scholarly journals Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for Vaccine Design

2017 ◽  
Vol 91 (20) ◽  
Author(s):  
Qihui Wang ◽  
Jinghua Yan ◽  
George Fu Gao
Keyword(s):  
Monoclonal Antibodies ◽  
Zika Virus ◽  
Hot Spots ◽  
Vaccine Design ◽  
Neurological Complications ◽  
Complete Picture ◽  
Structural Studies ◽  
Zikv Infection ◽  
Short Period ◽  
Global Concern

ABSTRACT Zika virus (ZIKV) has caused global concern due to its association with neurological complications in newborns and adults. Although no vaccines or antivirals against ZIKV infection have been approved to date, hundreds of monoclonal antibodies (MAbs) have been developed in a short period. Here, we first present a complete picture of the ZIKV MAbs and then focus on the neutralizing mechanisms and immune hot spots uncovered through structural studies, which provide insight for therapeutics and vaccine design.

scholarly journals Pregnancy and Zika virus

2020 ◽  
Vol 14 (2) ◽  
pp. 229-238
Author(s):  
T. V. Startseva ◽  
N. N. Kanshina ◽  
M. V. Tretyakova ◽  
V. O. Bitsadze ◽  
J. Kh. Khizroeva ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Asymptomatic Carrier ◽  
Clinical Signs ◽  
Neurological Complications ◽  
Zikv Infection ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Urban Cycle

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the Flaviviridae family. In 1947 and 1948 ZIKV was first isolated from a nonhuman primate as well as from mosquitoes in Africa, respectively. For half a century, ZIKV infections in human were sporadic prior to 2015–2016 pandemic spreading. Transmission of ZIKV from mother to fetus can occur in any trimester of pregnancy, even if mother was an asymptomatic carrier. The clinical signs of ZIKV infection are nonspecific and can be misdiagnosed as some other infectious diseases, especially those caused by arboviruses such as Dengue and Chikungunya. ZIKV infection was solely associated with mild illness prior to the large French Polynesian and Brazil outbreaks, when severe neurological complications, Guillain–Barre syndrome and dramatically increased rate of severe congenital malformations (including microcephaly) were reported. The adaptation of ZIKV to an urban cycle in endemic areas suggests that the incidence of ZIKV infections may be underestimated. The pandemic of novel coronavirus infection (COVID-19) demonstrates that lessons from ZIKV pandemic propagation has not been learned properly.

scholarly journals Vector Competence: What Has Zika Virus Taught Us?

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 867 ◽  
Author(s):  
Sasha R. Azar ◽  
Scott C. Weaver
Keyword(s):  
Experimental Design ◽  
Zika Virus ◽  
Vector Competence ◽  
Large Body ◽  
Large Data ◽  
Mosquito Vector ◽  
Zikv Infection ◽  
Data Set ◽  
Short Period ◽  
Meta Analyses

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.

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 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 N-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Vivian V. Costa ◽  
Juliana L. Del Sarto ◽  
Rebeca F. Rocha ◽  
Flavia R. Silva ◽  
Juliana G. Doria ◽  
...  
Keyword(s):  
Global Health ◽  
Drug Treatment ◽  
Zika Virus ◽  
Neuronal Death ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Zikv Infection ◽  
Experimental Animals

ABSTRACT Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo. These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo. These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment.

scholarly journals ADP-Ribosyltransferase PARP11 Suppresses Zika Virus in Synergy with PARP12

2021 ◽  
Author(s):  
Lili Li ◽  
Yueyue Shi ◽  
Sirui Li ◽  
Junxiao Liu ◽  
Shulong Zu ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neurological Complications ◽  
Host Cells ◽  
Interferon Response ◽  
Type I ◽  
Zikv Infection ◽  
Interferon Stimulated Genes ◽  
Ns3 Protein ◽  
Global Threat ◽  
Adp Ribosyltransferase

Abstract Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. ZIKV infection stimulates type I interferon response in host cells which suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs). Here, we identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that PARP11 suppressed ZIKV independently on itself PARP enzyme activity. Furthermore, PARP11 interacted with PARP12 and promoted PARP12-mediating ZIKV NS1 and NS3 protein degradation. Homo family PARP11 and PARP12 cooperated with each other on ZIKV suppression and the anti-ZIKV function of PARP11 mostly dependent on the existence of PARP12. Our findings have broadened the understanding of the anti-viral function of PARP11, and more importantly suggest a potential therapeutics target against ZIKV infection.

scholarly journals Guillain-Barré syndrome associated with the Zika virus outbreak in Brazil

2016 ◽  
Vol 74 (3) ◽  
pp. 253-255 ◽  
Author(s):  
Lucas Masiêro Araujo ◽  
Maria Lucia Brito Ferreira ◽  
Osvaldo JM Nascimento
Keyword(s):  
Zika Virus ◽  
French Polynesia ◽  
Neurological Complications ◽  
Standard Test ◽  
Guillain Barre Syndrome ◽  
Zikv Infection ◽  
Resource Limited ◽  
Guillain Barré Syndrome ◽  
Large Outbreak ◽  
Guillain Barré

ABSTRACT Zika virus (ZIKV) is now considered an emerging flavivirosis, with a first large outbreak registered in the Yap Islands in 2007. In 2013, a new outbreak was reported in the French Polynesia, with associated cases of neurological complications including Guillain-Barré syndrome (GBS). The incidence of GBS has increased in Brazil since 2015, what is speculated to be secondary to the ZIKV infection outbreak. The gold-standard test for detection of acute ZIKV infection is the polymerase-chain reaction technique, an essay largely unavailable in Brazil. The diagnosis of GBS is feasible even in resource-limited areas using the criteria proposed by the GBS Classification Group, which is based solely on clinical grounds. Further understanding on the relationship of ZIKV with neurological complications is a research urgency.

scholarly journals Characterization of cis-Acting RNA Elements of Zika Virus by Using a Self-Splicing Ribozyme-Dependent Infectious Clone

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Zhong-Yu Liu ◽  
Jiu-Yang Yu ◽  
Xing-Yao Huang ◽  
Hang Fan ◽  
Xiao-Feng Li ◽  
...  
Keyword(s):  
Zika Virus ◽  
Reverse Genetics ◽  
Infectious Clone ◽  
Neurological Complications ◽  
Cdna Clones ◽  
Content Type ◽  
Infectious Clones ◽  
Global Concern ◽  
Rna Elements ◽  
Self Splicing

ABSTRACT Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in Escherichia coli hosts has hindered the development of ZIKV infectious clones. Here, using a novel self-splicing ribozyme-based strategy, we generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016. The constructed clone contained a modified version of the group II self-splicing intron P.li.LSUI2 near the junction between the E and NS1 genes, which were removed from the RNA transcripts by an easy-to-establish in vitro splicing reaction. Transfection of the spliced RNAs into BHK-21 cells led to the production of infectious progeny virus that resembled the parental virus. Finally, potential cis-acting RNA elements in ZIKV genomic RNA were identified based on this novel reverse genetics system, and the critical role of 5′-SLA promoter and 5′-3′ cyclization sequences were characterized by a combination of different assays. Our results provide another stable and reliable reverse genetics system for ZIKV that will help study ZIKV infection and pathogenesis, and the novel self-splicing intron-based strategy could be further expanded for the construction of infectious clones from other emerging and reemerging flaviviruses. IMPORTANCE The ongoing Zika virus (ZIKV) outbreaks have drawn global concern due to the unexpected causal link to fetus microcephaly and other severe neurological complications. The infectious cDNA clones of ZIKV are critical for the research community to study the virus, understand the disease, and inform vaccine design and antiviral screening. A panel of existing technologies have been utilized to develop ZIKV infectious clones. Here, we successfully generated a stable infectious clone of a 2016 ZIKV strain using a novel self-splicing ribozyme-based technology that abolished the potential toxicity of ZIKV cDNA clones to the E. coli host. Moreover, two crucial cis-acting replication elements (5′-SLA and 5′-CS) of ZIKV were first identified using this novel reverse genetics system. This novel self-splicing ribozyme-based reverse genetics platform will be widely utilized in future ZIKV studies and provide insight for the development of infectious clones of other emerging viruses.

scholarly journals Late Neurological Consequences of Zika Virus Infection: Risk Factors and Pharmaceutical Approaches

2019 ◽  
Vol 12 (2) ◽  
pp. 60 ◽  
Author(s):  
Isis N. O. Souza ◽  
Fernanda G. Q. Barros-Aragão ◽  
Paula S. Frost ◽  
Claudia P. Figueiredo ◽  
Julia R. Clarke
Keyword(s):  
Zika Virus ◽  
Late Onset ◽  
Neurological Complications ◽  
Therapeutic Approaches ◽  
Zikv Infection ◽  
Clinical Surveillance ◽  
Infection Risk Factors

Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in adult patients, have been reported after ZIKV infection, especially after the 2015 epidemics in the American continent. The development or severity of these conditions cannot be fully predicted, but it is possible that genetic, epigenetic, and environmental factors may contribute to determine ZIKV infection outcomes. This reinforces the importance that individuals exposed to ZIKV are submitted to long-term clinical surveillance and highlights the urgent need for the development of therapeutic approaches to reduce or eliminate the neurological burden of infection. Here, we review the epidemiology of ZIKV-associated neurological complications and the role of factors that may influence disease outcome. Moreover, we discuss experimental and clinical evidence of drugs that have shown promising results in vitro or in vitro against viral replication and and/or ZIKV-induced neurotoxicity.

scholarly journals Resveratrol affects Zika virus replication in vitro

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Azirah Mohd ◽  
Nurhafiza Zainal ◽  
Kim-Kee Tan ◽  
Sazaly AbuBakar
Keyword(s):  
Cell Cultures ◽  
Zika Virus ◽  
Copy Number ◽  
Virus Titer ◽  
Health Concern ◽  
Dependent Manner ◽  
Zikv Infection ◽  
Mrna Copy Number ◽  
Short Period

Abstract Zika virus (ZIKV) infection is a serious public health concern. ZIKV infection has been associated with increased occurrences of microcephaly among newborns and incidences of Guillain-Barré syndrome among adults. No specific therapeutics or vaccines are currently available to treat and protect against ZIKV infection. Here, a plant-secreted phytoalexin, resveratrol (RES), was investigated for its ability to inhibit ZIKV replication in vitro. Several RES treatment regimens were used. The ZIKV titers of mock- and RES-treated infected cell cultures were determined using the focus-forming assay and the Zika mRNA copy number as determined using qRT-PCR. Our results suggested that RES treatment reduced ZIKV titers in a dose-dependent manner. A reduction of >90% of virus titer and ZIKV mRNA copy number was achieved when infected cells were treated with 80 µM of RES post-infection. Pre-incubation of the virus with 80 µM RES showed >30% reduction in ZIKV titers and ZIKV mRNA copy number, implying potential direct virucidal effects of RES against the virus. The RES treatment reduced >70% virus titer in the anti-adsorption assay, suggesting the possibility that RES also interferes with ZIKV binding. However, there was no significant decrease in ZIKV titer when a short-period of RES treatment was applied to cells before ZIKV infection (pre-infection) and after the virus bound to the cells (virus internalization inhibition), implying that RES acts through its continuous presence in the cell cultures after virus infection. Overall, our results suggested that RES exhibited direct virucidal activity against ZIKV and possessed anti-ZIKV replication properties, highlighting the need for further exploration of RES as a potential antiviral molecule against ZIKV infection.

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