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 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An important aspect of the epidemiology of arboviruses is the manner in which the viruses are maintained during winter, dry season, or other adverse environmental periods when their arthropod hosts are inactive. One possibility is that the viruses survive in arthropods. In the case of mosquito-borne viruses, it is probable that such viruses could be maintained in this manner only if they were transmitted from one insect generation to the next by transovarial transmission. Such transmission was reported in 1905 by Marchoux and Simond for yellow fever virus in Aedes aegypti. Other workers were unable to confirm this observation and, until very recently, it was believed to be in error. Interest in transovarial transmission of viruses by mosquitoes was reawakened with the recovery of La Crosse virus from field-collected larvae of Aedes triseriatus in 1972. Among bunyaviruses, transovarial transmission has been observed mainly among the California serogroup viruses in Aedes mosquitoes. Among flaviviruses, transovarial transmission has been demonstrated experimentally for the viruses of principal interest to man, namely, yellow fever, dengue, japanese encephalitis, and St-Louis encephalitis. Thus far, the only field evidence of transovarial transmission of flaviviruses is the isolation of yellow fever virus from Aedes furcifei/taylori males captured in nature in 1977. At present there is not conclusive evidence that transovarial transmission of alphaviruses occurs in mosquitoes. Among rhabdoviruses, transovarial transmission of vesicular stomatitis virus has been demonstrated experimentally at a relatively high rate in phlebotominae flies. Many factors are known to affect the experimental transovarial transmission of viruses. The significance of such transmission in nature can only be assessed by field studies.
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PMID:[Transovarial transmission of arboviruses by mosquitoes (author's transl)]. 611 46

The replication of seven arboviruses in a cell line (TRA-171) derived from a nonhematophagous mosquito was studied. Four serotypes of laboratory adapted and three serotypes of unadapted dengue viruses replicated in the TRA-171 cell line, inducing syncytia. The sensitivity of TRA-171 cells to dengue virus infection was comparable to that of Aedes albopictus or A. pseudoscutellaris cells. Yellow fever, St. Louis encephalitis, and vesicular stomatitis viruses also replicated. All four serotypes of dengue viruses could be plaque assayed with TRA-171 cell cultures.
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PMID:Replication of dengue, yellow fever, St. Louis encephalitis and vesicular stomatitis viruses in a cell line (TRA-171) derived from Toxorhynchites amboinensis. 611 88

The biology, veterinary importance and control of certain Nematocera are described and discussed. Culicoides spp. (family Ceratopogonidae) transmit the arboviruses of bluetongue (BT), African horse sickness (AHS), bovine ephemeral fever (BEF) and Akabane. Some other arboviruses have been isolated from these species, while fowl pox has been transmitted experimentally by Culicoides. These insects are vectors of the parasitic protozoans Leucocytozoon caulleryi and Haemoproteus nettionis, and the parasitic nematodes Onchocerca gutturosa, O. gibsoni and O. cervicalis. They also cause recurrent summer hypersensitivity in horses, ponies, donkeys, cattle and sheep. Farm animals can die as a result of mass attack by Simulium spp., which are also vectors of Leucocytozoon simondi, L. smithi and the filariae O. gutturosa, O. linealis and O. ochengi. Venezuelan equine encephalomyelitis (VEE) and Rift Valley fever (RVF) have been isolated from simuliids, and vesicular stomatitis virus New Jersey strain has been replicated in Simulium vittatum. Simuliids are well known as vectors of O. volvulus, the cause of human onchocercosis (river blindness). The family Psychodidae includes the genera Phlebotomus and Lutzomyia (subfamily Phlebotominae), vectors of Leishmania spp. in humans, dogs and other mammals. Vesicular stomatitis virus Indiana strain has been regularly isolated from phlebotomine sandflies. Mass attack by mosquitoes can also prove fatal to farm animals. Mosquitoes are vectors of the viruses of Akabane, BEF, RVF, Japanese encephalitis, VEE, western equine encephalomyelitis, eastern equine encephalomyelitis and west Nile meningoencephalitis, secondary vectors of AHS and suspected vectors of Israel turkey meningoencephalitis. The viruses of hog cholera, fowl pox and reticuloendotheliosis, the rickettsiae Eperythrozoon ovis and E. suis, and the bacterium Borrelia anserina are mechanically transmitted by mosquitoes. These insects also induce allergic dermatitis in horses. They transmit several filarial worms of both animals and humans, and are of great medical importance as vectors of major human diseases, including malaria, yellow fever, dengue fever and many more diseases caused by arboviruses.
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PMID:Nematocera (Ceratopogonidae, Psychodidae, Simuliidae and Culicidae) and control methods. 771 9

Sf9, the insect cell line commonly used for gene expression by recombinant baculovirus (BV), can be infected by St. Louis encephalitis (SLE) virus, a flavivirus, resulting in a persistent, productive, and cytopathic infection, while retaining the ability to be infected with a recombinant baculovirus (rBV). We now demonstrate using double immunofluorescence that single cells are dually infected with SLE virus and rBV. Fourteen additional viruses including additional flaviviruses, other arbovirus classes, vesicular stomatitis virus (VSV), and herpes simplex virus, type 1 (HSV-1) failed to produce a cytopathic effect (CPE) in Sf9 cells. Plaque assays indicated infectious virus was present for several weeks post-inoculation for Yellow fever (YF), Dengue types 1 and 2 (DEN-1 and DEN-2), Gumbo limbo (GL), Eastern equine encephalomyelitis virus (EEE), Western equine encephalomyelitis virus (WEE), HSV-1, and VSV viruses. For HSV-1, GL, EEE, WEE and VSV, but not for YF, DEN-1 or DEN-2 viruses, this could be attributed solely to survival in the Sf9 cell culture media. Of the 14 viruses tested, only HSV-1 could be detected after 2 weeks in serum-free media. The data indicate that several viruses which are pathogenic for humans are stable for long periods of time at 27 degrees C in the serum-containing media used for cultivation of Sf9 cells. YF, DEN-1 and DEN-2 viruses may replicate in Sf9 cells at extremely low levels. This suggests that adventitious agents which do not produce obvious CPE or interfere with rBV infection or recombinant protein expression could contaminate Sf9 cell cultures or media.
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PMID:Susceptibility of the Sf9 insect cell line to infection with adventitious viruses. 781 53

Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 microM and a compound concentration of >or=300 microM required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection.
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PMID:Triaryl pyrazoline compound inhibits flavivirus RNA replication. 1656 47

Lycorine potently inhibits flaviviruses in cell culture. At 1.2-microM concentration, lycorine reduced viral titers of West Nile (WNV), dengue, and yellow fever viruses by 10(2)- to 10(4)-fold. However, the compound did not inhibit an alphavirus (Western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. The compound exerts its antiviral activity mainly through suppression of viral RNA replication. A Val-->Met substitution at the 9th amino acid position of the viral 2K peptide (spanning the endoplasmic reticulum membrane between NS4A and NS4B proteins) confers WNV resistance to lycorine, through enhancement of viral RNA replication. Initial chemistry synthesis demonstrated that modifications of the two hydroxyl groups of lycorine can increase the compound's potency, while reducing its cytotoxicity. Taken together, the results have established lycorine as a flavivirus inhibitor for antiviral development. The lycorine-resistance results demonstrate a direct role of the 2K peptide in flavivirus RNA synthesis.
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PMID:A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor. 1906 63

A new cell line from the neonate larvae of Aedes aegypti (L) mosquito was established and characterized. The cell line at the 50th passage (P) level consisted of three prominent cell types, i.e., epithelial-like cells (92%), fibroblast-like cells (7%), and giant cells ( approximately 1%). Karyological analysis showed diploid (2n = 6) number of chromosomes in >75% cells at P-50. The growth kinetics studied at 52nd passage level showed approximately tenfold increase in cell number over a 10-d study period. The species specificity studies using DNA amplification fingerprinting profile analysis using RAPD primers demonstrated 100% homology with the host profile showing the integrity of the cell line. Electron microscopy revealed the absence of mycoplasma or other adventitious agents. The cell line supported the multiplication of seven arboviruses, i.e., Chikungunya (CHIK), Japanese encephalitis, West Nile, dengue 2 (DEN-2), Chandipura, vesicular stomatitis, and Chittoor viruses. The cell line did not replicate Ganjam and Kaisodi viruses. CHIK virus yield in the new cell line was approximately 3log and 0.5log 50% tissue culture infective dose (TCID(50))/mL higher than Vero E6 and C6/36 cell lines, respectively. In the case of DEN-2 virus, it yielded 1log TCID(50)/mL higher than Vero E6, but lesser than C6/36 cell line. Due to its high susceptibility to a broad spectrum of viruses, the new cell line may find application in virus isolation during epidemics and in antigen production.
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PMID:Establishment and characterization of a new Aedes aegypti (L.) (Diptera: Culicidae) cell line with special emphasis on virus susceptibility. 1953 52

Dengue virus (DENV), a mosquito-borne flavivirus, is a major public health threat. The virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. Neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of DENV infection. Here, we report a previously undescribed adenosine analog, NITD008, that potently inhibits DENV both in vitro and in vivo. In addition to the 4 serotypes of DENV, NITD008 inhibits other flaviviruses, including West Nile virus, yellow fever virus, and Powassan virus. The compound also suppresses hepatitis C virus, but it does not inhibit nonflaviviruses, such as Western equine encephalitis virus and vesicular stomatitis virus. A triphosphate form of NITD008 directly inhibits the RNA-dependent RNA polymerase activity of DENV, indicating that the compound functions as a chain terminator during viral RNA synthesis. NITD008 has good in vivo pharmacokinetic properties and is biologically available through oral administration. Treatment of DENV-infected mice with NITD008 suppressed peak viremia, reduced cytokine elevation, and completely prevented the infected mice from death. No observed adverse effect level (NOAEL) was achieved when rats were orally dosed with NITD008 at 50 mg/kg daily for 1 week. However, NOAEL could not be accomplished when rats and dogs were dosed daily for 2 weeks. Nevertheless, our results have proved the concept that a nucleoside inhibitor could be developed for potential treatment of flavivirus infections.
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PMID:An adenosine nucleoside inhibitor of dengue virus. 1991 64

Brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. Here we report that brequinar has activity against a broad spectrum of viruses. The compound not only inhibits flaviviruses (dengue virus, West Nile virus, yellow fever virus, and Powassan virus) but also suppresses a plus-strand RNA alphavirus (Western equine encephalitis virus) and a negative-strand RNA rhabdovirus (vesicular stomatitis virus). Using dengue virus serotype 2 (DENV-2) as a model, we found that brequinar suppressed the viral infection cycle mainly at the step of RNA synthesis. Supplementing the culture medium with pyrimidines (cytidine or uridine) but not purines (adenine or guanine) could be used to reverse the inhibitory effect of the compound. Continuous culturing of DENV-2 in the presence of brequinar generated viruses that were partially resistant to the inhibitor. Sequencing of the resistant viruses revealed two amino acid mutations: one mutation (M260V) located at a helix in the domain II of the viral envelope protein and another mutation (E802Q) located at the priming loop of the nonstructural protein 5 (NS5) polymerase domain. Functional analysis of the mutations suggests that the NS5 mutation exerts resistance through enhancement of polymerase activity. The envelope protein mutation reduced the efficiency of virion assembly/release; however, the mutant virus became less sensitive to brequinar inhibition at the step of virion assembly/release. Taken together, the results indicate that (i) brequinar blocks DENV RNA synthesis through depletion of intracellular pyrimidine pools and (ii) the compound may also exert its antiviral activity through inhibition of virion assembly/release.
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PMID:Characterization of dengue virus resistance to brequinar in cell culture. 2060 73

Compound A3 was identified in a high-throughput screen for inhibitors of influenza virus replication. It displays broad-spectrum antiviral activity, and at noncytotoxic concentrations it is shown to inhibit the replication of negative-sense RNA viruses (influenza viruses A and B, Newcastle disease virus, and vesicular stomatitis virus), positive-sense RNA viruses (Sindbis virus, hepatitis C virus, West Nile virus, and dengue virus), DNA viruses (vaccinia virus and human adenovirus), and retroviruses (HIV). In contrast to mammalian cells, inhibition of viral replication by A3 is absent in chicken cells, which suggests species-specific activity of A3. Correspondingly, the antiviral activity of A3 can be linked to a cellular protein, dihydroorotate dehydrogenase (DHODH), which is an enzyme in the de novo pyrimidine biosynthesis pathway. Viral replication of both RNA and DNA viruses can be restored in the presence of excess uracil, which promotes pyrimidine salvage, or excess orotic acid, which is the product of DHODH in the de novo pyrimidine biosynthesis pathway. Based on these findings, it is proposed that A3 acts by depleting pyrimidine pools, which are crucial for efficient virus replication.
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PMID:Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis. 2143 31


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