scholarly journals Zika Virus: Diagnostics for an Emerging Pandemic Threat

2016 ◽  
Vol 54 (4) ◽  
pp. 860-867 ◽  
Author(s):  
Jesse J. Waggoner ◽  
Benjamin A. Pinsky
Keyword(s):  
Dengue Virus ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Febrile Illness ◽  
Zikv Infection ◽  
Content Type ◽  
Clinical Criteria ◽  
Virus Diagnostics ◽  
Pandemic Threat

Zika virus (ZIKV) is anAedesmosquito-borne flavivirus that emerged in Brazil in 2015 and then rapidly spread throughout the tropical and subtropical Americas. Based on clinical criteria alone, ZIKV cannot be reliably distinguished from infections with other pathogens that cause an undifferentiated systemic febrile illness, including infections with two common arboviruses, dengue virus and chikungunya virus. This minireview details the methods that are available to diagnose ZIKV infection.

scholarly journals Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
M. J. Schultz ◽  
A. L. Tan ◽  
C. N. Gray ◽  
S. Isern ◽  
S. F. Michael ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Viral Replication ◽  
Yellow Fever ◽  
Virus Replication ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Yellow Fever Virus ◽  
Rna Viruses ◽  
Content Type ◽  
Infected Cells

ABSTRACTMosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacteriumWolbachia pipientisfrom supergroup A is a recent strategy employed to reduce the capacity for major vectors in theAedesmosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup BWolbachia wStri, isolated fromLaodelphax striatellus, was shown to inhibit multiple lineages of ZIKV inAedes albopictuscells. Here, we show thatwStri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%.wStri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited bywStri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry intowStri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate inWolbachia-infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis inwStri-infected cells. This study’s findings increase the potential for application ofwStri to block additional arboviruses and also identify specific blocks in viral infection caused byWolbachiacoinfection.IMPORTANCEDengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont,Wolbachia wStri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use ofWolbachia wStri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy.

Simultaneous detection of Dengue virus, Chikungunya virus, Zika virus, Yellow fever virus and West Nile virus

2019 ◽  
Vol 268 ◽  
pp. 53-55 ◽  
Author(s):  
José A. Boga ◽  
Marta E. Alvarez-Arguelles ◽  
Susana Rojo-Alba ◽  
Mercedes Rodríguez ◽  
María de Oña ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Yellow Fever Virus ◽  
Simultaneous Detection ◽  
Fever Virus ◽  
West Nile ◽  
Virus Zika

scholarly journals Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 72 ◽  
Author(s):  
Gustavo Cabral-Miranda ◽  
Stephanie M. Lim ◽  
Mona O. Mohsen ◽  
Ilya V. Pobelov ◽  
Elisa S. Roesti ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Clinical Manifestations ◽  
First Trimester ◽  
Neurological Complications ◽  
Zikv Infection ◽  
First Trimester Of Pregnancy ◽  
Specific Igg

Zika virus (ZIKV) is a flavivirus similar to Dengue virus (DENV) in terms of transmission and clinical manifestations, and usually both viruses are found to co-circulate. ZIKV is usually transmitted by mosquitoes bites, but may also be transmitted by blood transfusion, via the maternal–foetal route, and sexually. After 2015, when the most extensive outbreak of ZIKV had occurred in Brazil and subsequently spread throughout the rest of South America, it became evident that ZIKV infection during the first trimester of pregnancy was associated with microcephaly and other neurological complications in newborns. As a result, the development of a vaccine against ZIKV became an urgent goal. A major issue with DENV vaccines, and therefore likely also with ZIKV vaccines, is the induction of antibodies that fail to neutralize the virus properly and cause antibody-dependent enhancement (ADE) of the infection instead. It has previously been shown that antibodies against the third domain of the envelope protein (EDIII) induces optimally neutralizing antibodies with no evidence for ADE for other viral strains. Therefore, we generated a ZIKV vaccine based on the EDIII domain displayed on the immunologically optimized Cucumber mosaic virus (CuMVtt) derived virus-like particles (VLPs) formulated in dioleoyl phosphatidylserine (DOPS) as adjuvant. The vaccine induced high levels of specific IgG after a single injection. The antibodies were able to neutralise ZIKV without enhancing infection by DENV in vitro. Thus, the here described vaccine based on EDIII displayed on VLPs was able to stimulate production of antibodies specifically neutralizing ZIKV without potentially enhancing disease caused by DENV.

scholarly journals Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Charlotte A. Chang ◽  
Donald J. Hamel ◽  
Wei-Kung Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Vaccine Development ◽  
T Cell Responses ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses

ABSTRACT Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.

scholarly journals Low seroprevalence of Zika virus infection among adults in Southern Taiwan

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Wen Chien ◽  
Tzu-Chuan Ho ◽  
Pei-Wen Huang ◽  
Nai-Ying Ko ◽  
Wen-Chien Ko ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Migrant Workers ◽  
Zika Virus ◽  
Southeast Asian ◽  
Asian Countries ◽  
Zikv Infection ◽  
Serological Tests ◽  
Cross Sectional ◽  
Denv Serotypes ◽  
Southeast Asian Countries

Abstract Background We recently conducted a serosurvey of newly arrived workers in Taiwan from four Southeast Asian countries which revealed that 1% of the migrant workers had laboratory-confirmed recent Zika virus (ZIKV) infection. Taiwan, where Aedes mosquitoes are prevalent, has a close relationship with Southeast Asian countries. Up to now, 21 imported cases of ZIKV infection have been reported in Taiwan, but there has been no confirmed indigenous case. The aim of this serosurvey was to assess whether there was unrecognized ZIKV infections in Taiwan. Methods A total of 212 serum samples collected in a cross-sectional seroepidemiologic study conducted during the end of the 2015 dengue epidemic in Tainan, Taiwan, were analyzed. Anti-ZIKV IgM and IgG were tested using commercial enzyme-linked immunosorbent assays (ELISAs). Plaque reduction neutralization tests (PRNTs) for ZIKV and four dengue virus (DENV) serotypes were performed for samples with positive anti-ZIKV antibodies. A confirmed case of ZIKV infection was defined by ZIKV PRNT90 titer ratio ≥ 4 compared to four DENV serotypes. Results The mean age of the 212 participants was 54.0 years (standard deviation 13.7 years), and female was predominant (67.0%). Anti-ZIKV IgM and IgG were detected in 0 (0%) and 9 (4.2%) of the 212 participants, respectively. For the 9 samples with anti-ZIKV IgG, only 1 sample had 4 times higher ZIKV PRNT90 titers compared to PRNT90 titers against four dengue virus serotypes; this individual denied having traveled abroad. Conclusions The results suggest that undetected indigenous ZIKV transmission might have occurred in Taiwan. The findings also suggest that the threat of epidemic transmission of ZIKV in Taiwan does exist due to extremely low-level of herd immunity. Our study also indicates that serological tests for ZIKV-specific IgG remain a big challenge due to cross-reactivity, even in dengue non-endemic countries.

scholarly journals Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 307 ◽  
Author(s):  
César López-Camacho ◽  
Giuditta De Lorenzo ◽  
Jose Luis Slon-Campos ◽  
Stuart Dowall ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Protein Domain ◽  
Virus Envelope ◽  
Zikv Infection ◽  
Domain Iii ◽  
Open Question

The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.

scholarly journals A Genome-Wide CRISPR Activation Screen Identifies Genes Involved in Protection from Zika Virus Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 149
Author(s):  
Anna Dukhovny ◽  
Kevin Lamkiewicz ◽  
Qian Chen ◽  
Markus Fricke ◽  
Nabila Jabrane-Ferrat ◽  
...  
Keyword(s):  
Cell Death ◽  
Zika Virus ◽  
Early Stage ◽  
Specific Treatment ◽  
Febrile Illness ◽  
Neurological Complications ◽  
Host Factors ◽  
Zikv Infection ◽  
A Genome ◽  
Crispr Activation

Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated with the Guillain–Barré syndrome and other neurological complications. The vertical transmission of ZIKV can cause fetus demise, stillbirths or severe congenital abnormalities and neurological complications. There is still no vaccine or specific treatment for ZIKV infection. To identify the host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-lamda2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV infection. The activation of these genes had an effect at an early stage in the viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. These results highlighted a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death, thus substantiating CRISPR activation screens as a valid tool for identifying host factors impeding pathogen infection.

scholarly journals Further SAR on the (Phenylsulfonyl)piperazine Scaffold as Inhibitors of the Aedes Aegypti Kir1 (AeKir) Channel and Larvicides

2020 ◽  
Author(s):  
Christopher D. Aretz ◽  
Sujay V. Kharade ◽  
Keagan S. Chronister ◽  
Erick J. Martinez Rodriguez ◽  
Peter M. Piermarini ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Chemical Compounds ◽  
Mechanisms Of Action ◽  
Kir Channel ◽  
Primary Vector ◽  
Resistant Strains ◽  
New Compounds

We have discovered new chemical compounds that are characterized as Kir channel inhibitors of the Aedes aegypti mosquito. This is important as the Ae. aegypti mosquito is the primary vector for Zika virus (ZIKV), Dengue virus (DENV) and chikungunya virus (CHIKV). Traditional mosquitocides are plagued with significant resistance and developing new compounds with novel mechanisms of action are vitally important. Lastly, we show that our compounds are potent larvicides against pyrethroid-susceptible and pyrethroid-resistant strains.

scholarly journals Zika virus: a new pandemic threat

2016 ◽  
Vol 10 (03) ◽  
pp. 201-207 ◽  
Author(s):  
Ahmed Ali Al-Qahtani ◽  
Nyla Nazir ◽  
Mashael R. Al-Anazi ◽  
Salvatore Rubino ◽  
Mohammed N. Al-Ahdal
Keyword(s):  
Zika Virus ◽  
Blood Donation ◽  
French Polynesia ◽  
Western Hemisphere ◽  
Zikv Infection ◽  
Rapid Spread ◽  
Screening And Identification ◽  
Pandemic Threat ◽  
Contaminated Blood

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is related to dengue, Chikungunya, West Nile, yellow fever, and Japanese encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are the vectors responsible for ZIKV infection in humans. It is also reported that ZIKV is transmitted congenitally, sexually, and through blood donation. Until recently, ZIKV outbreaks were sporadic and self-limiting. The first large epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV epidemic which is rapidly spreading across the Americas. ZIKV infection remained relatively less studied in view of its low case numbers, and low clinical impact relative to other arboviruses. However, all this is set to change with its rapid spread in the Western hemisphere and suspected complications particularly microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to substantially add to both short-term and long-term economic burden of the effected countries. Due to the large number of people travelling across the borders and some reported cases of transmission of ZIKV via contaminated blood, screening and identification of asymptomatic infected individuals are important.

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