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mutations in nsp1 and pe2 are critical determinants of ross river virus-induced musculoskeletal inflammatory disease in a mouse model.the viral determinants of alphavirus-induced rheumatic disease have not been elucidated. we identified an rrv strain (dc5692) which, in contrast to the t48 strain, does not induce musculoskeletal inflammation in a mouse model of rrv disease. substitution of the rrv t48 strain nonstructural protein 1 (nsp1) coding sequence with that from strain dc5692 generated a virus that was attenuated in vivo despite similar viral loads in tissues. in contrast, substitution of the t48 pe2 coding region with t ...201021131014
a mouse model of chikungunya virus-induced musculoskeletal inflammatory disease: evidence of arthritis, tenosynovitis, myositis, and persistence.chikungunya virus (chikv), an emerging mosquito-borne alphavirus, causes debilitating rheumatic disease in humans that can last for weeks to months. starting in 2004, a chikv outbreak in the indian ocean region affected millions of people, and infected travelers introduced chikv to new regions. the pathogenesis of chikv is poorly understood, and no approved vaccines or specific therapies exist. a major challenge to the study of chikv disease is the lack of a small animal model that recapitulates ...201021224040
applications of animal models of infectious arthritis in drug discovery: a focus on alphaviral disease.animal models, which mimic human disease, are invaluable tools for understanding the mechanisms of disease pathogenesis and development of treatment strategies. in particular, animal models play important roles in the area of infectious arthritis. alphaviruses, including ross river virus (rrv), o'nyong-nyong virus, chikungunya virus (chikv), mayaro virus, semliki forest virus and sindbis virus, are globally distributed and cause transient illness characterized by fever, rash, myalgia, arthralgia ...201121366516
fatal human case of western equine encephalitis, uruguay.to the editor: the genus alphavirus (family togaviridae) comprises 29 viral species (1), grouped in at least 7 antigenic complexes by their serologic cross-reactivity (2). they are maintained in nature through enzootic cycles involving arthropods as vectors with subsequent amplification in small mammals or birds, and epizootic cycles between mosquitoes and large mammals such as horses or humans.201121529429
distribution of mosquitoes and mosquito-borne arboviruses in yunnan province near the china-myanmar-laos border.abstract. economic development and increased tourism in the southern region of yunnan province in china, adjacent to several countries in southeast asia, has increased the likelihood of import and export of vectors and vector-borne diseases. we report the results of surveillance of mosquitoes and mosquito-borne arboviruses along the border of china-myanmar-laos in 2005 and 2006, and information associating several arboviruses with infections and possibly disease in local human populations. seven ...201121540383
proteomic analysis of an aedes albopictus cell line infected with dengue serotypes 1 and 3 viruses.abstract: background: proteomic analysis was performed to identify proteins regulated during infection by dengue serotypes 1 and 3 in an aedes albopictus cell line. the potential of these viruses to cause severe disease at primary infection is of interest although few studies have been performed with these two dengue serotypes. results: the most relevant observation of our study is the significant overexpression of proteins involved in the cellular stress response and the glycolysis pathway afte ...201121767351
mayaro fever in the city of manaus, brazil, 2007-2008.abstract mayaro alphavirus is an arbovirus that causes outbreaks of acute febrile illness in the amazon region of south america. we show here the cases of mayaro fever that occurred in 2007-2008, in manaus, a large city and capital of the amazonas state, in western brazilian amazon. igm antibodies to mayaro virus (mayv) were detected by an enzyme immunoassay using infected cell cultures as antigen in the sera of 33 patients from both genera and 6-65 years old. mayv genome was also detected by ...201121923266
experimental transmission of mayaro virus by aedes aegypti.outbreaks of mayaro fever have been associated with a sylvatic cycle of mayaro virus (mayv) transmission in south america. to evaluate the potential for a common urban mosquito to transmit mayv, laboratory vector competence studies were performed with aedes aegypti from iquitos, peru. oral infection in ae. aegypti ranged from 0% (0/31) to 84% (31/37), with blood meal virus titers between 3.4 log(10) and 7.3 log(10) plaque-forming units (pfu)/ml. transmission of mayv by 70% (21/30) of infected mo ...201121976583
hunting in the rainforest and mayaro virus infection: an emerging alphavirus in ecuador.the objectives of this report were to document the potential presence of mayaro virus infection in ecuador and to examine potential risk factors for mayaro virus infection among the personnel of a military garrison in the amazonian rainforest.201122223990
ilheus virus infection in human, bolivia. 022377378
mayaro virus infection in traveler returning from amazon basin, northern peru. 201222469145
mitochondrial bioenergetic alterations in mouse neuroblastoma cells infected with sindbis virus: implications to viral replication and neuronal death.the metabolic resources crucial for viral replication are provided by the host. details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. in this work, respirometric analys ...201222485151
cell-based analysis of chikungunya virus e1 protein in membrane fusion.chikungunya fever is a pandemic disease caused by the mosquito-borne chikungunya virus (chikv). e1 glycoprotein mediation of viral membrane fusion during chikv infection is a crucial step in the release of viral genome into the host cytoplasm for replication. how the e1 structure determines membrane fusion and whether other chikv structural proteins participate in e1 fusion activity remain largely unexplored.201222520648
arthritogenic alphaviruses--an overview.mosquito-transmitted alphaviruses causing human rheumatic disease are globally distributed and include chikungunya virus, ross river virus, barmah forest virus, sindbis virus, o'nyong-nyong virus and mayaro virus. these viruses cause endemic disease and, occasionally, large epidemics; for instance, the 2004-2011 chikungunya epidemic resulted in 1.4-6.5 million cases, with imported cases reported in nearly 40 countries. the disease is usually self-limiting and characterized by acute and chronic s ...201222565316
adaptive changes in alphavirus mrna translation allowed colonization of vertebrate hosts.members of the alphavirus genus are arboviruses that alternate replication in mosquitoes and vertebrate hosts. in vertebrate cells, the alphavirus resists the activation of antiviral rna-activated protein kinase (pkr) by the presence of a prominent rna structure (downstream loop [dlp]) located in viral 26s transcripts, which allows an eif2-independent translation initiation of these mrnas. this article shows that dlp structure is essential for replication of sindbis virus (sinv) in vertebrate ce ...201222761388
genomic characterization of a novel virus of the family tymoviridae isolated from mosquitoes.the family tymoviridae comprises three plant virus genera, including tymovirus, marafivirus, and maculavirus, which are found in most parts of the world and cause severe agricultural losses. we describe a putatively novel member of the family tymoviridae, which is isolated from mosquitoes (culex spp.), referred to as cutlv.201222848363
genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus.chikungunya virus (chikv) and ross river virus (rrv) cause a debilitating, and often chronic, musculoskeletal inflammatory disease in humans. macrophages constitute the major inflammatory infiltrates in musculoskeletal tissues during these infections. however, the precise macrophage effector functions that affect the pathogenesis of arthritogenic alphaviruses have not been defined. we hypothesized that the severe damage to musculoskeletal tissues observed in rrv- or chikv-infected mice would pro ...201222972923
serological evidence of flaviviruses and alphaviruses in livestock and wildlife in trinidad.seroprevalence rates of selected arboviruses in animal populations in trinidad were determined using serum samples collected between 2006 and 2009 from horses (n=506), cattle (n=163), sheep (n=198), goats (n=82), pigs (n=184), birds (n=140), rodents (n=116), and other vertebrates (n=23). the sera were screened for antibodies to west nile virus (wnv), st. louis encephalitis virus (slev), ilheus virus (ilhv), bussuquara virus (bsqv), venezuelan equine encephalitis virus (veev), eastern equine ence ...201222989182
mayaro virus infection in amazonia: a multimodel inference approach to risk factor assessment.arboviral diseases are major global public health threats. yet, our understanding of infection risk factors is, with a few exceptions, considerably limited. a crucial shortcoming is the widespread use of analytical methods generally not suited for observational data--particularly null hypothesis-testing (nht) and step-wise regression (swr). using mayaro virus (mayv) as a case study, here we compare information theory-based multimodel inference (mmi) with conventional analyses for arboviral infec ...201223071852
pathogenic characterization of a cervical lymph node derived from a patient with kawasaki disease.kawasaki disease (kd) is the most common cause of multisystem vasculitis in childhood. although cervical lymphadenitis is one of the major symptoms in kd, lymph node biopsy is rarely performed, because kd is usually diagnosed by clinical symptoms. a cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with kd after the biopsy. the cervical lymph node specimen was analyzed with multivirus real-time pcr that can detect >160 vir ...201223071864
assessment of plaque assay methods for alphaviruses.viruses from the alphavirus genus are responsible for numerous arboviral diseases impacting human health throughout the world. confirmation of acute alphavirus infection is based on viral isolation, identification of viral rna, or a fourfold or greater increase in antibody titers between acute and convalescent samples. in convalescence, the specificity of antibodies to an alphavirus may be confirmed by plaque reduction neutralization test. to identify the best method for alphavirus and neutraliz ...201323085307
drivers, dynamics, and control of emerging vector-borne zoonotic diseases.emerging vector-borne diseases are an important issue in global health. many vector-borne pathogens have appeared in new regions in the past two decades, while many endemic diseases have increased in incidence. although introductions and emergence of endemic pathogens are often considered to be distinct processes, many endemic pathogens are actually spreading at a local scale coincident with habitat change. we draw attention to key differences between dynamics and disease burden that result from ...201223200503
[mayaro: a re-emerging arbovirus in venezuela and latin america].mayaro virus produces nonspecific, sublethal disease symptoms, often confused with dengue, but with symptoms of arthalgias that can cause incapacitating disability. outbreaks have been localized and sporadic in the pan-amazonia forest since its first isolation in 1954 (trinidad and tobago). the literature available is scarce, diverse and dispersed. mayaro virus is an alphavirus, phylogenetically related to the semliki forest antigenic complex. una and mayaro viruses are the only viruses of this ...201223242303
viruses acquired abroad: what does the primary care physician need to know?viral infections are imported by travelers and immigrants from tropical or subtropical regions. the primary care physician should be able to include these diseases in the differential diagnosis of various clinical conditions.201223264811
differential unfolded protein response during chikungunya and sindbis virus infection: chikv nsp4 suppresses eif2α phosphorylation.chikungunya (chikv) and sindbis (sinv) are arboviruses belonging to the alphavirus genus within the togaviridae family. they cause frequent epidemics of febrile illness and long-term arthralgic sequelae that affect millions of people each year. both viruses replicate prodigiously in infected patients and in vitro in mammalian cells, suggesting some level of control over the host cellular translational machinery that senses and appropriately directs the cell's fate through the unfolded protein re ...201323356742
factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease.many examples of the emergence or re-emergence of infectious diseases involve the adaptation of zoonotic viruses to new amplification hosts or to humans themselves. these include several instances of simple mutational adaptations, often to hosts closely related to the natural reservoirs. however, based on theoretical grounds, arthropod-borne viruses, or arboviruses, may face several challenges for adaptation to new hosts. here, we review recent findings regarding adaptive evolution of arboviruse ...023374123
global mapping of infectious disease.the primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. a systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. the results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all ...201323382431
a fully attenuated recombinant salmonid alphavirus becomes pathogenic through a single amino acid change in the e2 glycoprotein.a recombinant sleeping disease virus (rsdv) was previously shown to be totally attenuated and provide long-term protection in trout (c. moriette, m. leberre, a. lamoureux, t. l. lai, m. brémont, j. virol. 80:4088-4098, 2006). sequence comparison of the rsdv to wild-type genomes exhibited a number of nucleotide changes. in the current study, we demonstrate that the virulent phenotype of sdv was essentially associated with two amino acid changes, v8a and m136t, in the e2 glycoprotein, with the v8a ...201323449806
dendritic cell immunoreceptor regulates chikungunya virus pathogenesis in mice.chikungunya virus (chikv) is a mosquito-borne alphavirus responsible for recent epidemic outbreaks of debilitating disease in humans. alphaviruses are known to interact with members of the c-type lectin receptor family of pattern recognition proteins, and given that the dendritic cell immunoreceptor (dcir) is known to act as a negative regulator of the host inflammatory response and has previously been associated with rheumatoid arthritis, we evaluated dcir's role in response to chikv infection. ...201323487448
a tyrosine-to-histidine switch at position 18 of the ross river virus e2 glycoprotein is a determinant of virus fitness in disparate hosts.arthritogenic alphaviruses are human pathogens maintained in nature through alternating replication in vertebrates and mosquitoes. using chimeric viruses, we previously reported that replacement of the pe2 coding region of the t48 strain of ross river virus (rrv-t48) with that from the attenuated dc5692 strain, which differ by 7 amino acids, resulted in an attenuated disease phenotype in a mouse model of rrv-induced rheumatic disease. here, we demonstrate that introduction of one of these amino ...201323514884
interleukin-27 treated human macrophages induce the expression of novel micrornas which may mediate anti-viral properties.interleukin-27 (il-27) is a pleiotropic cytokine which plays important and diverse roles in the immune system. we have previously demonstrated that il-27 induces potent anti-viral effects against hiv-1, hiv-2, siv, hsv-2, kshv and influenza viruses in macrophages. this induction occurred in an interferon (ifn) independent manner and involved down regulation of sptbn1. micrornas (mirnas) are critical regulators of mrna translation and turnover. there have been reports that some mirnas inhibit vir ...201323535375
reemergence of chikungunya virus in indian subcontinent.chikungunya virus (chikv), a reemerging arboviral disease of public health concern is characterized by a triad of fever, rash and arthralgia. it was responsible for a number of epidemics in asia and africa. the severity of the current epidemic can be judged by the fact that an estimated 1.38 million people in india and one-third of the la reunion population (by april 2006) were affected by chikv. aedes aegypti and aedes albopictus are the major mosquitoes transmitting chikv in asia. various neur ...201023637474
performance of the tourniquet test for diagnosing dengue in peru.the tourniquet test (tt) is a physical examination maneuver often performed on patients suspected of having dengue. it has been incorporated into dengue diagnostic guidelines and is used in clinical studies. however, little is known about tt performance characteristics in different patient types or epidemiologic conditions. in the dengue-endemic city of iquitos, peru, we performed tts and dengue laboratory assays on 13,548 persons with febrile disease, recruited through either active (n = 1,095) ...201323716410
prolonged polyarthralgia in a german traveller with mayaro virus infection without inflammatory correlates.mayaro virus is endemic in south america and sporadic outbreaks have been described. it causes a dengue-like febrile illness accompanied by severe and long-lasting polyarthralgias. outside endemic regions, however, the disease is not well known and can be misdiagnosed as dengue. international travellers are at risk to acquire mayaro virus and due to increased worldwide travel infectious disease specialists need to be aware of such rare clinical entities.201323927600
molecular mechanisms involved in the pathogenesis of alphavirus-induced arthritis.arthritogenic alphaviruses, including ross river virus (rrv), chikungunya virus (chikv), sindbis virus (sinv), mayaro virus (mayv), o'nyong-nyong virus (onnv), and barmah forest virus (bfv), cause incapacitating and long lasting articular disease/myalgia. outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. this review discusses the molecular mechanisms involved in alphavirus-induced ...201324069610
identification of novel compounds inhibiting chikungunya virus-induced cell death by high throughput screening of a kinase inhibitor library.chikungunya virus (chikv) is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. the re-emergence of chikv has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. unfortunately, no effective treatment is currently available. the present study reports the use of resazurin in a cell-based high-throughput assay, and an i ...201324205414
mayaro virus infection, amazon basin region, peru, 2010-2013.during 2010-2013, we recruited 16 persons with confirmed mayaro virus infection in the peruvian amazon to prospectively follow clinical symptoms and serologic response over a 12-month period. mayaro virus infection caused long-term arthralgia in more than half, similar to reports of other arthritogenic alphaviruses.024210165
full inactivation of human influenza virus by high hydrostatic pressure preserves virus structure and membrane fusion while conferring protection to mice against infection.whole inactivated vaccines (wivs) possess greater immunogenicity than split or subunit vaccines, and recent studies have demonstrated that wivs with preserved fusogenic activity are more protective than non-fusogenic wivs. in this work, we describe the inactivation of human influenza virus x-31 by high hydrostatic pressure (hhp) and analyze the effects on the structure by spectroscopic measurements, light scattering, and electron microscopy. we also investigated the effects of hhp on the glycopr ...201324282553
a genome-wide analysis of rna pseudoknots that stimulate efficient -1 ribosomal frameshifting or readthrough in animal viruses.programmed -1 ribosomal frameshifting (prf) and stop codon readthrough are two translational recoding mechanisms utilized by some rna viruses to express their structural and enzymatic proteins at a defined ratio. efficient recoding usually requires an rna pseudoknot located several nucleotides downstream from the recoding site. to assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to d ...201324298557
attenuating mutations in nsp1 reveal tissue-specific mechanisms for control of ross river virus infection.ross river virus (rrv) is one of a group of mosquito-transmitted alphaviruses that cause debilitating, and often chronic, musculoskeletal disease in humans. previously, we reported that replacement of the nonstructural protein 1 (nsp1) gene of the mouse-virulent rrv strain t48 with that from the mouse-avirulent strain dc5692 generated a virus that was attenuated in a mouse model of disease. here we find that the six nsp1 nonsynonymous nucleotide differences between strains t48 and dc5692 are det ...201424429363
approaches to the treatment of disease induced by chikungunya virus.chikungunya virus, a re-emerging mosquito-borne alphavirus, causes fever, rash and persistent arthralgia/arthritis in humans. severe outbreaks have occurred resulting in infections of millions of people in southeast asia and africa. currently there are no antiviral drugs or vaccines for prevention and treatment of chikungunya infections. herein we report the current status of research on antiviral drugs and vaccines for chikungunya virus infections.024434329
occurrence and correlates of symptom persistence following acute dengue fever in peru.dengue virus (denv) infection causes an acute febrile illness generally considered to result in either complete recovery or death. some reviews describe persistent symptoms after the febrile phase, although empirical data supporting this phenomenon is scarce. we evaluated symptom persistence in acute febrile denv-infected and denv-negative (controls) individuals from peru. self-reported solicited symptoms were evaluated at an acute and a follow-up visit, occurring 10-60 days after symptom onset. ...201424470564
detection of arboviruses of public health interest in free-living new world primates (sapajus spp.; alouatta caraya) captured in mato grosso do sul, brazil.a sero-epidemiological survey was undertaken to detect the circulation of arboviruses in free-living non-human primates.201424474008
chikungunya fever in canada: fever and polyarthritis in a returned traveller. 201424566646
inhibition of mayaro virus infection by bovine lactoferrin.mayaro virus (mayv) is an arbovirus linked to several sporadic outbreaks of a highly debilitating febrile illness in many regions of south america. mayv is on the verge of urbanization from the amazon region and no effective antiviral intervention is available against human infections. our aim was to investigate whether bovine lactoferrin (blf), an iron-binding glycoprotein, could hinder mayv infection. we show that blf promotes a strong inhibition of virus infection with no cytotoxic effects. m ...201424606707
quercetin and quercetin 3-o-glycosides from bauhinia longifolia (bong.) steud. show anti-mayaro virus activity.the arthropod-borne mayaro virus (mayv) causes 'mayaro fever', a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical south america. recently, mayv has attracted attention due to its likely urbanization. currently, there are no licensed drugs against most mosquito-transmitted viruses. here, we investigated the in vitro anti-mayv activity of the flavonoids quercetin and its derivatives from the brazilian shrub bauhinia longifolia (b ...201424678592
ccr2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis.chikungunya virus (chikv) is a member of a globally distributed group of arthritogenic alphaviruses that cause weeks to months of debilitating polyarthritis/arthralgia, which is often poorly managed with current treatments. arthritic disease is usually characterized by high levels of the chemokine ccl2 and a prodigious monocyte/macrophage infiltrate. several inhibitors of ccl2 and its receptor ccr2 are in development and may find application for treatment of certain inflammatory conditions, incl ...201424696480
closing the gap between viral and noninfectious arthritis. 201424733902
persisting arthralgia due to mayaro virus infection in a traveler from brazil: is there a risk for attendants to the 2014 fifa world cup?the 2014 fifa world cup and the 2016 olympic games will attract large groups of visitors to brazil. these visitors will be at risk for different arboviral infections, some of which not well known outside endemic areas. we report a case of a 52-year-old dutch woman who presented with persistent arthralgia due to a mayaro virus (mayv) infection which she contracted in the amazon basin in brazil. mayv is a mosquito-borne alphavirus which primarily circulates in humid tropical forests of south ameri ...201424856445
genome analysis of mayaro virus imported to germany from french guiana. 024960052
clinical and virological descriptive study in the 2011 outbreak of dengue in the amazonas, brazil.dengue is a vector-borne disease in the tropical and subtropical region of the world and is transmitted by the mosquito aedes aegypti. in the state of amazonas, brazil during the 2011 outbreak of dengue all the four dengue virus (denv) serotypes circulating simultaneously were observed. the aim of the study was to describe the clinical epidemiology of dengue in manaus, the capital city of the state of the amazonas, where all the four denv serotypes were co-circulating simultaneously.201424978469
diagnosis of arboviruses using indirect sandwich igg elisa in horses from the brazilian amazon.the amazon as a whole is the largest reservoir of arboviruses worldwide, while the brazilian amazon hosts the largest variety of arboviruses isolated to date. in this study, the results of an indirect sandwich igg elisa, standardized for 19 arbovirustypes circulating among horses in brazilian amazon, were compared to results of the hemagglutination inhibition test. a screening test assessed the conditional probability distribution and a pearson linear correlation test determined the correlation ...201425013410
seroprevalence of alphavirus antibodies in a cross-sectional study in southwestern tanzania suggests endemic circulation of chikungunya.to date, alphavirus infections and their most prominent member, chikungunya fever, a viral disease which first became apparent in tanzania in 1953, have been very little investigated in regions without epidemic occurrence. few data exist on burden of disease and socio-economic and environmental covariates disposing to infection.201425079964
a novel live-attenuated vaccine candidate for mayaro fever.mayaro virus (mayv) is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of south america, and which has the potential to urbanize. because no specific treatment or vaccine is available for mayv infection, we capitalized on an ires-based approach to develop a live-attenuated mayv vaccine candidate. testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing anti ...201425101995
development of an algorithm for production of inactivated arbovirus antigens in cell culture.arboviruses are medically important pathogens that cause human disease ranging from a mild fever to encephalitis. laboratory diagnosis is essential to differentiate arbovirus infections from other pathogens with similar clinical manifestations. the arboviral diseases branch (adb) reference laboratory at the cdc division of vector-borne diseases (dvbd) produces reference antigens used in serological assays such as the virus-specific immunoglobulin m antibody-capture enzyme-linked immunosorbent as ...201425102428
molecular detection of mayaro virus during a dengue outbreak in the state of mato grosso, central-west brazil.mayaro virus (mayv) is frequently reported in pan-amazonia. the aim of this study was to investigate the circulation of alphaviruses during a dengue outbreak in the state of mato grosso, brazil. serum samples from dengue-suspected patients were subjected to multiplex semi-nested reverse transcriptase polymerase chain reaction for 11 flaviviruses and five alphaviruses, to nucleotide sequencing and to viral isolation. mayv was detected in 15 (2.5%) of 604 patients. twelve were co-infected with den ...201425141284
hepatitis a and e seroprevalence and associated risk factors: a community-based cross-sectional survey in rural amazonia.hepatitis a virus (hav) and hepatitis e virus (hev) are both transmitted by the faecal-oral route, and represent common causes of acute hepatitis in developing countries. the endemicity of hav infection has shifted from high to moderate in brazil. human cases of hev infection seem to be rare, although the virus has been detected in swine livestock and effluents of slaughterhouses. this study was to determine the epidemiology of hepatitis a and e in one of the largest agricultural settlements in ...201425149658
picornavirus morphogenesis.the picornaviridae represent a large family of small plus-strand rna viruses that cause a bewildering array of important human and animal diseases. morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and rna replication. although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this ...025184560
nmr study of non-structural proteins--part i: (1)h, (13)c, (15)n backbone and side-chain resonance assignment of macro domain from mayaro virus (mayv).macro domains are adp-ribose-binding modules present in all eukaryotic organisms, bacteria and archaea. they are also found in non-structural proteins of several positive strand rna viruses such as alphaviruses. here, we report the high yield expression and preliminary structural analysis through solution nmr spectroscopy of the macro domain from new world mayaro alphavirus. the recombinant protein was well-folded and in a monomeric state. an almost complete sequence-specific assignment of its ( ...201525217003
phospholipase a2 isolated from the venom of crotalus durissus terrificus inactivates dengue virus and other enveloped viruses by disrupting the viral envelope.the flaviviridae family includes several virus pathogens associated with human diseases worldwide. within this family, dengue virus is the most serious threat to public health, especially in tropical and sub-tropical regions of the world. currently, there are no vaccines or specific antiviral drugs against dengue virus or against most of the viruses of this family. therefore, the development of vaccines and the discovery of therapeutic compounds against the medically most important flaviviruses ...201425383618
evaluation of commercially available serologic diagnostic tests for chikungunya virus.chikungunya virus (chikv) is present or emerging in dengue virus-endemic areas. infections caused by these viruses share some common signs/symptoms, but prognosis, patient care, and persistent symptoms differ. thus, accurate diagnostic methods are essential for differentiating the infections. we evaluated 4 chikv serologic diagnostic tests, 2 of which showed poor sensitivity and specificity.025418184
chikungunya virus-vector interactions.chikungunya virus (chikv) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. since 2004, chikv has emerged in africa, indian ocean islands, asia, europe, and the americas, causing millions of human infections. central to understanding chikv emergence is knowledge of the natural ecology of transmission and vector infection dynamics. this review presents current understanding of chikv infection dynamics in mosquito v ...201425421891
anti-mayaro virus activity of cassia australis extracts (fabaceae, leguminosae).the arthropod-borne mayaro virus (mayv) causes 'mayaro fever', a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical south america. studies showed that the virus could also be transmitted by the mosquito aedes aegypti. recently, mayv has attracted attention due to its likely urbanization. to date, there are no drugs that can treat this illness.201425428163
evolutionary genetics and vector adaptation of recombinant viruses of the western equine encephalitis antigenic complex provides new insights into alphavirus diversity and host switching.western equine encephalitis virus (weev), highlands j virus (hjv), and fort morgan virus (fmv) are the sole representatives of the wee antigenic complex of the genus alphavirus, family togaviridae, that are endemic to north america. all three viruses have their ancestry in a recombination event involving eastern equine encephalitis virus (eeev) and a sindbis (sin)-like virus that gave rise to a chimeric alphavirus that subsequently diversified into the present-day weev, hjv, and fmv. here, we pr ...201425463613
multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.the recent epidemic of the arthritogenic alphavirus, chikungunya virus (chikv) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. herein we highlight the propensity of chikv infections to persist long term, both as persistent, steady-state, viraemias in multiple b cell deficient mouse strains, and as persistent rna (including negative-strand rna) in wild-type mice. the knockout mouse studies provided evid ...201425474568
isolation and characterization of mayaro virus from a human in acre, brazil.mayaro virus (mayv) is widely distributed throughout south america and is the etiologic agent of mayaro fever, an acute febrile illness often presenting with arthralgic manifestations. the true incidence of mayv infection is likely grossly underestimated because the symptomatic presentation is very similar to that of dengue fever and other acute febrile tropical diseases. we report the complete genome sequence of a mayv isolate detected from an acrelândia patient presenting with fever, chills, a ...201425510721
dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus and promotes viral replication leading to enhanced oncolysis in glioblastoma.targeting reprogrammed energy metabolism such as aerobic glycolysis is a potential strategy for cancer treatment. however, tumors exhibiting low-rate glycolysis or metabolic heterogeneity might be resistant to such treatment. we hypothesized that a therapeutic modality that drove cancer cells to high-rate glycolysis might sensitize cancer cells to interference directed against metabolic flux. in this study, we found that attenuated oncolytic measles virus edmonston strain (mv-edm) caused gliobla ...025575816
in- silico exploration of thirty alphavirus genomes for analysis of the simple sequence repeats.the compilation of simple sequence repeats (ssrs) in viruses and its analysis with reference to incidence, distribution and variation would be instrumental in understanding the functional and evolutionary aspects of repeat sequences. present study encompasses the analysis of ssrs across 30 species of alphaviruses. the full length genome sequences, assessed from ncbi were used for extraction and analysis of repeat sequences using imex software. the repeats of different motif sizes (mono- to penta ...201425606453
emerging alphaviruses in the americas: chikungunya and mayaro.chikungunya virus (chikv) and mayaro virus (mayv) are emergent arthropod-borne viruses that produce outbreaks of acute febrile illness with arthropathy. despite their different continental origins, chikv and mayv are closely related and are components of the semliki forest complex of the alphavirus (togaviridae). mayv and, more recently, chikv, which are both transmitted by aedes mosquitoes, have resulted in severe public health problems in the americas, including brazil. in this review, we pres ...201525626645
bovine lactoferrin inhibits toscana virus infection by binding to heparan sulphate.toscana virus is an emerging sandfly-borne bunyavirus in mediterranean europe responsible for neurological diseases in humans. it accounts for about 80% of paediatric meningitis cases during the summer. despite the important impact of toscana virus infection-associated disease on human health, currently approved vaccines or effective antiviral treatments are not available. in this research, we have analyzed the effect of bovine lactoferrin, a bi-globular iron-binding glycoprotein with potent ant ...201525643293
neutralising antibodies for mayaro virus in pantanal, brazil.the pantanal hosts diverse wildlife species and therefore is a hotspot for arbovirus studies in south america. a serosurvey for mayaro virus (mayv), eastern (eeev), western (weev) and venezuelan (veev) equine encephalitis viruses was conducted with 237 sheep, 87 free-ranging caimans and 748 equids, including 37 collected from a ranch where a neurologic disorder outbreak had been recently reported. sera were tested for specific viral antibodies using plaque-reduction neutralisation test. from a t ...201525650766
proteomics profiling of chikungunya-infected aedes albopictus c6/36 cells reveal important mosquito cell factors in virus replication.chikungunya virus (chikv) is the only causative agent of chikv fever with persistent arthralgia, and in some cases may lead to neurological complications which can be highly fatal, therefore it poses severe health issues in many parts of the world. chikv transmission can be mediated via the aedes albopictus mosquito; however, very little is currently known about the involvement of mosquito cellular factors during chikv-infection within the mosquito cells. unravelling the neglected aspects of mos ...201525738640
neutralising antibodies for mayaro virus in pantanal, brazil.the pantanal hosts diverse wildlife species and therefore is a hotspot for arbovirus studies in south america. a serosurvey for mayaro virus (mayv), eastern (eeev), western (weev) and venezuelan (veev) equine encephalitis viruses was conducted with 237 sheep, 87 free-ranging caimans and 748 equids, including 37 collected from a ranch where a neurologic disorder outbreak had been recently reported. sera were tested for specific viral antibodies using plaque-reduction neutralisation test. from a t ...201525742272
detection of mayaro virus infections during a dengue outbreak in mato grosso, brazil.arboviruses are common agents of human febrile illness worldwide. in dengue-endemic areas illness due to other arboviruses have been misdiagnosed as dengue based only on clinical-epidemiological data. in this study we investigated the presence of brazilian arboviruses in sera of 200 patients presenting acute febrile illness, during a dengue outbreak in sinop, mt, brazil. the results showed that 38 samples were positive to dengue virus (denv) type 1, two samples to denv type 4, and six to mayaro ...201525817238
new records of mosquitoes (diptera: culicidae) from bolívar state in south eastern venezuela, with 27 new species for the state and 5 of them new in the country.this is the first part of a series of studies related to mosquito ecological and biogeographic aspects. a total of 69 mosquito species (diptera: culicidae) was collected in 16 localities sampled in the gran sabana municipality, canaima national park, and venezuela. twenty-seven mosquito species are recorded for the first time from bolívar state, venezuela. five of them species are reported for the first time in venezuela: anopheles malefactor dyar and knab (1907); chagasia bonneae root (1927); c ...201525853113
false-negative dengue cases. 025923902
genetic diversity of venezuelan alphaviruses and circulation of a venezuelan equine encephalitis virus subtype iab strain during an interepizootic period.several species of alphaviruses have been previously described in the americas, some of which are associated with encephalitis and others are associated with arthralgia. venezuelan equine encephalitis virus (veev) and eastern equine encephalitis virus (eeev) are endemic to venezuela, with the former being responsible for major outbreaks of severe and often fatal disease in animals and humans. the aim of this study was to analyze the genetic diversity of venezuelan alphaviruses isolated during tw ...201525940191
emergence and potential for spread of chikungunya virus in brazil.in december 2013, an outbreak of chikungunya virus (chikv) caused by the asian genotype was notified in the caribbean. the outbreak has since spread to 38 regions in the americas. by september 2014, the first autochthonous chikv infections were confirmed in oiapoque, north brazil, and in feira de santana, northeast brazil.201525976325
mrna capping by venezuelan equine encephalitis virus nsp1: functional characterization and implications for antiviral research.alphaviruses are known to possess a unique viral mrna capping mechanism involving the viral nonstructural protein nsp1. this enzyme harbors methyltransferase (mtase) and nsp1 guanylylation (gt) activities catalyzing the transfer of the methyl group from s-adenosylmethionine (adomet) to the n7 position of a gtp molecule followed by the formation of an m(7)gmp-nsp1 adduct. subsequent transfer of m(7)gmp onto the 5' end of the viral mrna has not been demonstrated in vitro yet. here we report the bi ...201526041283
divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system.meningoencephalitis is one of the most common disorders of the central nervous system (cns) worldwide. viral meningoencephalitis differs from bacterial meningitis in several aspects. in some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. the knowledge of how mediators of inflammation can induce disease would contri ...201526286516
extended preclinical safety, efficacy and stability testing of a live-attenuated chikungunya vaccine candidate.we recently described a new, live-attenuated vaccine candidate for chikungunya (chik) fever, chikv/ires. this vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against chik virus (chikv) challenge of mice and nonhuman primates. to further evaluate its preclinical safety, we compared chikv/ires distribution and viral loads in interferon-α/β receptor-incompetent a129 mice to another chik vaccine candidate, 181/clone25, which proved highly immunogenic but mildly rea ...201526340754
syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance.arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. therefore, arbovirus infections are often neglected by travel diagnostics. here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers.201526372010
dengue virus ns1 protein modulates cellular energy metabolism by increasing glyceraldehyde-3-phosphate dehydrogenase activity.dengue is one of the main public health concerns worldwide. recent estimates indicate that over 390 million people are infected annually with the dengue virus (denv), resulting in thousands of deaths. among the denv nonstructural proteins, the ns1 protein is the only one whose function during replication is still unknown. ns1 is a 46- to 55-kda glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. despite its role in the pathogenic ...201526378175
evolutionary and ecological characterization of mayaro virus strains isolated during an outbreak, venezuela, 2010.in 2010, an outbreak of febrile illness with arthralgic manifestations was detected at la estación village, portuguesa state, venezuela. the etiologic agent was determined to be mayaro virus (mayv), a reemerging south american alphavirus. a total of 77 cases was reported and 19 were confirmed as seropositive. mayv was isolated from acute-phase serum samples from 6 symptomatic patients. we sequenced 27 complete genomes representing the full spectrum of mayv genetic diversity, which facilitated de ...026401714
zika virus outbreak, bahia, brazil. 026401719
peptide motif analysis predicts alphaviruses as triggers for rheumatoid arthritis.rheumatoid arthritis (ra) develops in response to both genetic and environmental factors. the strongest genetic determinant is hla-dr, where polymorphisms within the p4 and p6 binding pockets confer elevated risk. however, low disease concordance across monozygotic twin pairs underscores the importance of an environmental factor, probably infectious. the goal of this investigation was to predict the microorganism most likely to interact with hla-dr to trigger ra under the molecular mimicry hypot ...201526476978
utilization of an eilat virus-based chimera for serological detection of chikungunya infection.in december of 2013, chikungunya virus (chikv), an alphavirus in the family togaviridae, was introduced to the island of saint martin in the caribbean, resulting in the first autochthonous cases reported in the americas. as of january 2015, local and imported chikv has been reported in 50 american countries with over 1.1 million suspected cases. chikv causes a severe arthralgic disease for which there are no approved vaccines or therapeutics. furthermore, the lack of a commercially available, se ...201526492074
long-term arthralgia after mayaro virus infection correlates with sustained pro-inflammatory cytokine response.mayaro virus (mayv), an alphavirus similar to chikungunya virus (chikv), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. currently, the immune response and its role in the development of mayv-induced persistent arthralgia remain unknown. in this study, we evaluated the immune response of individuals with confirmed mayv infection in a one-year longitudinal study carried out in loreto, peru. we report that mayv ...201526496497
broadly neutralizing alphavirus antibodies bind an epitope on e2 and inhibit entry and egress.we screened a panel of mouse and human monoclonal antibodies (mabs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. passive transfer of broadly neutralizing mabs protected mice against infection by chikungunya, mayaro, and o'nyong'nyong alphaviruses. using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing mabs block multiple steps in the ...201526553503
sindbis and middelburg old world alphaviruses associated with neurologic disease in horses, south africa.old world alphaviruses were identified in 52 of 623 horses with febrile or neurologic disease in south africa. five of 8 sindbis virus infections were mild; 2 of 3 fatal cases involved co-infections. of 44 middelburg virus infections, 28 caused neurologic disease; 12 were fatal. middelburg virus likely has zoonotic potential.026583836
complete genome sequence of mayaro virus imported from the amazon basin to são paulo state, brazil.mayaro (mayv) is a neglected arbovirus from the tropical americas. here, we report the complete genome of an mayv isolate from a patient returning from the amazon basin and complaining of arthralgia, high fever, and headache, who was attended at an emergency service of são josé do rio preto, são paulo state, brazil.201526607884
complete genome sequence of mayaro virus (togaviridae, alphavirus) strain bear 20290 from brazil.we report here the complete genome sequence of mayaro virus strain bear 20290 isolated from haemagogus mosquitoes in 1960. the sequence presented here includes all nonstructural and structural proteins and the 5'- and 3'-untranslated (utr) regions.201526679574
global emergence of alphaviruses that cause arthritis in humans.arthropod-borne viruses (arboviruses) may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. these infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. it is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. presently, there is a great interest in the emergence ...201526689654
characterization of mitochondrial genome of haemagogus janthinomys (diptera: culicidae).haemagogus janthinomys is a mosquito of high importance in public health due its involvement on natural wild cycles of two important arboviruses in the brazilian amazon region: yellow fever virus (flaviviridae, flavivirus) and mayaro virus (togaviridae, alphavirus). here, we have sequenced and described all the mitochondrial genes for the hg. janthinomys species. the complete coding sequence is14 937 bp long and includes 37 functional genes, of which 13 codes for proteins, 22 for trna and 2 for ...201726709451
mayaro virus and dengue virus 1 and 4 natural infection in culicids from cuiabá, state of mato grosso, brazil.this study aimed to verify the diversity of culicidae species and their frequency of infection with flaviviruses and alphaviruses in cuiabá, state of mato grosso, brazil. mosquitoes were captured with nasci aspirators and hand net in 200 census tracts, identified alive at species level and pooled in one-20 (11,090 mosquitoes, 14 species). female pools (n = 610) were subjected to multiplex seminested-reverse transcription-polymerase chain reaction (rt-pcr) for 11 flavivirus and five alphavirus. p ...026784852
chikungunya: epidemiology.chikungunya virus is a mosquito-borne alphavirus that causes fever and debilitating joint pains in humans. joint pains may last months or years. it is vectored primarily by the tropical and sub-tropical mosquito, aedes aegypti, but is also found to be transmitted by aedes albopictus, a mosquito species that can also be found in more temperate climates. in recent years, the virus has risen from relative obscurity to become a global public health menace affecting millions of persons throughout the ...201626918158
a case of mayaro virus infection imported from french guiana.emergence of arboviruses is a rising problem in several areas in the world. here we report a case of mayaro virus infection that was diagnosed in a french citizen presenting a dengue-like syndrome with prolonged arthralgia following a travel in french guiana. diagnosis was based on serological testing, a newly developed specific rt-pcr and sequencing. the real incidence of this viral infection among travelers is poorly known but this case is the first reported in a european area where aedes albo ...201626921736
sustained elevated cytokine levels during recovery phase of mayaro virus infection. 026981875
an rna trapping mechanism in alphavirus mrna promotes ribosome stalling and translation initiation.during translation initiation, eukaryotic initiation factor 2 (eif2) delivers the met-trna to the 40s ribosomal subunit to locate the initiation codon (augi) of mrna during the scanning process. stress-induced eif2 phosphorylation leads to a general blockade of translation initiation and represents a key antiviral pathway in mammals. however, some viral mrnas can initiate translation in the presence of phosphorylated eif2 via stable rna stem-loop structures (dlp; downstream loop) located in thei ...201626984530
viral arthritis.acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. a viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. the epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. a travel history therefore forms an impo ...027037381
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