The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells

Emerging infections of mosquito-borne Zika virus (ZIKV) pose an increasing threat to human health, as documented over the recent years in South Pacific islands and the Americas in recent years. To better understand molecular mechanisms underlying the increase in human cases with severe pathologies, we recently demonstrated the functional roles of structural proteins capsid (C), pre-membrane (prM), and envelop (E) of ZIKV epidemic strains with the initiation of viral infection in human cells. Specifically, we found that the C-prM region contributes to permissiveness of human host cells to ZIKV infection and ZIKV-induced cytopathic effects, whereas the E protein is associated with viral attachment and early infection. In the present study, we further characterize ZIKV E proteins by investigating the roles of residues isoleucine 152 (Ile152), threonine 156 (Thr156), and histidine 158 (His158) (i.e., the E-152/156/158 residues), which surround a unique N-glycosylation site (E-154), in permissiveness of human host cells to epidemic ZIKV infection. For comparison purpose, we generated mutant molecular clones of epidemic BeH819015 (BR15) and historical MR766-NIID (MR766) strains that carry each other’s E-152/156/158 residues, respectively. We observed that the BR15 mutant containing the E-152/156/158 residues from MR766 was less infectious in A549-Dual™ cells than parental virus. In contrast, the MR766 mutant containing E-152/156/158 residues from BR15 displayed increased infectivity. The observed differences in infectivity were, however, not correlated with changes in viral binding onto host-cells or cellular responses to viral infection. Instead, the E-152/156/158 residues from BR15 were associated with an increased efficiency of viral membrane fusion inside infected cells due to conformational changes of E protein that enhance exposure of the fusion loop. Our data highlight an important contribution of E-152/156/158 residues to the early steps of ZIKV infection in human cells.

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Toxoplasma gondii infection induces the formation of host’s nuclear granules containing poly(A)-binding proteins

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0755 ◽

2018 ◽

Vol 64 (8) ◽

pp. 551-558 ◽

Cited By ~ 2

Author(s):

Karlee Fischer ◽

Mikayla Roberts ◽

Scott Roscoe ◽

Yasin Avci ◽

Sirinart Ananvoranich

Keyword(s):

Heat Shock ◽

Toxoplasma Gondii ◽

Viral Infection ◽

Binding Proteins ◽

Host Cells ◽

Mammalian Host ◽

Human Host ◽

Toxoplasma Gondii Infection ◽

Different Response ◽

Active Interaction

To study the mechanism by which human host cells respond to an infection of Toxoplasma gondii, we monitored the level of poly(A)-binding protein (PABP), an indicator of translation. Here, we report an observation of the relocalization of PABPs in human host cells upon T. gondii infection. Notably, the aggregates of PABPs formed upon infection are mainly found in the nucleus, which is a different response from that found after exposure to heat shock. Pyrimethamine treatment of the infected monolayers inhibits the multiplicity of the parasite and reverses the relocalization of PABP aggregates. This active interaction between the infected mammalian host cells and T. gondii appears to be different from that caused by viral infection.

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Faculty Opinions recommendation of Hitchhiking Trypanosoma cruzi minicircle DNA affects gene expression in human host cells via LINE-1 retrotransposon.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1060778.512704 ◽

2007 ◽

Author(s):

Paul J Brindley

Keyword(s):

Gene Expression ◽

Trypanosoma Cruzi ◽

Host Cells ◽

Human Host ◽

Minicircle Dna

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SARS-CoV-2 Biology Insights, Part IV.Antibody-Dependent Enhancement (ADE) and the tricky “Herd Immunity”: narrative review (Preprint)

10.2196/preprints.21599 ◽

2020 ◽

Author(s):

Laura Lafon-Hughes

Keyword(s):

Viral Infection ◽

Viral Entry ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Whooping Cough ◽

Common Knowledge ◽

Herd Immunity ◽

Life Quality ◽

Host Cells ◽

System P

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.

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Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection

Nature Communications ◽

10.1038/s41467-021-22242-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Xiaohui Wang ◽

Xiang Lin ◽

Zihan Zheng ◽

Bingtai Lu ◽

Jun Wang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Viral Infection ◽

Influenza Virus Infection ◽

Γδ T Cells ◽

T Cell Response ◽

Host Cells ◽

Interleukin 17 ◽

Γδ T Cell ◽

Innate Defense

AbstractInnate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing γδ T (Tγδ17) cells with a phenotype of TCRγδhiCD3hiAQP3hiCXCR6hi in both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d+ B-1a cells to activate IL-17A production in γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection.

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Modelling Degradation and Replication Kinetics of the Zika Virus In Vitro Infection

Viruses ◽

10.3390/v12050547 ◽

2020 ◽

Vol 12 (5) ◽

pp. 547

Author(s):

Veronika Bernhauerová ◽

Veronica V. Rezelj ◽

Marco Vignuzzi

Keyword(s):

Mathematical Model ◽

Viral Infection ◽

Host Cell ◽

Decay Time ◽

Zika Virus ◽

Infectious Virus ◽

Numerical Characterization ◽

The Mathematical Model

Mathematical models of in vitro viral kinetics help us understand and quantify the main determinants underlying the virus–host cell interactions. We aimed to provide a numerical characterization of the Zika virus (ZIKV) in vitro infection kinetics, an arthropod-borne emerging virus that has gained public recognition due to its association with microcephaly in newborns. The mathematical model of in vitro viral infection typically assumes that degradation of extracellular infectious virus proceeds in an exponential manner, that is, each viral particle has the same probability of losing infectivity at any given time. We incubated ZIKV stock in the cell culture media and sampled with high frequency for quantification over the course of 96 h. The data showed a delay in the virus degradation in the first 24 h followed by a decline, which could not be captured by the model with exponentially distributed decay time of infectious virus. Thus, we proposed a model, in which inactivation of infectious ZIKV is gamma distributed and fit the model to the temporal measurements of infectious virus remaining in the media. The model was able to reproduce the data well and yielded the decay time of infectious ZIKV to be 40 h. We studied the in vitro ZIKV infection kinetics by conducting cell infection at two distinct multiplicity of infection and measuring viral loads over time. We fit the mathematical model of in vitro viral infection with gamma distributed degradation time of infectious virus to the viral growth data and identified the timespans and rates involved within the ZIKV-host cell interplay. Our mathematical analysis combined with the data provides a well-described example of non-exponential viral decay dynamics and presents numerical characterization of in vitro infection with ZIKV.

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The Use of Lectins as Tools to Combat SARS-CoV-2

Current Pharmaceutical Design ◽

10.2174/1381612827666210830094743 ◽

2021 ◽

Vol 27 ◽

Author(s):

Daniela Martinez ◽

Diego Amaral ◽

David Markovitz ◽

Luciano Pinto

Keyword(s):

Viral Infection ◽

Host Cells ◽

Viral Fusion ◽

Cell Receptors ◽

First Case ◽

Mannose Binding ◽

New Treatments ◽

Viral Surface

Background: in december 2019, china announced the first case of an infection caused by an, until then, unknown virus: sars-cov-2. since then, researchers have been looking for viable alternatives for the treatment and/or cure of viral infection. among the possible complementary solutions are lectins, and proteins that are reversibly bound to different carbohydrates. the spike protein, present on the viral surface, can interact with different cell receptors: ace2, cd147, and dc-signr. since lectins have an affinity for different carbohydrates, the binding with the glycosylated cell receptors represents a possibility of preventing the virus from binding to the receptors of host cells. Objective: in this review we discuss the main lectins that are possible candidates for use in the treatment of covid-19, highlighting those that have already demonstrated antiviral activity in vivo and in vitro, including mannose-binding lectin, griffithsin, banlec, and others. we also aim to discuss the possible mechanism of action of lectins, which appears to occur through the mediation of viral fusion in host cells, by binding of lectins to glycosylated receptors found in human cells and/or binding of these proteins with the spike glycoprotein, present in virus surface.moreover, we also discuss the use of lectins in clinical practice. Conclusion: Even with the development of effective vaccines, new cases of viral infection with the same virus, or new outbreaks with different viruses can occur; so, the development of new treatments should not be discarded. moreover, the discussions made in this work are relevant regarding the anti-viral properties of lectins.

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A Biomimetic Nanodecoy Traps Zika Virus To Prevent Viral Infection and Fetal Microcephaly Development

Nano Letters ◽

10.1021/acs.nanolett.8b03913 ◽

2018 ◽

Vol 19 (4) ◽

pp. 2215-2222 ◽

Cited By ~ 18

Author(s):

Lang Rao ◽

Wenbiao Wang ◽

Qian-Fang Meng ◽

Mingfu Tian ◽

Bo Cai ◽

...

Keyword(s):

Viral Infection ◽

Zika Virus

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Tumour viruses and innate immunity

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0267 ◽

2017 ◽

Vol 372 (1732) ◽

pp. 20160267 ◽

Cited By ~ 13

Author(s):

Sharon E. Hopcraft ◽

Blossom Damania

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Viral Infection ◽

Innate Immune Response ◽

Innate Immune ◽

Host Cells ◽

Oncogenic Viruses ◽

Barr Virus ◽

Human T Cell ◽

Epstein Barr

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system. This article is part of the themed issue ‘Human oncogenic viruses’.

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