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1.
PLoS Pathog ; 16(2): e1008102, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027727

RESUMO

Understanding the circumstances under which arboviruses emerge is critical for the development of targeted control and prevention strategies. This is highlighted by the emergence of chikungunya and Zika viruses in the New World. However, to comprehensively understand the ways in which viruses emerge and persist, factors influencing reductions in virus activity must also be understood. Western equine encephalitis virus (WEEV), which declined during the late 20th century in apparent enzootic circulation as well as equine and human disease incidence, provides a unique case study on how reductions in virus activity can be understood by studying evolutionary trends and mechanisms. Previously, we showed using phylogenetics that during this period of decline, six amino acid residues appeared to be positively selected. To assess more directly the effect of these mutations, we utilized reverse genetics and competition fitness assays in the enzootic host and vector (house sparrows and Culex tarsalis mosquitoes). We observed that the mutations contemporary with reductions in WEEV circulation and disease that were non-conserved with respect to amino acid properties had a positive effect on enzootic fitness. We also assessed the effects of these mutations on virulence in the Syrian-Golden hamster model in relation to a general trend of increased virulence in older isolates. However, no change effect on virulence was observed based on these mutations. Thus, while WEEV apparently underwent positive selection for infection of enzootic hosts, residues associated with mammalian virulence were likely eliminated from the population by genetic drift or negative selection. These findings suggest that ecologic factors rather than fitness for natural transmission likely caused decreased levels of enzootic WEEV circulation during the late 20th century.

2.
Structure ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32049031

RESUMO

Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving structures such as the intraparticle polymerase complex because refinement can converge to an incorrect map and because the map could depict a nonrepresentative subset of particles or an average of heterogeneous particles. Using the nine-segmented Fako virus, we tested hypotheses for the arrangement and number of polymerase complexes within the virion by measuring how well each hypothesis describes the set of cryoelectron microscopy images of individual viral particles. We find that the polymerase complex in Fako virus binds at ten possible sites despite having only nine genome segments. A single asymmetric configuration describes the arrangement of these complexes in both virions and genome-free capsids. Similarities between the arrangements of Reoviridae with 9, 10, and 11 segments indicate the generalizability of this architecture.

3.
Viruses ; 12(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050663

RESUMO

In Senegal, chikungunya virus (CHIKV) is maintained in a sylvatic cycle and causes sporadic cases or small outbreaks in rural areas. However, little is known about the influence of the environment on its transmission. To address the question, 120 villages were randomly selected in the Kedougou region of southeastern Senegal. In each selected village, 10 persons by randomly selected household were sampled and tested for specific anti-CHIKV IgG antibodies by ELISA. We investigated the association of CHIKV seroprevalence with environmental variables using logistic regression analysis and the spatial correlation of village seroprevalence based on semivariogram analysis. Fifty-four percent (51%-57%) of individuals sampled during the survey tested positive for CHIKV-specific IgG. CHIKV seroprevalence was significantly higher in populations living close to forested areas (Normalized Difference Vegetation Index (NDVI), Odds Ratio (OR) = 1.90 (1.42-2.57)), and was negatively associated with population density (OR = 0.76 (0.69-0.84)). In contrast, in gold mining sites where population density was >400 people per km2, seroprevalence peaked significantly among adults (46% (27%-67%)) compared to all other individuals (20% (12%-31%)). However, traditional gold mining activities significantly modify the transmission dynamic of CHIKV, leading to a potential increase of the risk of human exposition in the region.

5.
Viruses ; 12(1)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936607

RESUMO

The risk of emergence and/or re-emergence of arthropod-borne viral (arboviral) infections is rapidly growing worldwide, particularly in Africa. The burden of arboviral infections and diseases is not well scrutinized because of the inefficient surveillance systems in endemic countries. Furthermore, the health systems are fully occupied by the burden of other co-existing febrile illnesses, especially malaria. In this review we summarize the epidemiology and risk factors associated with the major human arboviral diseases and highlight the gap in knowledge, research, and control in Sudan. Published data in English up to March 2019 were reviewed and are discussed to identify the risks and challenges for the control of arboviruses in the country. In addition, the lack of suitable diagnostic tools such as viral genome sequencing, and the urgent need for establishing a genomic database of the circulating viruses and potential sources of entry are discussed. Moreover, the research and healthcare gaps and global health threats are analyzed, and suggestions for developing strategic health policy for the prevention and control of arboviruses with focus on building the local diagnostic and research capacity and establishing an early warning surveillance system for the early detection and containment of arboviral epidemics are offered.

6.
Nat Microbiol ; 5(2): 232-233, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31992894
7.
Annu Rev Entomol ; 65: 313-332, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31594410

RESUMO

Chikungunya virus (CHIKV), a re-emerging mosquito-borne arbovirus, has caused millions of cases of severe, often chronic arthralgia during recent outbreaks. In Africa, circulation in sylvatic, enzootic cycles involves several species of arboreal mosquito vectors that transmit among diverse nonhuman primates and possibly other amplifying hosts. Most disease occurs when CHIKV emerges into a human-amplified cycle involving Aedes aegypti and sometimes Aedes albopictus transmission and extensive spread via travelers. Epidemiologic studies suggest that the transition from enzootic to epidemic cycles begins when people are infected via spillover in forests. However, efficient human amplification likely only ensues far from enzootic habitats where peridomestic vector and human densities are adequate. Recent outbreaks have been enhanced by mutations that adapt CHIKV for more efficient infection of Ae. albopictus, allowing for geographic expansion. However, epistatic interactions, sometimes resulting from founder effects following point-source human introductions, have profound effects on transmission efficiency, making CHIKV emergence somewhat unpredictable.

8.
Virus Res ; 275: 197802, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697989

RESUMO

An increasing number of insect-specific viruses are found around the world. Very recently, a new group of insect-specific viruses, the Mesoniviridae family, was discovered in Africa, Asia, North America and Australia. Here we report the first detection and isolation of a new virus belonging to Mesonivirus genus in Senegal, West Africa. The so-called Dianke virus was detected in 21 species of arthropods trapped in the eastern part of the country. Male individuals were also infected, supporting vertical transmission assertion of insect specific viruses. As described for other mesoniviruses, no viral replication was observed after inoculation of mammalian cells. Viral replication in mosquito cells was blocked at a temperature of 37 °C, highlighting the importance of thermal conditions in Mesonivirus host restriction. Similar to our study, where a diverse range of arthropod vectors were found infected by the new virus, several studies have detected mesonivirus infection in mosquitoes with concerns for human health. It has been shown that dual infections in mosquito can alter viral infectivity. Due to their extensive geographic distribution and host range, as well as their use as potential disease control agents in vector populations, more studies should be done for a better knowledge of arthropod-restricted viruses prevalence and diversity.

9.
Nat Commun ; 10(1): 5677, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831806

RESUMO

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3'UTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3'UTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3'UTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3'UTR-∆10-LAV may also be considered for maternal vaccination.

10.
Am J Trop Med Hyg ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31769391

RESUMO

In 2013, cases of chikungunya virus (CHIKV) infection were first detected in the Caribbean. Chikungunya virus rapidly spread through Central and South America, causing explosive outbreaks in naive populations. Since its emergence in 2004, the number of case and series reports describing severe, atypical manifestations seen in chikungunya patients has increased substantially, calling into question whether clinicians and health services are failing to diagnose these atypical cases because of not only insufficient knowledge but also limitations in the case classification. Although this classification based on the duration of the musculoskeletal (acute, subacute, and chronic forms) complaints helped guide therapeutic approaches directed to these manifestations, patients presenting severe or complicated forms, which are less frequent but produce most of the fatal outcomes, were not properly addressed. In Brazil and the Caribbean, a clear temporal and spatial association between excess overall mortality and the occurrence of chikungunya epidemics has been shown, supporting the hypothesis that many of these excess deaths were a consequence of CHIKV infections. Thus, accumulated experience has highlighted that the current chikungunya case classification does not encompass the actual needs presented by certain cases with atypical features nor does it contribute to early detection and management of potentially severe cases. With continued CHIKV circulation in three continents and recent reemergence in Asia and Europe, we need a classification that is prospective and informed both by initial clinical presentation and by progression of signs and symptoms.

11.
Int J Infect Dis ; 91: 38-43, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31704226

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of the Inbios (Seattle, US) and Euroimmun (Luebeck, Germany) chikungunya virus (CHIKV) IgM enzyme-linked immunoassays (ELISAs). METHODS: We evaluated the tests' accuracy on sera from 372 patients enrolled in an acute febrile illness surveillance study performed in Salvador, Brazil from Sept/2014 to Jul/2016, a period of simultaneous CHIKV, dengue (DENV), and Zika (ZIKV) virus transmission. We assessed the sensitivity on acute and paired convalescent sera from RT-PCR-confirmed CHIKV cases (collected at median one and 19 days post-onset of symptoms, respectively), and the specificity on sera of RT-PCR-confirmed DENV and ZIKV cases, and on negative patients. RESULTS: The Inbios and Euroimmun tests' sensitivities for acute samples were 4.0% and 10.3%, while for convalescent samples they were 92.4% and 96.9%, respectively. Overall, Inbios IgM ELISA specificities for acute and convalescent samples were 97.7% and 90.5%, respectively, and Euroimmun specificities were 88.5% and 83.9%, respectively. CONCLUSIONS: Both tests presented high sensitivity for convalescent samples. However, the Euroimmun test returned more equivocal results and presented a slightly lower specificity, which might result in a higher rate of false positives if the test is used in scenarios of low CHIKV transmission, when the chance of CHIKV infection is lower.

12.
J Am Mosq Control Assoc ; 35(3): 233-237, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31647710

RESUMO

South Texas is recognized as a potential area for the emergence and re-emergence of mosquito-borne diseases due to recent circulation of Zika, chikungunya, and dengue viruses. During 2017, high Aedes aegypti abundance found in the city of Brownsville, TX, in combination with the previous year's local transmission of Zika virus, triggered the activation of the Texas Department of State Health Services Emergency Mosquito Control Contingency Contract. A contract with the Clarke Environmental and Mosquito Control was a response to control Ae. aegypti, using a ground-based wide-area larvicide spray (WALS™) containing Bacillus thuringiensis israelensis. The WALS application was evaluated through a field-based bioassay and by comparing surveillance data pre- and post-WALS application. The WALS application bioassay demonstrated that the larvicide was effective up to 60 m into the target properties. Additionally, the number of Ae. aegypti captured in traps decreased in the WALS intervention areas compared with the untreated control areas, with an estimated 29% control.

13.
Viruses ; 11(9)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533267

RESUMO

The unprecedented outbreak of Zika virus (ZIKV) infection in the Americas from 2015 to 2017 prompted the publication of a large body of vector competence data in a relatively short period of time. Although differences in vector competence as a result of disparities in mosquito populations and viral strains are to be expected, the limited competence of many populations of the urban mosquito vector, Aedes aegypti, from the Americas (when its susceptibility is viewed relative to other circulating/reemerging mosquito-borne viruses such as dengue (DENV), yellow fever (YFV), and chikungunya viruses (CHIKV)) has proven a paradox for the field. This has been further complicated by the lack of standardization in the methodologies utilized in laboratory vector competence experiments, precluding meta-analyses of this large data set. As the calls for the standardization of such studies continue to grow in number, it is critical to examine the elements of vector competence experimental design. Herein, we review the various techniques and considerations intrinsic to vector competence studies, with respect to contemporary findings for ZIKV, as well as historical findings for other arboviruses, and discuss potential avenues of standardization going forward.

14.
Viruses ; 11(9)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480472

RESUMO

Licensure of a vaccine to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires use of the U.S. Food and Drug Administration (FDA) Animal Rule to assess vaccine efficacy as human studies are not feasible or ethical. An approach to selecting VEEV challenge strains for use under the Animal Rule was developed, taking into account Department of Defense (DOD) vaccine requirements, FDA Animal Rule guidelines, strain availability, and lessons learned from the generation of filovirus challenge agents within the Filovirus Animal Nonclinical Group (FANG). Initial down-selection to VEEV IAB and IC epizootic varieties was based on the DOD objective for vaccine protection in a bioterrorism event. The subsequent down-selection of VEEV IAB and IC isolates was based on isolate availability, origin, virulence, culture and animal passage history, known disease progression in animal models, relevancy to human disease, and ability to generate sufficient challenge material. Methods for the propagation of viral stocks (use of uncloned (wild-type), plaque-cloned, versus cDNA-cloned virus) to minimize variability in the potency of the resulting challenge materials were also reviewed. The presented processes for VEEV strain selection and the propagation of viral stocks may serve as a template for animal model development product testing under the Animal Rule to other viral vaccine programs. This manuscript is based on the culmination of work presented at the "Alphavirus Workshop" organized and hosted by the Joint Vaccine Acquisition Program (JVAP) on 15 December 2014 at Fort Detrick, Maryland, USA.

15.
Antiviral Res ; 171: 104596, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493417

RESUMO

Zika virus (ZIKV) has drawn global attention as the etiologic agent of Zika Congenital Syndrome in babies born to infected pregnant women. To prevent future ZIKV outbreaks and protect persons at risk for severe disease, we developed two live-attenuated vaccine (LAV) candidates containing 10- or 20-nucleotide deletions in the 3'UTR of the viral genome (Δ10 and Δ20). After a single-dose immunization, both Δ10 and Δ20 LAVs protected mice and non-human primates against ZIKV infection. Here, we characterized the stability, safety, and efficacy of the LAVs after continuously culturing them on manufacture Vero cells for ten rounds. Whole genome sequencing showed that passage 10 (P10) LAVs retained the engineered Δ10 and Δ20 deletions; one to four additional mutations emerged at different regions of the genome. In A129 mice, the P10 LAVs exhibited viremia higher than the un-passaged LAVs, but lower than wild-type ZIKV; unlike wild-type ZIKV-infected mice, none of the P10 LAV-infected mice developed disease or death, demonstrating that the P10 LAVs remained attenuated. Mice immunized with a single dose of the P10 LAVs developed robust neutralizing antibody titers (1/1,000 to 1/10,000) and were protected against epidemic ZIKV challenge. The P10 LAVs did not exhibit increased neurovirulence. Intracranial inoculation of one-day-old CD1 pups with 103 focus-forming units of the P10 Δ10 and Δ20 LAVs resulted in 100% and ≥80% survival, respectively. Furthermore, the P10 LAVs remained incompetent in infecting Aedes aegypti mosquitoes after intrathoracic microinjection. Our results support the phenotypic stability and further development of these promising LAVs for ZIKV.

16.
Nat Rev Microbiol ; 17(9): 569-586, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31213707

RESUMO

In the Anthropocene, in which we now live, climate change is impacting most life on Earth. Microorganisms support the existence of all higher trophic life forms. To understand how humans and other life forms on Earth (including those we are yet to discover) can withstand anthropogenic climate change, it is vital to incorporate knowledge of the microbial 'unseen majority'. We must learn not just how microorganisms affect climate change (including production and consumption of greenhouse gases) but also how they will be affected by climate change and other human activities. This Consensus Statement documents the central role and global importance of microorganisms in climate change biology. It also puts humanity on notice that the impact of climate change will depend heavily on responses of microorganisms, which are essential for achieving an environmentally sustainable future.

17.
J Infect Dis ; 220(5): 735-742, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31053842

RESUMO

BACKGROUND: Chikungunya virus (CHIKV) infection can result in chikungunya fever (CHIKF), a self-limited acute febrile illness that can progress to chronic arthralgic sequelae in a large percentage of patients. A new measles virus-vectored vaccine was developed to prevent CHIKF, and we tested it for immunogenicity and efficacy in a nonhuman primate model. METHODS: Nine cynomolgus macaques were immunized and boosted with the measles virus-vectored chikungunya vaccine or sham-vaccinated. Sera were taken at multiple times during the vaccination phase to assess antibody responses against CHIKV. Macaques were challenged with a dose of CHIKV previously shown to cause fever and viremia, and core body temperature, viremia, and blood cell and chemistry panels were monitored. RESULTS: The vaccine was well tolerated in all macaques, and all seroconverted (high neutralizing antibody [PRNT80 titers, 40-640] and enzyme-linked immunosorbent assay titers) after the boost. Furthermore, the vaccinated primates were protected against viremia, fever, elevated white blood cell counts, and CHIKF-associated cytokine changes after challenge with the virulent La Reunión CHIKV strain. CONCLUSIONS: These results further document the immunogenicity and efficacy of a measles-vectored chikungunya vaccine that shows promise in Phase I-II clinical trials. These findings are critical to human health because no vaccine to combat CHIKF is yet licensed.

18.
Vaccine ; 37(24): 3146-3150, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31047675

RESUMO

Over the past decade, chikungunya virus (CHIKV) has emerged as a major cause of mosquito-borne disease with transmission reported in over 100 countries worldwide. Although several strategies have been pursued for the development of a CHIKV vaccine, none has been approved yet. In this study, we describe the development of several vaccine vectors that express the structural proteins of the La Réunion CHIKV strain LR2006-OPY1. Protection from virus-induced pathologic changes was observed in vaccinated C57BL/6 mice, an important model for CHIKV vaccine development because of their ability to recapitulate several signs shown in infected humans. This study uniquely demonstrates the capacity of a mucosally-administered adenovirus vaccine to induce serum antibody responses and confer protective efficacy in a pre-clinical model. Our data provide further evidence in support of the clinical development of this oral Ad-CHIKV vaccine strategy in populations at high risk of contracting the disease.

19.
Viruses ; 11(5)2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31130629

RESUMO

Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and for some viruses, by the ultrastructural cytopathic effects and/or specific structures forming in the host cell during their replication. Ultrastructural characteristics are usually sufficient for the identification of a virus to the family level. In this review, we summarize 25 years of experience in identification of novel viruses from the collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA).

20.
J Med Primatol ; 48(4): 257-259, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30945306

RESUMO

A cynomolgus macaque (Macaca fascicularis) with a pre-existing, undiagnosed, subclinical but severe cerebral hydrocephalus was enrolled in a study of long-term immunogenicity of the IRES/CHIK vaccine. The animal began showing signs of neurological dysfunction post-vaccination, which progressed and ultimately resulted in euthanasia. The underlying brain abnormality was revealed at necropsy and was subsequently investigated with gross and microscopic examination. This becomes the first reported case of an adverse event following administration of a live attenuated vaccine and suggests the possibility of an increased susceptibility risk of unwanted adverse outcome associated with vaccination in populations with pre-existing conditions such as hydrocephalus.

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