Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| dengue virus ns proteins inhibit rig-i/mavs signaling by blocking tbk1/irf3 phosphorylation: dengue virus serotype 1 ns4a is a unique interferon-regulating virulence determinant. | dengue virus (denv) replication is inhibited by the prior addition of type i interferon or by rig-i agonists that elicit rig-i/mavs/tbk1/irf3-dependent protective responses. denv infection of primary human endothelial cells (ecs) results in a rapid increase in viral titer, which suggests that denv inhibits replication-restrictive rig-i/interferon beta (ifn-β) induction pathways within ecs. our findings demonstrate that denv serotype 4 (denv4) nonstructural (ns) proteins ns2a and ns4b inhibited r ... | 2015 | 25968648 |
| benzothiazole and pyrrolone flavivirus inhibitors targeting the viral helicase. | the flavivirus nonstructural protein 3 (ns3) is a protease and helicase, and on the basis of its similarity to its homologue encoded by the hepatitis c virus (hcv), the flavivirus ns3 might be a promising drug target. few flavivirus helicase inhibitors have been reported, in part, because few specific inhibitors have been identified when nucleic acid unwinding assays have been used to screen for helicase inhibitors. to explore the possibility that compounds inhibiting ns3-catalyzed atp hydrolysi ... | 0 | 26029739 |
| murine efficacy and pharmacokinetic evaluation of the flaviviral ns5 capping enzyme 2-thioxothiazolidin-4-one inhibitor bg-323. | arthropod-borne flavivirus infection continues to cause significant morbidity and mortality worldwide. identification of drug targets and novel antiflaviviral compounds to treat these diseases has become a global health imperative. a previous screen of 235,456 commercially available small molecules identified the 2-thioxothiazolidin-4-one family of compounds as inhibitors of the flaviviral ns5 capping enzyme, a promising target for antiviral drug development. rational drug design methodologies e ... | 2015 | 26075394 |
| nucleocytoplasmic transport of nucleocapsid proteins of enveloped rna viruses. | most viruses with non-segmented single stranded rna genomes complete their life cycle in the cytoplasm of infected cells. however, despite undergoing replication in the cytoplasm, the structural proteins of some of these rna viruses localize to the nucleus at specific times in the virus life cycle, primarily early in infection. limited evidence suggests that this enhances successful viral replication by interfering with or inhibiting the host antiviral response. nucleocapsid proteins of rna viru ... | 2015 | 26082769 |
| novel broad spectrum inhibitors targeting the flavivirus methyltransferase. | the flavivirus methyltransferase (mtase) is an essential enzyme that sequentially methylates the n7 and 2'-o positions of the viral rna cap, using s-adenosyl-l-methionine (sam) as a methyl donor. we report here that small molecule compounds, which putatively bind to the sam-binding site of flavivirus mtase and inhibit its function, were identified by using virtual screening. in vitro methylation experiments demonstrated significant mtase inhibition by 13 of these compounds, with the most potent ... | 2015 | 26098995 |
| differential utilisation of ceramide during replication of the flaviviruses west nile and dengue virus. | it is well established that +ssrna viruses manipulate cellular lipid homoeostasis and distribution to facilitate efficient replication. here, we show that the cellular lipid ceramide is redistributed to the west nile virus strain kunjin virus (wnvkun) replication complex (rc) but not to the dengue virus serotype 2 strain new guinea c (denvngc) rc. we show that prolonged chemical inhibition of serine palmitoyltransferase with myriocin had a significant deleterious effect on wnvkun replication but ... | 2015 | 26122470 |
| double-stranded rna is detected by immunofluorescence analysis in rna and dna virus infections, including those by negative-stranded rna viruses. | early biochemical studies of viral replication suggested that most viruses produce double-stranded rna (dsrna), which is essential for the induction of the host immune response. however, it was reported in 2006 that dsrna could be detected by immunofluorescence antibody staining in double-stranded dna and positive-strand rna virus infections but not in negative-strand rna virus infections. other reports in the literature seemed to support these observations. this suggested that negative-strand r ... | 2015 | 26136565 |
| the tortoise or the hare? impacts of within-host dynamics on transmission success of arthropod-borne viruses. | arthropod-borne viruses (arboviruses) are maintained in a cycle of alternating transmission between vertebrate hosts and arthropod vectors. arboviruses possess rna genomes capable of rapid diversification and adaptation, and the between-host trade-offs inherent to host alternation impose well-documented constraints on arbovirus evolution. here, we investigate the less well-studied within-host trade-offs that shape arbovirus replication dynamics and transmission. arboviruses generally establish l ... | 0 | 26150665 |
| understanding dengue virus capsid protein interaction with key biological targets. | dengue virus (denv) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. currently, there are no successful therapeutic or preventive approaches. we previously developed a peptide drug lead, pep14-23, that inhibits the biologically relevant interaction of denv capsid (c) protein with lipid droplets (lds). surprisingly, pep14-23 also inhibits denv c interaction with v ... | 2015 | 26161501 |
| amino terminal region of dengue virus ns4a cytosolic domain binds to highly curved liposomes. | dengue virus (denv) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. non-structural protein 4a (ns4a) is a vital component of the viral replication complex (rc) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. the n-terminal cytoplasmic region of ns4a(1-48) is known to preferentially interact with highly curved membranes. here, we provide experimental evidence for the stabl ... | 2015 | 26197333 |
| flavivirus rna synthesis in vitro. | establishment of in vitro systems to study mechanisms of rna synthesis for positive strand rna viruses have been very useful in the past and have shed light on the composition of protein and rna components, optimum conditions, the nature of the products formed, cis-acting rna elements and trans-acting protein factors required for efficient synthesis. in this review, we summarize our current understanding regarding the requirements for flavivirus rna synthesis in vitro. we describe details of rea ... | 2015 | 26272247 |
| flaviviral replication complex: coordination between rna synthesis and 5'-rna capping. | genome replication in flavivirus requires (-) strand rna synthesis, (+) strand rna synthesis, and 51-rna capping and methylation. to carry out viral genome replication, flavivirus assembles a replication complex, consisting of both viral and host proteins, on the cytoplasmic side of the endoplasmic reticulum (er) membrane. two major components of the replication complex are the viral non-structural (ns) proteins ns3 and ns5. together they possess all the enzymatic activities required for genome ... | 2015 | 26287232 |
| flavivirus sfrna suppresses antiviral rna interference in cultured cells and mosquitoes and directly interacts with the rnai machinery. | productive arbovirus infections require mechanisms to suppress or circumvent the cellular rna interference (rnai) pathway, a major antiviral response in mosquitoes. in this study, we demonstrate that two flaviviruses, dengue virus and kunjin virus, significantly repress sirna-mediated rnai in infected human cells as well as during infection of the mosquito vector culex quinquefasciatus. arthropod-borne flaviviruses generate a small structured non-coding rna from the viral 3' utr referred to as s ... | 2015 | 26331679 |
| interaction between flavivirus and cytoskeleton during virus replication. | flaviviruses are potentially human pathogens that cause major epidemics worldwide. flavivirus interacts with host cell factors to form a favourable virus replication site. cell cytoskeletons have been observed to have close contact with flaviviruses, which expands the understanding of cytoskeleton functions during virus replication, although many detailed mechanisms are still unclear. the interactions between the virus and host cytoskeletons such as actin filaments, microtubules, and intermediat ... | 2015 | 26347881 |
| ecuador paraiso escondido virus, a new flavivirus isolated from new world sand flies in ecuador, is the first representative of a novel clade in the genus flavivirus. | a new flavivirus, ecuador paraiso escondido virus (epev), named after the village where it was discovered, was isolated from sand flies (psathyromyia abonnenci, formerly lutzomyia abonnenci) that are unique to the new world. this represents the first sand fly-borne flavivirus identified in the new world. epev exhibited a typical flavivirus genome organization. nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. phylogenetic analysis o ... | 2015 | 26355096 |
| japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges. | to construct safer recombinant flavivirus vaccine, we exploited japanese encephalitis virus (jev) replicon-based platform to generate single-round infectious particles (srips) that expressed heterologous neutralizing epitope sp70 derived from enterovirus-71 (ev71). such pseudo-infectious virus particles, named srip-sp70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle. | 2015 | 26362772 |
| standing your ground to exoribonucleases: function of flavivirus long non-coding rnas. | members of the flaviviridae (e.g., dengue virus, west nile virus, and hepatitis c virus) contain a positive-sense rna genome that encodes a large polyprotein. it is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding rna. these non-coding rnas, which are called subgenomic flavivirus rnas (sfrnas) or xrn1-resistant rnas (xrrnas), are stable decay intermediates generated from the viral genomic rna through the stalling of the cellular exoribonuclease ... | 2015 | 26368052 |
| development and field evaluation of the sentinel mosquito arbovirus capture kit (smack). | although sentinel animals are used successfully throughout the world to monitor arbovirus activity, ethical considerations and cross-reactions in serological assays highlight the importance of developing viable alternatives. here we outline the development of a passive sentinel mosquito arbovirus capture kit (smack) that allows for the detection of arboviruses on honey-baited nucleic acid preservation cards (flinders technology associates; fta®) and has a similar trap efficacy as standard light ... | 2015 | 26444264 |
| new insights into control of arbovirus replication and spread by insect rna interference pathways. | arthropod-borne (arbo) viruses are transmitted by vectors, such as mosquitoes, to susceptible vertebrates. recent research has shown that arbovirus replication and spread in mosquitoes is not passively tolerated but induces host responses to control these pathogens. small rna-mediated host responses are key players among these antiviral immune strategies. studies into one such small rna-mediated antiviral response, the exogenous rna interference (rnai) pathway, have generated a wealth of informa ... | 2012 | 26466541 |
| ebolavirus vaccines: progress in the fight against ebola virus disease. | ebolaviruses are highly infectious pathogens that cause lethal ebola virus disease (evd) in humans and non-human primates (nhps). due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. in this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vacc ... | 2015 | 26535889 |
| dengue virus non-structural protein 1 modulates infectious particle production via interaction with the structural proteins. | non-structural protein 1 (ns1) is one of the most enigmatic proteins of the dengue virus (denv), playing distinct functions in immune evasion, pathogenesis and viral replication. the recently reported crystal structure of denv ns1 revealed its peculiar three-dimensional fold; however, detailed information on ns1 function at different steps of the viral replication cycle is still missing. by using the recently reported crystal structure, as well as amino acid sequence conservation, as a guide for ... | 2015 | 26562291 |
| defining hsp70 subnetworks in dengue virus replication reveals key vulnerability in flavivirus infection. | viral protein homeostasis depends entirely on the machinery of the infected cell. accordingly, viruses can illuminate the interplay between cellular proteostasis components and their distinct substrates. here, we define how the hsp70 chaperone network mediates the dengue virus life cycle. cytosolic hsp70 isoforms are required at distinct steps of the viral cycle, including entry, rna replication, and virion biogenesis. hsp70 function at each step is specified by nine distinct dnaj cofactors. of ... | 2015 | 26582131 |
| the molecular epidemiology and evolution of murray valley encephalitis virus: recent emergence of distinct sub-lineages of the dominant genotype 1. | recent increased activity of the mosquito-borne murray valley encephalitis virus (mvev) in australia has renewed concerns regarding its potential to spread and cause disease. | 2015 | 26600318 |
| analysis of the enzymatic activity of an ns3 helicase genotype 3a variant sequence obtained from a relapse patient. | the hepatitis c virus (hcv) is a species of diverse genotypes that infect over 170 million people worldwide, causing chronic inflammation, cirrhosis and hepatocellular carcinoma. hcv genotype 3a is common in brazil, and it is associated with a relatively poor response to current direct-acting antiviral therapies. the hcv ns3 protein cleaves part of the hcv polyprotein, and cellular antiviral proteins. it is therefore the target of several hcv drugs. in addition to its protease activity, ns3 is a ... | 2015 | 26658750 |
| alpha-synuclein expression restricts rna viral infections in the brain. | we have discovered that native, neuronal expression of alpha-synuclein (asyn) inhibits viral infection, injury, and disease in the central nervous system (cns). enveloped rna viruses, such as west nile virus (wnv), invade the cns and cause encephalitis, yet little is known about the innate neuron-specific inhibitors of viral infections in the cns. following wnv infection of primary neurons, we found that asyn protein expression is increased. the infectious titer of wnv and venezuelan equine ence ... | 2015 | 26719256 |
| identification and characterization of novel broad-spectrum inhibitors of the flavivirus methyltransferase. | flavivirus methyltransferase (mtase) is essential for viral replication. here we report the identification of small molecules through virtual screening that putatively bind to the sam-binding site of flavivirus mtase and inhibit its function. six of these computationally predicted binders were identified to show significant mtase inhibition with low micromolar inhibitory activity. the most active compounds showed broad-spectrum activity against the mtase proteins of other flaviviruses. two of th ... | 2015 | 26726314 |
| characterization of ryden (c19orf66) as an interferon-stimulated cellular inhibitor against dengue virus replication. | dengue virus (denv) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. however, no vaccine or specific antiviral is available for dengue. as seen in other rna viruses, the innate immune system plays a key role in controlling denv infection and disease outcome. although the interferon (ifn) response, which is central to host protective immunity, has been reported to limit denv replication, the molecular details of how denv infection is modulated ... | 2016 | 26735137 |
| chaperone-assisted protein folding is critical for yellow fever virus ns3/4a cleavage and replication. | dnajc14, a heat shock protein 40 (hsp40) cochaperone, assists with hsp70-mediated protein folding. overexpressed dnajc14 is targeted to sites of yellow fever virus (yfv) replication complex (rc) formation, where it interacts with viral nonstructural (ns) proteins and inhibits viral rna replication. how rcs are assembled and the roles of chaperones in this coordinated process are largely unknown. we hypothesized that chaperones are diverted from their normal cellular protein quality control funct ... | 2016 | 26739057 |
| acute flaccid paralysis: the new, the old, and the preventable. | acute flaccid paralysis (afp) has a changing epidemiology with ongoing polio outbreaks and emerging causes such as nonpolio enteroviruses and west nile virus (wnv). we report a case of afp from the horn of africa that was initially classified as probable polio but subsequently found to be due to wnv. | 2015 | 26788545 |
| lactimidomycin is a broad-spectrum inhibitor of dengue and other rna viruses. | dengue virus, a member of the flaviviridae family, is a mosquito-borne pathogen and the causative agent of dengue fever. despite the nearly 400 million new infections estimated annually, no vaccines or specific antiviral therapeutics are currently available. we identified lactimidomycin (ltm), a recently established inhibitor of translation elongation, as a potent inhibitor of dengue virus 2 infection in cell culture. the antiviral activity is observed at concentrations that do not affect cell v ... | 2016 | 26872864 |
| the e glycoprotein plays an essential role in the high pathogenicity of european-mediterranean is98 strain of west nile virus. | west nile virus (wnv) is the most widespread arbovirus in the world. several recent outbreaks and epizootics have been reported in europe and the mediterranean basin with increased virulence. in contrast to the well-characterized american and australian strains, little is known about the virulence determinants of the wnv european-mediterranean strains. to investigate the viral factors involved in the virulence of these strains, we generated chimeras between the highly neuropathogenic israel 1998 ... | 2016 | 26896935 |
| in vitro and in vivo evaluation of mutations in the ns region of lineage 2 west nile virus associated with neuroinvasiveness in a mammalian model. | west nile virus (wnv) strains may differ significantly in neuroinvasiveness in vertebrate hosts. in contrast to genetic lineage 1 wnvs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. a full-length infectious clone of a neurovirulent wnv lineage 2 strain (578/10; central europe) was generated and amino acid substitutions that have been shown to attenuate lineage 1 wnvs were introduced into the nonstructural proteins (ns1 (p250l), ns2a (a30p), ... | 2016 | 26907325 |
| comparative genomic analysis of pre-epidemic and epidemic zika virus strains for virological factors potentially associated with the rapidly expanding epidemic. | less than 20 sporadic cases of human zika virus (zikv) infection were reported in africa and asia before 2007, but large outbreaks involving up to 73% of the populations on the pacific islands have started since 2007, and spread to the americas in 2014. moreover, the clinical manifestation of zikv infection has apparently changed, as evident by increasing reports of neurological complications, such as guillain-barré syndrome in adults and congenital anomalies in neonates. we comprehensively comp ... | 2016 | 26980239 |
| reverse genetics approaches to control arenavirus. | several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. to date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. the development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell ... | 0 | 27076139 |
| suppression of kaposi's sarcoma-associated herpesvirus infection and replication by 5'-amp-activated protein kinase. | the host intracellular antiviral restriction factors inhibit viral infection and replication. the 5'-amp-activated protein kinase (ampk) is a cellular energy sensor regulating metabolic homeostasis. activated ampk inhibits the replication of numerous rna viruses but enhances the entry of vaccinia virus. however, the role of ampk in herpesvirus infection is unclear. in this study, we showed that the constitutive ampk activity restricted kaposi's sarcoma-associated herpesvirus (kshv) lytic replica ... | 2016 | 27147746 |
| dengue virus reporter replicon is a valuable tool for antiviral drug discovery and analysis of virus replication mechanisms. | dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (denv), a member of the flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. however, no specific antiviral drug or licensed vaccine currently targets denv infection. the replicon system has all the factors needed for viral replication in cells. since the development of replicon systems, transient and stable reporter replicon ... | 2016 | 27164125 |
| determinants of arbovirus vertical transmission in mosquitoes. | vertical transmission (vt) and horizontal transmission (ht) of pathogens refer to parental and non-parental chains of host-to-host transmission. combining ht with vt enlarges considerably the range of ecological conditions in which a pathogen can persist, but the factors governing the relative frequency of each transmission mode are poorly understood for pathogens with mixed-mode transmission. elucidating these factors is particularly important for understanding the epidemiology of arthropod-bor ... | 2016 | 27171170 |
| the crystal structure of zika virus helicase: basis for antiviral drug design. | 0 | 27172988 | |
| liposomal systems as nanocarriers for the antiviral agent ivermectin. | rna virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. the emergence and reemergence of rna viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others dengue, west nile virus, and yellow fever viruses. development of new and potent antivirals is thus urgently needed. ivermectin, an already known antihelminthic drug, has shown pot ... | 2016 | 27242902 |
| who regulates whom? an overview of rna granules and viral infections. | after viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mrna translation (protein synthesis) and the assembly of rna granules. two of these rna granules have been well characterized in yeast and mammalian cells, stress granules (sgs), which are translationally silent sites of rna triage and processing bodies (pbs), which are involved in mrna degradation. this review discusses the ... | 2016 | 27367717 |
| viral inhibition of the ifn-induced jak/stat signalling pathway: development of live attenuated vaccines by mutation of viral-encoded ifn-antagonists. | the interferon (ifn) induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection. the induction of the janus kinase/signal transducer and activation of transcription (jak/stat) signalling pathway by ifns leads to the upregulation of hundreds of interferon stimulated genes (isgs) for which, many have the ability to rapidly kill viruses within infected cells. during the long course of evolution, viruses have evolved an extraordinary range of ... | 2016 | 27367734 |
| west nile virus in europe and safety of blood transfusion. | west nile virus (wnv) has become an increasing issue in the transfusion setting since 2002, when it was firstly shown in the usa that it can be transmitted through blood transfusion. since then, several precautionary measures have been introduced in europe in order to reduce the possible risk of transmission via transfusion/solid organ transplantation. in addition, the epidemiological surveillance has been tightened and the network for communication of human wnv cases strengthened. this review w ... | 2016 | 27403087 |
| west nile virus temperature sensitivity and avian virulence are modulated by ns1-2b polymorphisms. | west nile virus (wnv) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. wnv strains isolated in north america, such as the prototype strain ny99, elicit a highly pathogenic response in certain avian species, notably american crows (amcrs; corvus brachyrhynchos). in contrast, a closely related strain, kn3829, isolated in kenya, exhibits a low viremic response with limited mortality in amcrs. previous work has associated the difference in pathogenicit ... | 2016 | 27548738 |
| development of 2, 7-diamino-1, 8-naphthyridine (danp) anchored hairpin primers for rt-pcr detection of chikungunya virus infection. | a molecular diagnostic platform with danp-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of chikungunya virus (chikv) with high sensitivity and specificity. the molecule 2, 7-diamino-1, 8-naphthyridine (danp) binds to a cytosine-bulge and emits fluorescence at 450 nm when it is excited by 400 nm light. thus, by measuring the decline in fluorescence emitted from danp-primer complexes after pcr reaction, we could monitor the pcr progress. by adapting ... | 2016 | 27571201 |
| vertical transmission of zika virus in aedes aegypti mosquitoes. | previous experimental studies have demonstrated that a number of mosquito-borne flavivirus pathogens are vertically transmitted in their insect vectors, providing a mechanism for these arboviruses to persist during adverse climatic conditions or in the absence of a susceptible vertebrate host. in this study, designed to test whether zika virus (zikv) could be vertically transmitted, female aedes aegypti and aedes albopictus were injected with zikv, and their f1 adult progeny were tested for zikv ... | 2016 | 27573623 |
| the golgi associated eri3 is a flavivirus host factor. | dengue virus (denv) is a mosquito-borne flavivirus classified into four serotypes (denv-1-4) that causes dengue fever (df), dengue hemorrhagic fever (dhf) or dengue shock syndrome (dss). an estimated 390 million people are at risk for infection with denv and there are no effective vaccines or therapeutics. we utilized rna chromatography coupled with quantitative mass spectrometry (qms) to identify host rna binding proteins (rbps) that interact with denv-2 rna. we identified eri3 (also prnpip and ... | 2016 | 27682269 |
| full genome sequence and sfrna interferon antagonist activity of zika virus from recife, brazil. | the outbreak of zika virus (zikv) in the americas has transformed a previously obscure mosquito-transmitted arbovirus of the flaviviridae family into a major public health concern. little is currently known about the evolution and biology of zikv and the factors that contribute to the associated pathogenesis. determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative proces ... | 2016 | 27706161 |
| molecular detection of flaviviruses and alphaviruses in mosquitoes (diptera: culicidae) from coastal ecosystems in the colombian caribbean. | arboviruses belonging to the genera flavivirus and alphavirus were detected in mosquitoes in a rural area of san bernardo del viento (córdoba, colombia). a total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. venezuelan equine encephalitis virus, dengue virus, west nile virus, st. louis encephalitis virus, yellow fever virus, and culex flavivirus were detected and identified by sequencing. the detection ... | 2016 | 27706377 |
| identification of a new broadly cross-reactive epitope within domain iii of the duck tembusu virus e protein. | in 2010, a pathogenic flavivirus termed duck tembusu virus (dtmuv) caused widespread outbreak of egg-drop syndrome in domesticated ducks in china. although the glycoprotein e of dtmuv is an important structural component of the virus, the b-cell epitopes of this protein remains uncharacterized. using phage display and mutagenesis, we identified a minimal b-cell epitope, (374)exe/dppfg(380), that mediates binding to a nonneutralizing monoclonal antibody. dtmuv-positive duck serum reacted with the ... | 2016 | 27824100 |
| invertebrate iridescent virus 6, a dna virus, stimulates a mammalian innate immune response through rig-i-like receptors. | insects are not only major vectors of mammalian viruses, but are also host to insect-restricted viruses that can potentially be transmitted to mammals. while mammalian innate immune responses to arboviruses are well studied, less is known about how mammalian cells respond to viruses that are restricted to infect only invertebrates. here we demonstrate that iiv-6, a dna virus of the family iridoviridae, is able to induce a type i interferon-dependent antiviral immune response in mammalian cells. ... | 2016 | 27824940 |
| replicon rna viral vectors as vaccines. | single-stranded rna viruses of both positive and negative polarity have been used as vectors for vaccine development. in this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. administration of replicon rna vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. immunization of mice, chicken, pigs and primates with virus-like particles, naked r ... | 2016 | 27827980 |
| yellow fever virus capsid protein is a potent suppressor of rna silencing that binds double-stranded rna. | mosquito-borne flaviviruses, including yellow fever virus (yfv), zika virus (zikv), and west nile virus (wnv), profoundly affect human health. the successful transmission of these viruses to a human host depends on the pathogen's ability to overcome a potentially sterilizing immune response in the vector mosquito. similar to other invertebrate animals and plants, the mosquito's rna silencing pathway comprises its primary antiviral defense. although a diverse range of plant and insect viruses has ... | 2016 | 27849599 |
| ebola vp40 in exosomes can cause immune cell dysfunction. | ebola virus (ebov) is an enveloped, ssrna virus from the family filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. the most recent outbreak of ebov in west africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. we have previously shown that exosomes from cells infected with hiv-1, htlv-1 and rift valley fever virus a ... | 2016 | 27872619 |
| virus variation resource - improved response to emergent viral outbreaks. | the virus variation resource is a value-added viral sequence data resource hosted by the national center for biotechnology information. the resource is located at http://www.ncbi.nlm.nih.gov/genome/viruses/variation/ and includes modules for seven viral groups: influenza virus, dengue virus, west nile virus, ebolavirus, mers coronavirus, rotavirus a and zika virus each module is supported by pipelines that scan newly released genbank records, annotate genes and proteins and parse sample descript ... | 2016 | 27899678 |
| archival isolates confirm a single topotype of west nile virus in australia. | west nile virus is globally wide-spread and causes significant disease in humans and animals. the evolution of west nile virus kunjin subtype in australia (wnvkun) was investigated using archival samples collected over a period of 50 years. based on the pattern of fixed amino acid substitutions and time-stamped molecular clock analyses, a single long-term lineage (or topotype) was inferred. this implies that a bottleneck exists such that regional strains eventually die out and are replaced with ... | 2016 | 27906966 |
| molecular mechanism of divalent-metal-induced activation of ns3 helicase and insights into zika virus inhibitor design. | zika virus has attracted increasing attention because of its potential for causing human neural disorders, including microcephaly in infants and guillain-barré syndrome. its ns3 helicase domain plays critical roles in ntp-dependent rna unwinding and translocation during viral replication. our structural analysis revealed a pre-activation state of ns3 helicase in complex with gtpγs, in which the triphosphate adopts a compact conformation in the absence of any divalent metal ions. in contrast, in ... | 2016 | 27915293 |
| ebolavirus diagnosis made simple, comparable and faster than molecular detection methods: preparing for the future. | the 2014/2015 ebolavirus outbreak resulted in more than 28,000 cases and 11,323 reported deaths, as of march 2016. domestic transmission of the guinea strain associated with the outbreak occurred mainly in six african countries, and international transmission was reported in four countries. outbreak management was limited by the inability to rapidly diagnose infected cases. a further fifteen countries in africa are predicted to be at risk of ebolavirus outbreaks in the future as a consequence of ... | 2018 | 29685158 |
| phospholipase a2 activity during the replication cycle of the flavivirus west nile virus. | positive-sense rna virus intracellular replication is intimately associated with membrane platforms that are derived from host organelles and comprised of distinct lipid composition. for flaviviruses, such as west nile virus strain kunjin virus (wnvkun) we have observed that these membrane platforms are derived from the endoplasmic reticulum and are rich in (at least) cholesterol. to extend these studies and identify the cellular lipids critical for wnvkun replication we utilized a whole cell li ... | 2018 | 29709018 |
| the distribution of important sero-complexes of flaviviruses in malaysia. | flaviviruses (fvs) are arthropod-borne viruses of medical and veterinary importance. numerous species of fvs have been isolated from various host; mainly humans, animals, ticks, and mosquitoes. certain fvs are extremely host-specific; at the same time, some fvs can infect an extensive range of species. based on published literatures, 11 species of fvs have been detected from diverse host species in malaysia. in humans, dengue virus and japanese encephalitis virus have been reported since 1901 an ... | 2019 | 30604332 |
| stability of west nile virus (flaviviridae: flavivirus) rna in mosquito excreta. | arbovirus surveillance is crucial for the implementation of vector-borne disease control measures. recently, it has been demonstrated that mosquitoes with a disseminated arbovirus infection excrete viral rna, which can be detected by molecular methods. thereby, mosquito excreta has been proposed as a sample type that could be utilized for arbovirus surveillance. in this study, we evaluated if west nile virus (kunjin strain, wnvkun) rna in culex annulirostris skuse (diptera: culicidae) excreta de ... | 2019 | 30937448 |
| arboviral diseases and malaria in australia, 2014–15: annual report of the national arbovirus and malaria advisory committee | this report describes the epidemiology of mosquito-borne diseases of public health importance in australia during the 2014–15 season (1 july 2014 to 30 june 2015) and includes data from human notifications, sentinel chicken, vector and virus surveillance programs. the national notifiable diseases surveillance system received notifications for 12,849 cases of disease transmitted by mosquitoes during the 2014–15 season. the australasian alphaviruses barmah forest virus and ross river virus account ... | 2019 | 30982295 |
| arbovirus surveillance using ftatm cards in modified co2 -baited encephalitis virus surveillance traps in the northern territory, australia. | in 2016, modified co2 -baited encephalitis virus surveillance (evs) traps were evaluated for flavivirus surveillance in the northern territory, australia. the traps were fitted with honey-soaked nucleic acid preservation cards (ftatm ) for mosquitoes to expectorate virus while feeding on the cards. cards were tested for the presence of selected arboviruses, with two cards testing positive for kunjin virus and alfuy, while sentinel chickens tested in parallel also showed kunjin virus activity at ... | 2019 | 31124223 |
| basimarols a, b, and c, highly oxygenated pimarane diterpenoids from basilicum polystachyon. | the highly oxygenated pimarane diterpenoids basimarols a, b, and c (3-5) were isolated from the plant species basilicum polystachyon, which was collected within the australian arid zone. structure elucidation was performed using a suite of spectroscopic techniques, including x-ray crystallography. anticancer and anti-denv activity of 3-5 was explored, but only limited activity was observed. more extensive antiviral evaluation of stachyonic acid a (1), which was also isolated from b. polystachyon ... | 2019 | 31553187 |
| inflammatory responses to a pathogenic west nile virus strain. | west nile virus (wnv) circulates across australia and was referred to historically as kunjin virus (wnvkun). wnvkun has been considered more benign than other wnv strains circulating globally. in 2011, a more virulent form of the virus emerged during an outbreak of equine arboviral disease in australia. | 2019 | 31664929 |
| antiviral activity of the fda-approved drug candesartan cilexetil against zika virus infection. | zika virus (zikv) is a mosquito-borne virus that has risen to prominence as a significant threat to public health in the recent decade. since its re-emergence in 2007, zikv has spread at an alarming rate and has since become endemic to multiple regions around the world. infections are primarily asymptomatic, however the virus has become associated with the development of severe neurological complications such as guillain-barré syndrome (gbs) and congenital microcephaly. at present, there are cur ... | 2019 | 31669333 |
| insulin potentiates jak/stat signaling to broadly inhibit flavivirus replication in insect vectors. | the world health organization estimates that more than half of the world's population is at risk for vector-borne diseases, including arboviruses. because many arboviruses are mosquito borne, investigation of the insect immune response will help identify targets to reduce the spread of arboviruses. here, we use a genetic screening approach to identify an insulin-like receptor as a component of the immune response to arboviral infection. we determine that vertebrate insulin reduces west nile viru ... | 2019 | 31722209 |
| flavivirus cross-reactivity to dengue nonstructural protein 1 antigen detection assays. | dengue virus (denv) and zika virus (zikv) are flaviviruses of public health relevance. both viruses circulate in the same endemic settings and acute infections generally manifest similar symptoms. this highlights the importance of accurate diagnosis for clinical management and outbreak control. one of the commonly used acute diagnostic markers for flaviviruses is nonstructural protein 1 (ns1). however, false positives due to antigenic cross-reactivity have been reported between denv and zikv inf ... | 2019 | 31878299 |