromycin Protects against Zika virus Infection by Upregulating virus-induced Type I and III Interferon Responses

Chunfeng Li, Shulong Zu, Yong-Qiang Deng, Dapei Li, Kislay Parvatiyar, Natalie Quanquin, Jingzhe Shang, Nina Sun, Jiaqi Su, Zhenyang Liu, Min Wang, Saba R. Aliyari, Xiao-Feng Li, Aiping Wu, Feng Ma, Yi Shi, Karin Nielsevn-Saines, Jae U. Jung, Frank Xiao-Feng Qin, Cheng-Feng Qin, Genhong Cheng

DOI: 10.1128/AAC.00394-19

 

ABSTRACT

Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. Besides that, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes (ISGs) in response to ZIKV infection. In particular, we found that AZM upregulates the expression of MDA5 and RIG-I, pathogen recognition receptors (PRRs) induced by ZIKV infection, and increases the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulates phosphorylation of TBK1, without inducing phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and prevent ZIKV associated devastating clinical outcomes, such as congenital microcephaly.

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

Keywords: Antivirals; Antibiotics; Azithromycin; Zika Virus.

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#Geographical #trends of #chikungunya and #Zika in the #Colombian #Amazonian #gateway department, Caqueta, 2015-2018 – Implications for #publichealth and #travel medicine (Travel Med Infect Dis., abstract)

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

Travel Med Infect Dis. 2019 Sep 12:101481. doi: 10.1016/j.tmaid.2019.101481. [Epub ahead of print]

Geographical trends of chikungunya and Zika in the Colombian Amazonian gateway department, Caqueta, 2015-2018 – Implications for public health and travel medicine.

Bonilla-Aldana DK1, Bonilla-Aldana JL2, García-Bustos JJ3, Lozada CO4, Rodríguez-Morales AJ5.

Author information: 1 School of Veterinary Medicine and Zootechnics, Fundación Universitaria Autónoma de las Américas, Sede Pereira, Pereira, Risaralda, Colombia; Semillero de Zoonosis, Grupo de Investigación BIOECOS, Fundación Universitaria Autónoma de las Américas, Sede Pereira, Pereira, Risaralda, Colombia; Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia; Committee on Tropical Medicine, Zoonoses and Travel Medicine, Asociación Colombiana de Infectología (ACIN), Bogotá, Colombia. 2 Grupo de Investigación en Ciencias Animales Macagual, Universidad de La Amazonia, Florencia, Caquetá, 180002, Colombia. 3 Grupo de Investigación en Ciencias Animales Macagual, Universidad de La Amazonia, Florencia, Caquetá, 180002, Colombia; Grupo de Investigación en Patología e Inmunología – Doctorado en Medicina Tropical, Universidad del Magdalena, Santa Marta, Magdalena, 470004, Colombia. 4 Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia; Regional Information System, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia. 5 Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia; Committee on Tropical Medicine, Zoonoses and Travel Medicine, Asociación Colombiana de Infectología (ACIN), Bogotá, Colombia; Medical School, Faculty of Health Sciences, UniFranz, Cochabamba, Bolivia. Electronic address: arodriguezm@utp.edu.co.

 

Abstract

BACKGROUND:

Chikungunya (CHIKV) and Zika (ZIKV) significantly affected Latin America in the period 2015-2017. Most studies were reported from urban areas of Brazil and Colombia. In this paper we estimate Incidence rates for CHIKV and ZIKV in Caqueta, the Amazonian gateway area of Colombia, from 2015 to 2018.

METHODS:

Using surveillance data of CHIKV and ZIKV in Caqueta, Colombia, incidence rates were estimated (cases/100,000 population). Sixteen geographical information systems (GIS)-based municipal maps were developed. GIS software used was Kosmo 3.0®.

RESULTS:

From 1st of January 2015 to the 24th of November 2018, 825 cases of CHIK and 1079 of ZIKV were reported, yielding cumulated incidence rates of 169.42 and 221.59 cases/100,000 population respectively. In 2016, 48.7% of the CHIKV cases (402) and 96.6% of the ZIKV cases (1042) were reported. The highest number of both arboviral diseases occurred at Florencia (capital department city), 225 cases for CHIKV (127.17 cases/100,000 pop.) and 611 for ZIKV (345.34 cases/100,000 pop.).

DISCUSSION:

The temporo-spatial distribution of CHIKV and ZIKV infections in Caquetá reflected the pattern of concurrent epidemics, especially in 2016. Studies using GIS-linked maps are necessary to attain accurate epidemiological analyses for public health decisions. That is also useful for an epidemiologically based assessment of traveler risks when visiting specific areas in destination countries.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Arboviruses; Chikungunya virus (CHIKV); Geographical information systems (GIS); Infectious diseases epidemiology; Travelers; Zika virus (ZIKV)

PMID: 31521805 DOI: 10.1016/j.tmaid.2019.101481

Keywords: Zika Virus; Chikungunya fever; Colombia.

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