scholarly journals Viperin Restricts Zika Virus and Tick-Borne Encephalitis Virus Replication by Targeting NS3 for Proteasomal Degradation

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Christakis Panayiotou ◽  
Richard Lindqvist ◽  
Chaitanya Kurhade ◽  
Kirstin Vonderstein ◽  
Jenny Pasto ◽  
...  
Keyword(s):  
Therapeutic Intervention ◽  
Zika Virus ◽  
Viral Proteins ◽  
Encephalitis Virus ◽  
Content Type ◽  
Tick Borne Encephalitis ◽  
Ns3 Protein ◽  
Tick Borne Encephalitis Virus ◽  
The Stability ◽  
Antiviral Mechanism

ABSTRACTFlaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum associated, IFN inducible), which shows antiviral activity against a broad spectrum of viruses, including several flaviviruses. Here we describe a novel antiviral mechanism employed by viperin against two prominent flaviviruses, tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin was found to interact and colocalize with the structural proteins premembrane (prM) and envelope (E) of TBEV, as well as with nonstructural (NS) proteins NS2A, NS2B, and NS3. Interestingly, viperin expression reduced the NS3 protein level, and the stability of the other interacting viral proteins, but only in the presence of NS3. We also found that although viperin interacted with NS3 of mosquito-borne flaviviruses (ZIKV, Japanese encephalitis virus, and yellow fever virus), only ZIKV was sensitive to the antiviral effect of viperin. This sensitivity correlated with viperin's ability to induce proteasome-dependent degradation of NS3. ZIKV and TBEV replication was rescued completely when NS3 was overexpressed, suggesting that the viral NS3 is the specific target of viperin. In summary, we present here a novel antiviral mechanism of viperin that is selective for specific viruses in the genusFlavivirus, affording the possible availability of new drug targets that can be used for therapeutic intervention.IMPORTANCEFlaviviruses are a group of enveloped RNA viruses that cause severe diseases in humans and animals worldwide, but no antiviral treatment is yet available. Viperin, a host protein produced in response to infection, effectively restricts the replication of several flaviviruses, but the exact molecular mechanisms have not been elucidated. Here we have identified a novel mechanism employed by viperin to inhibit the replication of two flaviviruses: tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin induced selective degradation via the proteasome of TBEV and ZIKV nonstructural 3 (NS3) protein, which is involved in several steps of the viral life cycle. Furthermore, viperin also reduced the stability of several other viral proteins in a NS3-dependent manner, suggesting a central role of NS3 in viperin's antiflavivirus activity. Taking the results together, our work shows important similarities and differences among the members of the genusFlavivirusand could lead to the possibility of therapeutic intervention.

scholarly journals A short form of the tick-borne encephalitis virus NS3 protein

FEBS Letters ◽  
1992 ◽  
Vol 297 (1-2) ◽  
pp. 67-69 ◽  
Author(s):  
K.V. Pugachev ◽  
N.Yu. Nomokonova ◽  
O.V. Morozova ◽  
A.G. Pletnev
Keyword(s):  
Short Form ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Ns3 Protein ◽  
Tick Borne Encephalitis Virus

scholarly journals Tick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection In Vitro and in a Mouse Model

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
James Duehr ◽  
Silviana Lee ◽  
Gursewak Singh ◽  
Gregory A. Foster ◽  
David Krysztof ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dengue Virus ◽  
Human Plasma ◽  
Mouse Models ◽  
Zika Virus ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

ABSTRACT Recent reports in the scientific literature have suggested that anti-dengue virus (DENV) and anti-West Nile virus (WNV) immunity exacerbates Zika virus (ZIKV) pathogenesis in vitro and in vivo in mouse models. Large populations of immune individuals exist for a related flavivirus (tick-borne encephalitis virus [TBEV]), due to large-scale vaccination campaigns and endemic circulation throughout most of northern Europe and the southern Russian Federation. As a result, the question of whether anti-TBEV immunity can affect Zika virus pathogenesis is a pertinent one. For this study, we obtained 50 serum samples from individuals vaccinated with the TBEV vaccine FSME-IMMUN (Central European/Neudörfl strain) and evaluated their enhancement capacity in vitro using K562 human myeloid cells expressing CD32 and in vivo using a mouse model of ZIKV pathogenesis. Among the 50 TBEV vaccinee samples evaluated, 29 had detectable reactivity against ZIKV envelope (E) protein by enzyme-linked immunosorbent assay (ELISA), and 36 showed enhancement of ZIKV infection in vitro. A pool of the most highly reacting and enhanced samples resulted in no significant change in the morbidity/mortality of ZIKV disease in immunocompromised Stat2−/− mice. Our results suggest that humoral immunity against TBEV is unlikely to enhance Zika virus pathogenesis in humans. No clinical reports indicating that TBEV vaccinees experiencing enhanced ZIKV disease have been published so far, and though the epidemiological data are sparse, our findings suggest that there is little reason for concern. This study also displays a clear relationship between the phylogenetic distance between two flaviviruses and their capacity for pathogenic enhancement. IMPORTANCE The relationship between serial infections of two different serotypes of dengue virus and more severe disease courses is well-documented in the literature, driven by so-called antibody-dependent enhancement (ADE). Recently, studies have shown the possibility of ADE in cells exposed to anti-DENV human plasma and then infected with ZIKV and also in mouse models of ZIKV pathogenesis after passive transfer of anti-DENV human plasma. In this study, we evaluated the extent to which this phenomenon occurs using sera from individuals immunized against tick-borne encephalitis virus (TBEV). This is highly relevant, since large proportions of the European population are vaccinated against TBEV or otherwise seropositive.

scholarly journals Flaviviridae Viruses and Oxidative Stress: Implications for Viral Pathogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Liang Rong ◽  
Yi-Ping Li
Keyword(s):  
Oxidative Stress ◽  
Life Cycle ◽  
Viral Proteins ◽  
Viral Pathogenesis ◽  
Encephalitis Virus ◽  
Research Attention ◽  
Molecular Events ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
And Oxidative Stress

Oxidative stress is induced once the balance of generation and neutralization of reactive oxygen species (ROS) is broken in the cell, and it plays crucial roles in a variety of natural and diseased processes. Infections of Flaviviridae viruses trigger oxidative stress, which affects both the cellular metabolism and the life cycle of the viruses. Oxidative stress associated with specific viral proteins, experimental culture systems, and patient infections, as well as its correlations with the viral pathogenesis attracts much research attention. In this review, we primarily focus on hepatitis C virus (HCV), dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) as representatives of Flaviviridae viruses and we summarize the mechanisms involved in the relevance of oxidative stress for virus-associated pathogenesis. We discuss the current understanding of the pathogenic mechanisms of oxidative stress induced by Flaviviridae viruses and highlight the relevance of autophagy and DNA damage in the life cycle of viruses. Understanding the crosstalk between viral infection and oxidative stress-induced molecular events may offer new avenues for antiviral therapeutics.

scholarly journals Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans

2021 ◽  
Vol 11 ◽  
Author(s):  
Marcilio Jorge Fumagalli ◽  
Luiz Tadeu Moraes Figueiredo ◽  
Victor Hugo Aquino
Keyword(s):  
West Nile Virus ◽  
Viral Proteins ◽  
Encephalitis Virus ◽  
Vaccine Formulation ◽  
Valuable Data ◽  
Tick Borne Encephalitis ◽  
Virus West Nile ◽  
Tick Borne Encephalitis Virus ◽  
Virus Zika ◽  
Flavivirus Infection

This manuscript is an up-to-date review of experimentally validated linear and continuous epitopes identified from arbovirus members of the Flavivirus genus. We summarized 153 immunoreactive peptides from the Dengue virus, Zika virus, Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus described in studies published from 1989 to 2020. We included peptides from structural (envelope, capsid, and pre-membrane) and nonstructural (Ns1–5) viral proteins that demonstrated relevant immunoreactivity with antibodies from naturally infected or vaccinated humans. We included peptides that demonstrated relevant reactivity features, such as indicators of disease severity related to immunological or immunopathological outcomes, differential or group diagnostic markers, immunotherapy candidates, and potential for vaccine formulation. The majority of immunoreactive peptides were described for DENV probably due to its long-lasting impact on human health and the lack of efficient vaccines and therapeutic methods. Immune landscape data regarding linear immunoreactive and continuous flavivirus peptides are still scarce, and a complete and more detailed map remains to be elucidated. Therefore, this review provides valuable data for those investigating the antibody response against flavivirus infection.

scholarly journals Virtual screening of inhibitors for the Zika virus proteins

2016 ◽  
Author(s):  
S. Feranchuk ◽  
U. Potapova ◽  
S. Belikov
Keyword(s):  
Virtual Screening ◽  
Antiviral Therapy ◽  
Zika Virus ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Ns3 Protease ◽  
Virus Proteins

AbstractThe NS3 protease and NS5 polymerase structures of the Zika virus were constructed and processed using a virtual screening pipeline. MM-PBSA calculations show that some of the ligands found by the pipeline demonstrate a good affinity to vulnerable sites in both proteins. The anti-hypertension drug eprosartan is among the selected ligands; and inhibition of the tick-borne encephalitis virus has already been confirmed in vivo by a previous study. In the present study phytochemicals bisabolol and andrographolide are suggested as the candidates for antiviral therapy.

TBE in South Korea

2019 ◽  
Author(s):  
Joon Young Song
Keyword(s):  
South Korea ◽  
Human Case ◽  
Encephalitis Virus ◽  
Surveillance Studies ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Although no human case of tick-borne encephalitis (TBE) has been documented in South Korea to date, surveillance studies have been conducted to evaluate the prevalence of tick-borne encephalitis virus (TBEV) in wild ticks.

TBE in Slovakia

2019 ◽  
Author(s):  
Jana Kerlik
Keyword(s):  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

The former Czechoslovak Republic was one of the first countries in Europe where the tick-borne encephalitis virus (TBEV) was identified.

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