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1.
Pediatr Pulmonol ; 55(5): 1237-1245, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32176838

RESUMO

Respiratory syncytial virus (RSV) is an important cause of early life acute respiratory infections. Potentially pathogenic respiratory bacteria, including Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are frequently detected during RSV infections and associated with increased illness severity. However, the temporal dynamics of bacterial colonization associated with RSV infection remain unclear. We used weekly nasal swab data from a prospective longitudinal birth cohort in Brisbane, Australia, to investigate bacterial colonization patterns within children aged less than 2 years in the 4-week period before and after an RSV infection. During 54 RSV infection episodes recorded in 47 children, both S. pneumoniae and M. catarrhalis were detected frequently (in 33 [61.1%] and 26 [48.1%] RSV infections, respectively). In most cases, S. pneumoniae and M. catarrhalis colonization preceded the viral infection, with the nasal load of each increasing during RSV infection. Generally, the dominant serotype of S. pneumoniae remained consistent in the 1 to 2 weeks immediately before and after RSV infection. Little evidence was found to indicate that prior colonization with either bacteria predisposed participants to developing RSV infection during the annual seasonal epidemic. Possible coacquisition events, where the bacteria species was first detected with RSV and not in the preceding 4 weeks, were observed in approximately 20% of RSV/S. pneumoniae and RSV/M. catarrhalis codetections. Taken together our results indicate that RSV generally triggered an outgrowth, rather than a new acquisition, of S. pneumoniae and M. catarrhalis from the resident microbial community.

2.
Anal Chim Acta ; 1107: 85-91, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32200905

RESUMO

We report a flow-cytometry based method capable of detecting a range of analytes by monitoring the analyte-induced clustering of magnetic and fluorescent nanoparticles with flow cytometry. Using the dengue viral antigen (NS1) as an example, antibodies were conjugated to magnetic and fluorescent nanoparticles in a sandwich immunoassay format. These nanoparticles formed clusters when NS1 was present in a sample and the cluster formation was directly proportional to the concentration of antigen. Simultaneous flow cytometry measurement of cluster size, as detected by the forward scatter channel, combined with fluorescence intensity led to a reduction in the assay background signal, resulting in improved analytical sensitivity. We were able to detect 2.5 ng mL-1 of NS1 in serum samples by quantifying the clusters, a two-log fold improvement in the assay limit of detection over total fluorescence quantification alone.

3.
Microbiology ; 166(1): 63-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714201

RESUMO

Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are frequently co-associated during acute respiratory infections, particularly amongst infants and young children. In this study, we aimed to identify strains of RSV and serotypes/sequence types of S. pneumoniae associated with co-infections within a cohort of paediatric patients, and to assess RSV-mediated adhesion of pneumococcal isolates. The RSV glycoprotein sequence was determined for 58 RSV-positive samples and molecular serotyping and MLST was used to analyse 26 pneumococcal isolates. We also compared 23 pneumococcal isolates for their adherence to RSV-infected or mock-infected airway epithelia cells using immunofluorescence microscopy and automated particle counting. The tight association between RSV and S. pneumoniae was also visualized using scanning electron microscopy. This study did not identify any statistically significant trend in the strains of RSV and S. pneumoniae associated with co-infections. Furthermore, almost all isolates (22 of 23) showed significantly increased adherence to RSV-infected cells. The level of adherence did not appear to correlate with pneumococcal strain or sequence type, and isolates obtained from RSV-infected patients displayed a similar level of adherence as those from RSV-negative patients. The absence of particular S. pneumoniae or RSV strains associated with co-infection, together with the near ubiquitous presence of RSV-mediated adhesion throughout the pneumococcal clinical isolates, may indicate that the mechanisms governing the association with RSV are of sufficient importance to be maintained across much of the species.

4.
PLoS Pathog ; 15(12): e1008218, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31790509

RESUMO

Dengue virus (DENV) transmission by mosquitoes is a time-dependent process that begins with the consumption of an infectious blood-meal. DENV infection then proceeds stepwise through the mosquito from the midgut to the carcass, and ultimately to the salivary glands, where it is secreted into saliva and then transmitted anew on a subsequent bite. We examined viral kinetics in tissues of the Aedes aegypti mosquito over a finely graded time course, and as per previous studies, found that initial viral dose and serotype strain diversity control infectivity. We also found that a threshold level of virus is required to establish body-wide infections and that replication kinetics in the early and intermediate tissues do not predict those of the salivary glands. Our findings have implications for mosquito GMO design, modeling the contribution of transmission to vector competence and the role of mosquito kinetics in the overall DENV epidemiological landscape.


Assuntos
Vírus da Dengue , Dengue/virologia , Interações Hospedeiro-Parasita/fisiologia , Mosquitos Vetores/virologia , Aedes , Animais , Cinética , Replicação Viral
5.
Sci Transl Med ; 11(522)2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31826984

RESUMO

Flaviviruses such as dengue, yellow fever, Zika, West Nile, and Japanese encephalitis virus present substantial global health burdens. New vaccines are being sought to address safety and manufacturing issues associated with current live attenuated vaccines. Here, we describe a new insect-specific flavivirus, Binjari virus, which was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of the aforementioned pathogenic vertebrate-infecting flaviviruses (VIFs). Chimeric BinJ/VIF-prME viruses remained replication defective in vertebrate cells but replicated with high efficiency in mosquito cells. Cryo-electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental VIFs. Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 109.5 cell culture infectious dose/ml or ≈7 mg/liter. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR-/- mouse models). BinJ/VIF-prME viruses thus represent a versatile, noninfectious (for vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.

6.
Vaccines (Basel) ; 7(4)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31756967

RESUMO

Dengue virus is the most important arbovirus impacting global human health, with an estimated 390 million infections annually, and over half the world's population at risk of infection. While significant efforts have been made to develop effective vaccines to mitigate this threat, the task has proven extremely challenging, with new approaches continually being sought. The majority of protective, neutralizing antibodies induced during infection are targeted by the envelope (E) protein, making it an ideal candidate for a subunit vaccine approach. Using truncated, recombinant, secreted E proteins (sE) of all 4 dengue virus serotypes, we have assessed their immunogenicity and protective efficacy in mice, with or without Quil-A as an adjuvant, and delivered via micropatch array (MPA) to the skin in comparison with more traditional routes of immunization. The micropatch contains an ultra-high density array (21,000/cm2) of 110 µm microprojections. Mice received 3 doses of 1 µg (nanopatch, intradermal, subcutaneous, or intra muscular injection) or 10 µg (intradermal, subcutaneous, or intra muscular injection) of tetravalent sE spaced 4 weeks apart. When adjuvanted with Quil-A, tetravalent sE vaccination delivered via MPA resulted in earlier induction of virus-neutralizing IgG antibodies for all four serotypes when compared with all of the other vaccination routes. Using the infectious dengue virus AG129 mouse infectious dengue model, these neutralizing antibodies protected all mice from lethal dengue virus type 2 D220 challenge, with protected animals showing no signs of disease or circulating virus. If these results can be translated to humans, MPA-delivered sE represents a promising approach to dengue virus vaccination.

7.
J Nat Prod ; 82(10): 2828-2834, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553187

RESUMO

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, revealed broad spectrum antiviral activity against West Nile virus (Kunjin strain, WNVKun) and human influenza viruses H1N1 and H3N2.

8.
PLoS One ; 14(7): e0218936, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31260467

RESUMO

INTRODUCTION: HIV misdiagnosis leads to severe individual and public health consequences. Retesting for verification of all HIV-positive cases prior to antiretroviral therapy initiation can reduce HIV misdiagnosis, yet this practice has not been not widely implemented. METHODS: We evaluated and compared the cost of retesting for verification of HIV seropositivity (retesting) to the cost of antiretroviral treatment (ART) for misdiagnosed cases in the absence of retesting (no retesting), from the perspective of the health care system. We estimated the number of misdiagnosed cases based on a review of misdiagnosis rates, and the number of positives persons needing ART initiation by 2020. We presented the total and per person costs of retesting as compared to no retesting, over a ten-year horizon, across 50 countries in Africa grouped by income level. We conducted univariate sensitivity analysis on all model input parameters, and threshold analysis to evaluate the parameter values where the total costs of retesting and the costs no retesting are equivalent. Cost data were adjusted to 2017 United States Dollars. RESULTS AND DISCUSSION: The estimated number of misdiagnoses, in the absence of retesting was 156,117, 52,720 and 29,884 for lower-income countries (LICs), lower-middle income countries (LMICs), and upper middle-income countries (UMICs), respectively, totaling 240,463 for Africa. Under the retesting scenario, costs per person initially diagnosed were: $40, $21, and $42, for LICs, LMICs, and UMICs, respectively. When retesting for verification is implemented, the savings in unnecessary ART were $125, $43, and $75 per person initially diagnosed, for LICs, LMICs, and UMICs, respectively. Over the ten-year horizon, the total costs under the retesting scenario, over all country income levels, was $475 million, and was $1.192 billion under the no retesting scenario, representing total estimated savings of $717 million in HIV treatment costs averted. CONCLUSIONS: Results show that to reduce HIV misdiagnosis, countries in Africa should implement the WHO's recommendation of retesting for verification prior to ART initiation, as part of a comprehensive quality assurance program for HIV testing services.


Assuntos
Sorodiagnóstico da AIDS/economia , Fármacos Anti-HIV/economia , Terapia Antirretroviral de Alta Atividade/economia , Análise Custo-Benefício , Infecções por HIV/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , África/epidemiologia , Países em Desenvolvimento , Erros de Diagnóstico , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Renda/estatística & dados numéricos , Masculino
9.
Mayo Clin Proc ; 94(9): 1834-1839, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235278

RESUMO

Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination.


Assuntos
Comunicação , Vírus do Sarampo/imunologia , Sarampo/epidemiologia , Sarampo/prevenção & controle , Terapia Viral Oncolítica/métodos , Vacinação/efeitos adversos , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/organização & administração , Europa (Continente) , Feminino , Humanos , Masculino , Prevalência , Medição de Risco , Estados Unidos , Vacinação/métodos
10.
Virus Evol ; 5(1): vez012, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31191980

RESUMO

Wolbachia is an intracellular endosymbiont of insects that inhibits the replication of a range of pathogens in its arthropod hosts. The release of Wolbachia into wild populations of mosquitoes is an innovative biocontrol effort to suppress the transmission of arthropod-borne viruses (arboviruses) to humans, most notably dengue virus. The success of the Wolbachia-based approach hinges upon the stable persistence of the 'pathogen blocking' effect, whose mechanistic basis is poorly understood. Evidence suggests that Wolbachia may affect viral replication via a combination of competition for host resources and activation of host immunity. The evolution of resistance against Wolbachia and pathogen blocking in the mosquito or the virus could reduce the public health impact of the symbiont releases. Here, we investigate if dengue 3 virus (DENV-3) is capable of accumulating adaptive mutations that improve its replicative capacity during serial passage in Wolbachia wMel-infected cells. During the passaging regime, viral isolates in Wolbachia-infected cells exhibited greater variation in viral loads compared to controls. The viral loads of these isolates declined rapidly during passaging due to the blocking effects of Wolbachia carriage, with several being lost all together and the remainder recovering to low but stable levels. We attempted to sequence the genomes of the surviving passaged isolates but, given their low abundance, were unable to obtain sufficient depth of coverage for evolutionary analysis. In contrast, viral loads in Wolbachia-free control cells were consistently high during passaging. The surviving isolates passaged in the presence of Wolbachia exhibited a reduced ability to replicate even in Wolbachia-free cells. These experiments demonstrate the challenge for dengue in evolving resistance to Wolbachia-mediated blocking.

11.
Transfusion ; 59(7): 2223-2227, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31050821

RESUMO

BACKGROUND: Yellow fever virus (YFV) is endemic to tropical and subtropical areas in South America and Africa, and is currently a major public health threat in Brazil. Transfusion transmission of the yellow fever vaccine virus has been demonstrated, which is indicative of the potential for viral transfusion transmission. An approach to manage the potential YFV transfusion transmission risk is the use of pathogen inactivation (PI) technology systems, such as THERAFLEX MB-Plasma and THERAFLEX UV-Platelets (Macopharma). We aimed to investigate the efficacy of these PI technology systems to inactivate YFV in plasma or platelet concentrates (PCs). STUDY DESIGN AND METHODS: YFV spiked plasma units were treated using THERAFLEX MB-Plasma system (visible light doses: 20, 40, 60, and 120 [standard] J/cm2 ) in the presence of methylene blue (approx. 0.8 µmol/L) and spiked PCs were treated using THERAFLEX UV-Platelets system (ultraviolet C doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm2 ). Samples were taken before the first and after each illumination dose and tested for residual virus using a modified plaque assay. RESULTS: YFV infectivity was reduced by an average of 4.77 log or greater in plasma treated with the THERAFLEX MB-Plasma system and by 4.8 log or greater in PCs treated with THERAFLEX UV-Platelets system. CONCLUSIONS: Our study suggests the THERAFLEX MB-Plasma and the THERAFLEX UV-Platelets systems can efficiently inactivate YFV in plasma or PCs to a similar degree as that for other arboviruses. Given the reduction levels observed in this study, these PI technology systems could be an effective option for managing YFV transfusion-transmission risk in plasma and PCs.

12.
Antiviral Res ; 168: 121-127, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085206

RESUMO

Dengue virus (DENV) is the most prevalent mosquito-borne flavivirus that infects humans. At present, there are no specific antiviral drugs to treat DENV infection and vaccine development has met with challenges. DENV encodes two glycosaminoglycan (GAG) binding proteins; Envelope (E) and non-structural protein 1 (NS1). While previous work has validated the use of GAG analogues as inhibitors of E mediated virus-cell attachment, their potential for antiviral intervention in NS1 protein toxicity has not yet been explored. Here, we investigate the potential of the heparan sulfate mimetic PG545 as a dual purpose compound to target both DENV virion infectivity and NS1 function. In comparison to a non-sulfated analogue, we show that PG545 potently inhibits DENV infectivity with no cytotoxic effect. Against NS1, PG545 completely blocks the induction of cellular activation and abolishes NS1-mediated disruption of endothelial monolayer integrity. Furthermore, PG545 treatment moderately improves survival from lethal DENV challenge in a murine model. At peak disease, PG545-treated mice have lower viremia, circulating NS1 and serum TNF-α. Consistent with anti-NS1 activity, PG545 treatment also reduces systemic vascular leakage caused by DENV infection in vivo. Taken together, these findings demonstrate that the dual targeting of DENV virions and NS1 using GAG analogues offers a new avenue for DENV drug development.

13.
Chemistry ; 25(22): 5664-5667, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30924209

RESUMO

Stachyonic acid A, arising from the first in-depth phytochemical investigation of the herb Basilicum polystachyon, was found to display potent inhibitory activity against dengue virus, with limited cytotoxicity. Andrographolide, a known dengue virus inhibitor and closely related labdane-type diterpene, is structurally more complex but displayed poor antiviral activity in the PRNT assay, and increased cytotoxicity in comparison. Furthermore, a Diels-Alder reaction with PTAD identified the active pharmacophore of stachyonic acid to be the conjugated diene.


Assuntos
Antivirais/química , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Dengue/tratamento farmacológico , Diterpenos/química , Diterpenos/farmacologia , Descoberta de Drogas , Humanos , Lamiaceae/química , Modelos Moleculares , Replicação Viral/efeitos dos fármacos
14.
Nat Microbiol ; 4(5): 876-887, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30886357

RESUMO

Arboviruses cycle between, and replicate in, both invertebrate and vertebrate hosts, which for Zika virus (ZIKV) involves Aedes mosquitoes and primates1. The viral determinants required for replication in such obligate hosts are under strong purifying selection during natural virus evolution, making it challenging to resolve which determinants are optimal for viral fitness in each host. Herein we describe a deep mutational scanning (DMS) strategy2-5 whereby a viral cDNA library was constructed containing all codon substitutions in the C-terminal 204 amino acids of ZIKV envelope protein (E). The cDNA library was transfected into C6/36 (Aedes) and Vero (primate) cells, with subsequent deep sequencing and computational analyses of recovered viruses showing that substitutions K316Q and S461G, or Q350L and T397S, conferred substantial replicative advantages in mosquito and primate cells, respectively. A 316Q/461G virus was constructed and shown to be replication-defective in mammalian cells due to severely compromised virus particle formation and secretion. The 316Q/461G virus was also highly attenuated in human brain organoids, and illustrated utility as a vaccine in mice. This approach can thus imitate evolutionary selection in a matter of days and identify amino acids key to the regulation of virus replication in specific host environments.


Assuntos
Análise Mutacional de DNA/métodos , Tropismo Viral , Infecção por Zika virus/virologia , Zika virus/fisiologia , Aedes/virologia , Animais , Evolução Biológica , Chlorocebus aethiops , Feminino , Especificidade de Hospedeiro , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Mosquitos Vetores/virologia , Mutação , Seleção Genética , Células Vero , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Replicação Viral , Zika virus/química , Zika virus/genética
15.
Langmuir ; 35(5): 1266-1272, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29801414

RESUMO

Development of antifouling films which selectively capture or target proteins of interest is essential for controlling interactions at the "bio/nano" interface. However, in order to synthesize biofunctional films from synthetic polymers that incorporate chemical "motifs" for surface immobilization, antifouling, and oriented biomolecule attachment, multiple reaction steps need to be carried out at the solid/liquid interface. EKx is a zwitterionic peptide that has previously been shown to have excellent antifouling properties. In this study, we recombinantly expressed EKx peptides and genetically encoded both surface attachment and antibody-binding motifs, before characterizing the resultant biopolymers by traditional methods. These peptides were then immobilized to organosilica nanoparticles for binding IgG, and subsequently capturing dengue NS1 as a model antigen from serum-containing solution. We found that a mixed layer of a short peptide (4.9 kDa) "backfilled" with a longer peptide terminated with an IgG-binding Z-domain (18 kDa) demonstrated selective capture of dengue NS1 protein down to ∼10 ng mL-1 in either PBS or 20% serum.


Assuntos
Incrustação Biológica/prevenção & controle , Imunoglobulina G/metabolismo , Peptídeos/metabolismo , Proteínas Recombinantes/metabolismo , Vírus da Dengue/química , Escherichia coli/genética , Proteínas Imobilizadas/genética , Proteínas Imobilizadas/metabolismo , Imunoglobulina G/química , Nanopartículas/química , Peptídeos/genética , Ligação Proteica , Domínios Proteicos , Engenharia de Proteínas/métodos , Proteínas Recombinantes/genética , Dióxido de Silício/química , Proteínas não Estruturais Virais/metabolismo
16.
Proc Natl Acad Sci U S A ; 115(34): 8609-8614, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30082403

RESUMO

Endogenous retroviruses (ERVs) are proviral sequences that result from colonization of the host germ line by exogenous retroviruses. The majority of ERVs represent defective retroviral copies. However, for most ERVs, endogenization occurred millions of years ago, obscuring the stages by which ERVs become defective and the changes in both virus and host important to the process. The koala retrovirus, KoRV, only recently began invading the germ line of the koala (Phascolarctos cinereus), permitting analysis of retroviral endogenization on a prospective basis. Here, we report that recombination with host genomic elements disrupts retroviruses during the earliest stages of germ-line invasion. One type of recombinant, designated recKoRV1, was formed by recombination of KoRV with an older degraded retroelement. Many genomic copies of recKoRV1 were detected across koalas. The prevalence of recKoRV1 was higher in northern than in southern Australian koalas, as is the case for KoRV, with differences in recKoRV1 prevalence, but not KoRV prevalence, between inland and coastal New South Wales. At least 15 additional different recombination events between KoRV and the older endogenous retroelement generated distinct recKoRVs with different geographic distributions. All of the identified recombinant viruses appear to have arisen independently and have highly disrupted ORFs, which suggests that recombination with existing degraded endogenous retroelements may be a means by which replication-competent ERVs that enter the germ line are degraded.


Assuntos
Retrovirus Endógenos/genética , Phascolarctidae/genética , Recombinação Genética , Animais , Feminino , Masculino , New South Wales
17.
Artigo em Inglês | MEDLINE | ID: mdl-29904520

RESUMO

Science communication is a skill set to be developed through ongoing interactions with different stakeholders across a variety of platforms. Opportunities to engage the general public are typically reserved for senior scientists, but the use of social media in science communication allows all scientists to instantaneously disseminate their findings and interact with online users. The Communication Ambassador program is a social media initiative launched by the Australian Society for Microbiology to expand the online presence and science communication portfolios of early-career scientists. Through their participation in the program, a rotating roster of Australian microbiologists have broadened the online reach of the Society's social media channels as well as their own professional networks by attending and live-tweeting microbiology events throughout the year. We present the Communication Ambassador program as a case study of coordinated social media activity in science communication to the general public, and describe the potential for its applications in science education and training.

18.
J Gen Virol ; 99(6): 832-836, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29741476

RESUMO

A novel negative-sense RNA virus, Aedes aegypti anphevirus, was recently identified in wild Aedes aegypti mosquitoes. We show that this virus is also present in the Aag2 Aedes aegypti cell line and characterize its complete genome and evolutionary history. The Aedes aegypti anphevirus genome is estimated to be 12 916 nucleotides in length, contains four genes and has a genome structure similar to that of other anpheviruses. Phylogenetically, Aedes aegypti anphevirus falls within an unclassified group of insect-specific viruses in the order Mononegavirales that form a sister-group to the chuviruses. Notably, the Aag2 cell line used here was also experimentally infected with dengue virus and naturally contained a Phasi Charoen-like virus and cell-fusing agent virus. All four viruses were at relatively high abundance, with 0.5 % of sequence reads assigned to Aedes aegypti anphevirus. The Aag2 cell line is therefore permissive to efficient co-infection with dengue virus and multiple insect-specific viruses.


Assuntos
Aedes/virologia , Genoma Viral , Vírus de Insetos/genética , Animais , Linhagem Celular , Vírus da Dengue/genética , Insetos Vetores , Vírus de Insetos/fisiologia , Vírus de RNA/genética , Vírus de RNA/fisiologia , Replicação Viral
19.
Adv Exp Med Biol ; 1062: 1-10, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29845521

RESUMO

Arboviruses are a diverse group of vector-borne viruses, many of whose members are the cause of significant human morbidity and mortality. Over the last 30 years, the emergence and/or resurgence of arboviruses have posed a considerable global health threat. The ongoing geographical expansion of the dengue viruses (DENV), along with the explosive outbreaks of West Nile virus (WNV), Chikungunya virus (CHIKV) and more recently, Zika virus (ZIKV) have all served as reminders that new epidemics may emerge at any time from this diversity. A clearer understanding of what mechanisms drive these dramatic changes in vector-host transmission cycles that result in the human population becoming significantly more exposed, will help to prepare us for the next emerging epidemic/pandemic. This Chapter seeks to provide a brief overview of the arboviruses, their mode of transmission and some of the known factors that drive their expansion.


Assuntos
Infecções por Arbovirus/virologia , Arbovirus/fisiologia , Animais , Infecções por Arbovirus/transmissão , Arbovirus/genética , Arbovirus/isolamento & purificação , Saúde Global , Humanos
20.
Adv Exp Med Biol ; 1062: 89-106, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29845527

RESUMO

Recent structural and functional advances provide fresh insight into the biology of the dengue virus non-structural protein, NS1 and suggest new avenues of research. The work of our lab and others have shown that the secreted, hexameric form of NS1 has a systemic toxic effect, inducing inflammatory cytokines and acting directly on endothelial cells to produce the hallmark of dengue disease, vascular leak. We also demonstrated that NS1 exerts its toxic activity through recognition by the innate immune receptor TLR4, mimicking the bacterial endotoxin LPS. This monograph covers the background underpinning these new findings and discusses new avenues for antiviral and vaccine intervention.


Assuntos
Vírus da Dengue/imunologia , Dengue Grave/virologia , Proteínas não Estruturais Virais/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Vírus da Dengue/química , Vírus da Dengue/genética , Células Endoteliais/imunologia , Células Endoteliais/virologia , Humanos , Receptores Virais/genética , Receptores Virais/imunologia , Dengue Grave/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética
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