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1.
Front Immunol ; 13: 826091, 2022.
Article in English | MEDLINE | ID: covidwho-1731778

ABSTRACT

Neural stem cells (NSCs) are multipotent stem cells that reside in the fetal and adult mammalian brain, which can self-renew and differentiate into neurons and supporting cells. Intrinsic and extrinsic cues, from cells in the local niche and from distant sites, stringently orchestrates the self-renewal and differentiation competence of NSCs. Ample evidence supports the important role of NSCs in neuroplasticity, aging, disease, and repair of the nervous system. Indeed, activation of NSCs or their transplantation into injured areas of the central nervous system can lead to regeneration in animal models. Viral invasion of NSCs can negatively affect neurogenesis and synaptogenesis, with consequent cell death, impairment of cell cycle progression, early differentiation, which cause neural progenitors depletion in the cortical layer of the brain. Herein, we will review the current understanding of Zika virus (ZIKV) infection of the fetal brain and the NSCs, which are the preferential population targeted by ZIKV. Furthermore, the potential neurotropic properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may cause direct neurological damage, will be discussed.


Subject(s)
Brain/virology , COVID-19/pathology , COVID-19/virology , Neurogenesis/physiology , Neurons/virology , Zika Virus Infection/pathology , Zika Virus Infection/virology , Animals , Humans , Neural Stem Cells/virology
2.
Biochemistry ; 60(46): 3449-3451, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1590174

ABSTRACT

Single-particle cryogenic electron microscopy (cryo-EM), whose full power was not realized until the advent of powerful detectors in 2012, has a unique position as a method of structure determination as it is capable of providing information about not only the structure but also the dynamical features of biomolecules. This information is of special importance in understanding virus-host interaction and explains the crucial role of cryo-EM in the efforts to find vaccinations and cures for pandemics the world has experienced in the past decade.


Subject(s)
Cryoelectron Microscopy , Host Microbial Interactions , Single Molecule Imaging , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Dengue/epidemiology , Dengue/prevention & control , Dengue/virology , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/virology , Humans , Pandemics/prevention & control , Viral Vaccines/administration & dosage , Zika Virus Infection/epidemiology , Zika Virus Infection/prevention & control , Zika Virus Infection/virology
3.
Viruses ; 13(11)2021 10 26.
Article in English | MEDLINE | ID: covidwho-1488755

ABSTRACT

Understanding the dynamic relationship between viral pathogens and cellular host factors is critical to furthering our knowledge of viral replication, disease mechanisms and development of anti-viral therapeutics. CRISPR genome editing technology has enhanced this understanding, by allowing identification of pro-viral and anti-viral cellular host factors for a wide range of viruses, most recently the cause of the COVID-19 pandemic, SARS-CoV-2. This review will discuss how CRISPR knockout and CRISPR activation genome-wide screening methods are a robust tool to investigate the viral life cycle and how other class 2 CRISPR systems are being repurposed for diagnostics.


Subject(s)
CRISPR-Cas Systems , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/genetics , Gene Editing , Zika Virus Infection/virology , Zika Virus/genetics , COVID-19/diagnosis , COVID-19/virology , Clustered Regularly Interspaced Short Palindromic Repeats , Communicable Diseases, Emerging/diagnosis , Coronavirus/physiology , Coronavirus Infections/diagnosis , Host-Pathogen Interactions , Humans , SARS-CoV-2/genetics , Zika Virus/physiology , Zika Virus Infection/diagnosis
4.
J Virol ; 95(24): e0059621, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1443352

ABSTRACT

Cellular factors have important roles in all facets of the flavivirus replication cycle. Deciphering viral-host protein interactions is essential for understanding the flavivirus life cycle as well as development of effective antiviral strategies. To uncover novel host factors that are co-opted by multiple flaviviruses, a CRISPR/Cas9 genome wide knockout (KO) screen was employed to identify genes required for replication of Zika virus (ZIKV). Receptor for Activated Protein C Kinase 1 (RACK1) was identified as a novel host factor required for ZIKV replication, which was confirmed via complementary experiments. Depletion of RACK1 via siRNA demonstrated that RACK1 is important for replication of a wide range of mosquito- and tick-borne flaviviruses, including West Nile Virus (WNV), Dengue Virus (DENV), Powassan Virus (POWV) and Langat Virus (LGTV) as well as the coronavirus SARS-CoV-2, but not for YFV, EBOV, VSV or HSV. Notably, flavivirus replication was only abrogated when RACK1 expression was dampened prior to infection. Utilising a non-replicative flavivirus model, we show altered morphology of viral replication factories and reduced formation of vesicle packets (VPs) in cells lacking RACK1 expression. In addition, RACK1 interacted with NS1 protein from multiple flaviviruses; a key protein for replication complex formation. Overall, these findings reveal RACK1's crucial role to the biogenesis of pan-flavivirus replication organelles. IMPORTANCE Cellular factors are critical in all facets of viral lifecycles, where overlapping interactions between the virus and host can be exploited as possible avenues for the development of antiviral therapeutics. Using a genome-wide CRISPR knockout screening approach to identify novel cellular factors important for flavivirus replication we identified RACK1 as a pro-viral host factor for both mosquito- and tick-borne flaviviruses in addition to SARS-CoV-2. Using an innovative flavivirus protein expression system, we demonstrate for the first time the impact of the loss of RACK1 on the formation of viral replication factories known as 'vesicle packets' (VPs). In addition, we show that RACK1 can interact with numerous flavivirus NS1 proteins as a potential mechanism by which VP formation can be induced by the former.


Subject(s)
CRISPR-Cas Systems , Flavivirus/genetics , Neoplasm Proteins/genetics , Receptors for Activated C Kinase/genetics , Virus Replication , A549 Cells , Aedes , Animals , COVID-19 , Chlorocebus aethiops , Culicidae , Dengue Virus/genetics , Genome-Wide Association Study , HEK293 Cells , Host-Pathogen Interactions/genetics , Humans , RNA, Small Interfering/metabolism , RNA, Viral/metabolism , SARS-CoV-2 , Vero Cells , West Nile virus/genetics , Zika Virus/genetics , Zika Virus Infection/virology
5.
Viruses ; 13(8)2021 08 18.
Article in English | MEDLINE | ID: covidwho-1376994

ABSTRACT

Viral infection is a global public health threat causing millions of deaths. A suitable small animal model is essential for viral pathogenesis and host response studies that could be used in antiviral and vaccine development. The tree shrew (Tupaia belangeri or Tupaia belangeri chinenesis), a squirrel-like non-primate small mammal in the Tupaiidae family, has been reported to be susceptible to important human viral pathogens, including hepatitis viruses (e.g., HBV, HCV), respiratory viruses (influenza viruses, SARS-CoV-2, human adenovirus B), arboviruses (Zika virus and dengue virus), and other viruses (e.g., herpes simplex virus, etc.). The pathogenesis of these viruses is not fully understood due to the lack of an economically feasible suitable small animal model mimicking natural infection of human diseases. The tree shrew model significantly contributes towards a better understanding of the infection and pathogenesis of these important human pathogens, highlighting its potential to be used as a viable viral infection model of human viruses. Therefore, in this review, we summarize updates regarding human viral infection in the tree shrew model, which highlights the potential of the tree shrew to be utilized for human viral infection and pathogenesis studies.


Subject(s)
Disease Models, Animal , Tupaia , Virus Diseases , Adenoviridae Infections/immunology , Adenoviridae Infections/virology , Animals , COVID-19/virology , Dengue/immunology , Dengue/pathology , Dengue/virology , HIV Infections/virology , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis C/immunology , Hepatitis C/pathology , Hepatitis C/virology , Herpes Simplex/pathology , Herpes Simplex/virology , Humans , Influenza, Human/immunology , Influenza, Human/virology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Zika Virus Infection/immunology , Zika Virus Infection/pathology , Zika Virus Infection/virology
6.
Science ; 373(6551): 231-236, 2021 07 09.
Article in English | MEDLINE | ID: covidwho-1304152

ABSTRACT

In mammals, early resistance to viruses relies on interferons, which protect differentiated cells but not stem cells from viral replication. Many other organisms rely instead on RNA interference (RNAi) mediated by a specialized Dicer protein that cleaves viral double-stranded RNA. Whether RNAi also contributes to mammalian antiviral immunity remains controversial. We identified an isoform of Dicer, named antiviral Dicer (aviD), that protects tissue stem cells from RNA viruses-including Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-by dicing viral double-stranded RNA to orchestrate antiviral RNAi. Our work sheds light on the molecular regulation of antiviral RNAi in mammalian innate immunity, in which different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.


Subject(s)
DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , RNA Interference , RNA Viruses/physiology , RNA, Viral/metabolism , Ribonuclease III/genetics , Ribonuclease III/metabolism , Stem Cells/enzymology , Stem Cells/virology , Alternative Splicing , Animals , Brain/enzymology , Brain/virology , Cell Line , DEAD-box RNA Helicases/chemistry , Humans , Immunity, Innate , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Mice , Organoids/enzymology , Organoids/virology , RNA Virus Infections/enzymology , RNA Virus Infections/immunology , RNA Virus Infections/virology , RNA Viruses/genetics , RNA Viruses/immunology , RNA, Double-Stranded/metabolism , RNA, Small Interfering/metabolism , Ribonuclease III/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Virus Replication , Zika Virus/genetics , Zika Virus/immunology , Zika Virus/physiology , Zika Virus Infection/enzymology , Zika Virus Infection/immunology , Zika Virus Infection/virology
7.
BMC Med Res Methodol ; 21(1): 50, 2021 03 11.
Article in English | MEDLINE | ID: covidwho-1133581

ABSTRACT

BACKGROUND: Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, and in 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 2019 (COVID-19). We compared patterns of scientific publications for the two infections to analyse the evolution of the evidence. METHODS: We annotated publications on Zika virus and SARS-CoV-2 that we collected using living evidence databases according to study design. We used descriptive statistics to categorise and compare study designs over time. RESULTS: We found 2286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 24 May 2020, of which we analysed a random sample of 5294 (24%). For both infections, there were more epidemiological than laboratory science studies. Amongst epidemiological studies for both infections, case reports, case series and cross-sectional studies emerged first, cohort and case-control studies were published later. Trials were the last to emerge. The number of preprints was much higher for SARS-CoV-2 than for Zika virus. CONCLUSIONS: Similarities in the overall pattern of publications might be generalizable, whereas differences are compatible with differences in the characteristics of a disease. Understanding how evidence accumulates during disease outbreaks helps us understand which types of public health questions we can answer and when.


Subject(s)
COVID-19/prevention & control , Publications/statistics & numerical data , Publications/trends , SARS-CoV-2/isolation & purification , Zika Virus Infection/prevention & control , Zika Virus/isolation & purification , COVID-19/epidemiology , COVID-19/virology , Case-Control Studies , Cross-Sectional Studies , Disease Outbreaks , Humans , Pandemics , Periodicals as Topic/statistics & numerical data , Periodicals as Topic/trends , SARS-CoV-2/physiology , Zika Virus/physiology , Zika Virus Infection/epidemiology , Zika Virus Infection/virology
8.
PLoS Negl Trop Dis ; 15(3): e0009259, 2021 03.
Article in English | MEDLINE | ID: covidwho-1127761

ABSTRACT

Dengue, Zika and chikungunya are diseases of global health significance caused by arboviruses and transmitted by the mosquito Aedes aegypti, which is of worldwide circulation. The arrival of the Zika and chikungunya viruses to South America increased the complexity of transmission and morbidity caused by these viruses co-circulating in the same vector mosquito species. Here we present an integrated analysis of the reported arbovirus cases between 2007 and 2017 and local climate and socio-economic profiles of three distinct Colombian municipalities (Bello, Cúcuta and Moniquirá). These locations were confirmed as three different ecosystems given their contrasted geographic, climatic and socio-economic profiles. Correlational analyses were conducted with both generalised linear models and generalised additive models for the geographical data. Average temperature, minimum temperature and wind speed were strongly correlated with disease incidence. The transmission of Zika during the 2016 epidemic appeared to decrease circulation of dengue in Cúcuta, an area of sustained high incidence of dengue. Socio-economic factors such as barriers to health and childhood services, inadequate sanitation and poor water supply suggested an unfavourable impact on the transmission of dengue, Zika and chikungunya in all three ecosystems. Socio-demographic influencers were also discussed including the influx of people to Cúcuta, fleeing political and economic instability from neighbouring Venezuela. Aedes aegypti is expanding its range and increasing the global threat of these diseases. It is therefore vital that we learn from the epidemiology of these arboviruses and translate it into an actionable local knowledge base. This is even more acute given the recent historical high of dengue cases in the Americas in 2019, preceding the COVID-19 pandemic, which is itself hampering mosquito control efforts.


Subject(s)
Chikungunya Fever/epidemiology , Dengue/epidemiology , Zika Virus Infection/epidemiology , Aedes/physiology , Aedes/virology , Animals , Chikungunya Fever/economics , Chikungunya Fever/virology , Chikungunya virus/physiology , Climate , Colombia/epidemiology , Dengue/economics , Dengue/virology , Dengue Virus/physiology , Economic Factors , Ecosystem , Humans , Mosquito Vectors/physiology , Mosquito Vectors/virology , South America , Temperature , Zika Virus/physiology , Zika Virus Infection/economics , Zika Virus Infection/virology
10.
Viruses ; 13(1)2020 12 29.
Article in English | MEDLINE | ID: covidwho-1004758

ABSTRACT

RNA viruses have gained plenty of attention during recent outbreaks of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and Ebola virus. ZIKV is a vector borne Flavivirus that is spread by mosquitoes and it mainly infects neuronal progenitor cells. One hallmark of congenital ZIKV disease is a reduced brain size in fetuses, leading to severe neurological defects. The World Health Organization (WHO) is urging the development of new antiviral treatments against ZIKV, as there are no efficient countermeasures against ZIKV disease. Previously, we presented a new class of host-targeting antivirals active against a number of pathogenic RNA viruses, such as SARS-CoV-2. Here, we show the transfer of the image-based phenotypic antiviral assay to ZIKV-infected brain cells, followed by mechanism-of-action studies and a proof-of-concept study in a three-dimensional (3D) organoid model. The novel antiviral compounds showed a therapeutic window against ZIKV in several cell models and rescued ZIKV-induced neurotoxicity in brain organoids. The compound's mechanism-of-action was pinpointed to late steps in the virus life cycle, impairing the formation of new virus particles. Collectively, in this study, we expand the antiviral activity of new small molecule inhibitors to a new virus class of Flaviviruses, but also uncover compounds' mechanism of action, which are important for the further development of antivirals.


Subject(s)
Antiviral Agents/pharmacology , Brain/metabolism , Organoids/metabolism , Zika Virus Infection/metabolism , Zika Virus/drug effects , Animals , Brain/pathology , COVID-19 , Cell Survival/drug effects , Humans , Organoids/pathology , RNA Viruses , Ribavirin/pharmacology , SARS-CoV-2 , Zika Virus/physiology , Zika Virus Infection/virology
12.
Cell Rep ; 33(5): 108339, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-898565

ABSTRACT

Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. In human corneal explants, blockade of IFNλR1 enhances replication of ZIKV and HSV-1 but not SARS-CoV-2. In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium.


Subject(s)
Betacoronavirus/physiology , Cornea/virology , Coronavirus Infections/transmission , Herpesvirus 1, Human/physiology , Interferons/immunology , Pneumonia, Viral/transmission , Zika Virus/physiology , Animals , Betacoronavirus/immunology , COVID-19 , Cornea/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Herpes Simplex/immunology , Herpes Simplex/transmission , Herpes Simplex/virology , Humans , Mice , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Replication/physiology , Zika Virus Infection/immunology , Zika Virus Infection/transmission , Zika Virus Infection/virology
13.
Am J Emerg Med ; 45: 154-155, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-848697

ABSTRACT

As the COVID-19 pandemic continues to progress, the medical community is rapidly trying to identify complications and patterns of disease to improve patient outcomes. In a recent systematic review, it has been reported that isolated cases of Guillain-Barre Syndrome (GBS) have occurred secondary to COVID-19 infection. GBS is defined as a rare, but potentially fatal, immune mediated disease of peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. While several cases of GBS secondary to COVID-19 infection have been reported in Italy, only one case has been reported in the United States (US). The reported case in the US was a 54- year old male. We present a case of GBS secondary to a COVID-19 infection and believe this to be the first documented female case in the US and the second documented case in the US overall. The presented case aims to supplement the existing body of knowledge and to assist clinicians in managing complications of COVID-19.


Subject(s)
COVID-19/epidemiology , Guillain-Barre Syndrome/epidemiology , Pandemics , SARS-CoV-2 , Zika Virus Infection/epidemiology , Aged , Comorbidity , Female , Humans , Incidence , United States/epidemiology , Zika Virus/isolation & purification , Zika Virus Infection/virology
14.
Int J Infect Dis ; 101: 191-193, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-799213

ABSTRACT

OBJECTIVES: We investigated seroreactivity by using a commercial SARS-CoV-2 ELISA test in samples collected from different groups of individuals, including patients diagnosed to have Dengue, Zika, and Chikungunya infection between 2015 and 2019, from an endemic area in the Caribbean Colombian region. METHODS: A total of 127 sera samples obtained from six different groups of individuals were included in this study: Group A: patients with confirmed SARS-CoV-2 infection; Group B: patients with symptoms suggestive of COVID-19 or asymptomatic contacts with confirmed patients; Group C: patients with acute or recent dengue virus infection; Group D: patients with acute Zika virus infection; Group E: patients with previous Chikungunya virus infection; and Group F: individuals with exposure to spotted fever group rickettsiae. RESULTS: Overall, group A, group B, and group D showed seroreactivity to SARS-CoV-2 in 92%, 75%, and 26% of samples, respectively; furthermore, group C, group E, and group F showed 100% seronegativity. CONCLUSIONS: We found 26% of serological cross-reactivity in patients with acute Zika virus infection by using a commercial SARS-CoV-2 ELISA test. Further studies are needed to evaluate whether serological cross-reaction is maintained with time in nonacute patients with previous exposure to the Zika virus and its effect in SARS-CoV-2 serosurveys in endemic areas for this arbovirus.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Cross Reactions , SARS-CoV-2/immunology , Zika Virus Infection/immunology , Zika Virus/immunology , Adolescent , Adult , Aged , Antibodies, Viral/blood , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Colombia/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Pandemics , Young Adult , Zika Virus Infection/blood , Zika Virus Infection/epidemiology , Zika Virus Infection/virology
15.
Sci Adv ; 6(39)2020 09.
Article in English | MEDLINE | ID: covidwho-796906

ABSTRACT

Detection of viruses is critical for controlling disease spread. Recent emerging viral threats, including Zika virus, Ebola virus, and SARS-CoV-2 responsible for coronavirus disease 2019 (COVID-19) highlight the cost and difficulty in responding rapidly. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches that mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show nonenzymatic detection of viral RNA with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with sample preparation using either RNA extraction or isothermal preamplification. Our assay requires minimal laboratory infrastructure and is adaptable to other viruses, as demonstrated by quickly developing DNA nanoswitches to detect SARS-CoV-2 RNA in saliva. Further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , DNA, Single-Stranded/genetics , Electrophoresis, Agar Gel/methods , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Sequence Analysis, RNA/methods , Base Sequence , COVID-19 , Cell Line, Tumor , Coronavirus Infections/virology , Dengue/diagnosis , Dengue/virology , Dengue Virus/genetics , Electrophoresis, Agar Gel/economics , Humans , Limit of Detection , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Saliva/virology , Sequence Analysis, RNA/economics , Zika Virus/genetics , Zika Virus Infection/diagnosis , Zika Virus Infection/virology
16.
J Exp Med ; 217(12)2020 12 07.
Article in English | MEDLINE | ID: covidwho-726090

ABSTRACT

Type I interferons (IFN-I) are a major antiviral defense and are critical for the activation of the adaptive immune system. However, early viral clearance by IFN-I could limit antigen availability, which could in turn impinge upon the priming of the adaptive immune system. In this study, we hypothesized that transient IFN-I blockade could increase antigen presentation after acute viral infection. To test this hypothesis, we infected mice with viruses coadministered with a single dose of IFN-I receptor-blocking antibody to induce a short-term blockade of the IFN-I pathway. This resulted in a transient "spike" in antigen levels, followed by rapid antigen clearance. Interestingly, short-term IFN-I blockade after coronavirus, flavivirus, rhabdovirus, or arenavirus infection induced a long-lasting enhancement of immunological memory that conferred improved protection upon subsequent reinfections. Short-term IFN-I blockade also improved the efficacy of viral vaccines. These findings demonstrate a novel mechanism by which IFN-I regulate immunological memory and provide insights for rational vaccine design.


Subject(s)
Immunogenicity, Vaccine/immunology , Interferon Type I/antagonists & inhibitors , Interferon-alpha/immunology , Receptor, Interferon alpha-beta/immunology , Viral Vaccines/immunology , Zika Virus Infection/immunology , Zika Virus/immunology , Animals , Antibodies, Blocking/immunology , Antibodies, Blocking/pharmacology , Antibodies, Viral/immunology , Antigen Presentation/immunology , CD8-Positive T-Lymphocytes/metabolism , Dendritic Cells/immunology , Disease Models, Animal , Gene Expression/immunology , HEK293 Cells , Humans , Immunologic Memory , Interferon-alpha/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Receptor, Interferon alpha-beta/genetics , Transfection , Zika Virus Infection/virology
17.
Viruses ; 12(7)2020 07 21.
Article in English | MEDLINE | ID: covidwho-670616

ABSTRACT

Arboviruses, including the Zika virus, have recently emerged as one of the most important threats to human health. The use of metagenomics-based approaches has already proven valuable to aid surveillance of arboviral infections, and the ability to reconstruct complete viral genomes from metatranscriptomics data is key to the development of new control strategies for these diseases. Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5'-UTR and 3'-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification.


Subject(s)
Arboviruses/genetics , Disease Outbreaks , Gene Expression Profiling/methods , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing/methods , Nidovirales/genetics , Zika Virus Infection/virology , Zika Virus/genetics , Humans , Mosquito Vectors/virology , Phylogeny , Polymerase Chain Reaction , Zika Virus Infection/epidemiology
18.
Trends Biotechnol ; 38(9): 943-947, 2020 09.
Article in English | MEDLINE | ID: covidwho-597298

ABSTRACT

Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5 years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.


Subject(s)
Coronavirus Infections/prevention & control , Drug Approval/organization & administration , Hemorrhagic Fever, Ebola/prevention & control , Influenza, Human/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/biosynthesis , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Ebola Vaccines/administration & dosage , Ebola Vaccines/biosynthesis , Ebolavirus/drug effects , Ebolavirus/immunology , Ebolavirus/pathogenicity , Europe/epidemiology , Global Health/trends , Government Regulation , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/virology , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/biosynthesis , Influenza, Human/epidemiology , Influenza, Human/immunology , Influenza, Human/virology , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/prevention & control , Severe Acute Respiratory Syndrome/virology , United States/epidemiology , Viral Vaccines/administration & dosage , Zika Virus/drug effects , Zika Virus/immunology , Zika Virus/pathogenicity , Zika Virus Infection/epidemiology , Zika Virus Infection/immunology , Zika Virus Infection/prevention & control , Zika Virus Infection/virology
19.
Virology ; 546: 88-97, 2020 07.
Article in English | MEDLINE | ID: covidwho-71808

ABSTRACT

The emergence and re-emergence of Zika virus (ZIKV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas worldwide. Despite these burdens, antiviral therapies do not exist, and inhibitors of ZIKV are therefore urgently needed. To elucidate the anti-ZIKV effect of lycorine, we used reverse transcription-quantitative real-time PCR (qRT-PCR), immunofluorescence, Westernwestern blot, and plaque forming assay to analyse viral RNA (vRNA), viral protein, progeny virus counts, and validated inhibitors in vitro using a variety of cell lines. Additionally, we found that lycorine acts post-infection according to time-of-addition assay, and inhibits RdRp activity. Lycorine protected AG6 mice against ZIKV-induced lethality by decreasing the viral load in the blood. Due to its potency and ability to target ZIKV infection in vivo and in vitro, lycorine might offer promising therapeutic possibilities for combatting ZIKV infections in the future.


Subject(s)
Amaryllidaceae Alkaloids/administration & dosage , Antiviral Agents/administration & dosage , Phenanthridines/administration & dosage , Zika Virus Infection/drug therapy , Zika Virus/drug effects , Amaryllidaceae Alkaloids/chemistry , Animals , Antiviral Agents/chemistry , Female , Humans , Male , Mice , Molecular Docking Simulation , Phenanthridines/chemistry , Virus Replication/drug effects , Zika Virus/genetics , Zika Virus/physiology , Zika Virus Infection/mortality , Zika Virus Infection/virology
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