Arsenic Trioxide Inhibits Human T Cell-Lymphotropic Virus-1-Induced Syncytiums by Down-Regulating gp46
Hiromi NabeshiTomoaki YoshikawaHaruhiko KamadaHiroko ShibataToshiki SugitaYasuhiro AbeKazuya NaganoTetsuya NomuraKyoko MinowaTakuya YamashitaNorio ItohYasuo YoshiokaShin‐ichi TsunodaYasuo Tsutsumi
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Abstract:
Adult T-cell leukemia (ATL) is a severe chemotherapy-resistant malignancy associated with prolonged infection by the human T cell-lymphotropic virus 1 (HTLV-1). One approach to prevent the onset of ATL is to inhibit the growth/transmission of HTLV-1 infected cells using arsenic trioxide (As2O3). However, there are no reports on the transmission inhibitory effect of As2O3. In this study, we reveal that As2O3 exerts an inhibitory effect on syncytium formation between HTLV-1 infected MT-2 and HeLa cells. In addition, Western blot analysis revealed that the HTLV-1 derived envelope protein gp46 was down regulated by As2O3 treatment, suggesting that As2O3 may inhibit HTLV-1 virus transmission via down-regulation of gp46. These results suggest that As2O3 may be a promising drug to treat refractory HTLV-1-related diseases.Keywords:
Arsenic Trioxide
Syncytium
HeLa
Cytopathic effect
Endogenous retrovirus
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SUMMARY The cytopathogenicity and production of Newcastle disease virus (NDV) strain Herts cultivated in chick embryo (CE), baby hamster kidney (BHK-21), HEp-2, MDBK and L929 cells was investigated. Infection at high multiplicities (1000 p.f.u./cell) induced cell fusion in cultures of all cell types within 3 h after infection. Infection at low multiplicities (10 to 20 p.f.u./cell) produced extensive cell fusion in CE, BHK-21, HEp-2 and L929 cultures within 24 h, but MDBK cells failed to fuse. The latter cells failed to show high levels of virus haemagglutinin at the cell surface or accumulation of virus products, but infective virus was released to significantly higher titres than from the cell types which fused. However, infected MDBK showed similar levels of virus-induced cell damage to the plasma membrane, as measured by the release of lactate dehydrogenase, to HEp-2 and L929 cells which were susceptible to fusion. The morphology of the c.p.e. produced by strain Herts in the different cell types is described. The relationship of virus accumulation and virus release to the process of cell fusion is discussed.
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Cytopathic effect
Cell fusion
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SUMMARY A new virus has been isolated by inoculation of lung tissues of diseased snakes into snake embryos. Homogenates of infected embryo tissues caused c.p.e. in cell cultures incubated at 30 °C. The virus replicates in a wide variety of reptilian or mammalian cell types incubated at 30 °C, inducing either syncytium formation or minimal or no cytopathic changes. Efficient replication occurs in embryonated hens′ eggs at 27 to 30 °C. The virus haemagglutinates guinea pig and chick erythrocytes; it possesses a neuraminidase similar to the receptor-destroying enzyme of Vibrio cholera. Electron microscopic observations of infected cells examined in thin section revealed pleomorphic viruses 146 to 321 nm in diam. resembling known myxoviruses. Internal nucleocapsid strands are 15 to 16 nm in diam.; nucleocapsid observed in negatively stained preparations measures 14 nm in diam. The virus was determined to possess a nucleoprotein core containing a 50S single-stranded unsegmented RNA genome. All characters of the virus are similar to those of the paramyxovirus group except that the nucleocapsid diam. is intermediate between that of paramyxoviruses and pneumoviruses. The virus is antigenically distinct from known myxoviruses and is unique among myxoviruses in its restriction to growth at temperature below 37 °C.
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Growth and cytopathogenicity of pigeon herpes encephalomyelitis virus (PHEV) in avian and mammalian cell cultures were investigated. The virus was cytopathogenic to all avian primary cell cultures tested and produced large syncytia with intranuclear inclusions. Viral antigen was detected in the nuclei of infected cells 6 hr postinoculation. Infective virus, however, was obtained 8 hr post-inoculation. Maximum virus yields in avian cell cultures were reached 72 hr postinoculation. In mammalian cell lines tested, the virus proved to be cytopathogenic except in swine embryo kidney cell lines. The cytopathic effect in mammalian cell lines was characterized by the rounding and clumping of cells., Moderate virus yields were obtained with lamb kidney and bovine embryo thymus cell lines, but not with other cell lines tested. Growth behavior of the virus in cell cultures in comparison with other human and avian herpesviruses is discussed.
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ABSTRACT Despite all the advantages that cell‐cultured influenza vaccines have over egg‐based influenza vaccines, the inferior productivity of cell‐culture systems is a major drawback that must be addressed. BST‐2 (tetherin) is a host restriction factor which inhibits budding‐out of various enveloped viruses from infected host cells. We developed BST‐2‐deficient MDCK and Vero cell lines to increase influenza virus release in cell culture. BST‐2 gene knock‐out resulted in increased release of viral particles into the culture medium, by at least 2‐fold and up to 50‐fold compared to release from wild‐type counterpart cells depending on cell line and virus type. The effect was not influenza virus/MDCK/Vero‐specific, but was also present in a broad range of host cells and virus families; we observed similar results in murine, human, canine, and monkey cell lines with viruses including MHV‐68 (Herpesviridae), influenza A virus (Orthomyxoviridae), porcine epidemic diarrhea virus (Coronaviridae), and vaccinia virus (Poxviridae). Our results suggest that the elimination of BST‐2 expression in virus‐producing cell lines can enhance the production of viral vaccines. Biotechnol. Bioeng.2017;114: 2289–2297. © 2017 Wiley Periodicals, Inc.
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The interaction between 2 strains of group A streptococci in L-forms and the cells of the continuous cell lines HEp, HeLa, L, GPK and PEK, as well as the cells of primary human and chick embryo cell cultures was studied under conditions of infection with different doses. In most of the cell cultures used in this study L-form of streptococci showed no pronounced cytopathic effect. They could be isolated, when using cell cultures as inoculum, from the cultivated cells of continuous cell lines during the whole period of the cultivation of the infected monolayer (6--7 days), primary human embryo cell culture up to days 8--11 and from chick embryo cell culture up to days 1--3. In the cells of the continuous cell lines the maximum amount of L-forms was revealed on days 2--3 by the immunofluorescent technique. The ultrathin sections of HEp and HeLa cells infected with L-forms of streptococci were found to contain small elements similar to L-forms inside the cells and on their surface, which was not detected in the infected primary cell cultures.
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The mechanism of human immunodeficiency virus type 1 (HIV-1) cytopathicity is poorly understood and might involve formation of multinucleated giant cells (syncytia), single-cell lysis, or both. In order to determine the contributions of the fusion domain to syncytium formation, single-cell lysis, and viral infectivity and to clarify the molecular details of these events, insertion mutations were made in the portion of env encoding this sequence in the functional HIV-1 proviral clone HXB2. Viruses produced from these mutant clones were found to have a partial (F3) or complete (F6) loss of syncytium-forming ability in acutely infected CEM, Sup T1, and MT4 T-cell lines. During the early stage of acute infection by F6 virus, there was a loss of the syncytial cytopathic effect, which resulted in increased cell viability, and a 1.9- to 2.6-fold increase in virus yield in the cell lines tested. In the late stage of acute infection, the single-cell cytopathic effect of F6 virus was similar to that of the parental HXB2 virus. The F3 and F6 viruses were also found to have a 1.7- to 43-fold reduction in infectivity compared with the HXB2 virus. The mutant F3 and F6 and parental HXB2 envelope proteins were expressed in vaccinia virus, and the mutant envelope proteins were observed to be defective in their ability to form syncytia. BSC-40 cells infected with vaccinia virus recombinants revealed no differences in kinetics of cleavage, cell surface expression, or CD4 binding capacity of the mutant and parental envelope proteins. These results demonstrate that a loss of syncytium formation results in an attenuation of infectivity and a loss of the syncytial cytopathic effect without a loss of single-cell lysis. These mutants may reflect in tissue culture the changes observed in the HIV isolates in vivo during disease progression, which exhibit marked differences in syncytium production.
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