Effect of interferon-α and cell differentiation on Puumala virus infection in human monocyte/macrophages

Temonen, Mari; Lankinen, Hilkka; Vapalahti, Olli; Ronni, Tapani; Julkunen, Ilkka; Vaheri, Antti

doi:10.1016/s0042-6822(95)80014-x

Cited by 46 publications

(35 citation statements)

References 31 publications

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“…Serum levels of TNF-α showed a decrease at days 8, 12, and 16 pi, which may be due to secreted TNF-α binding to TNF-α receptors (TNFR) expressed in the cell membrane or secreted in serum [30][31][32] ; thus, resulting in less detection of secreted TNF-α. Higher levels of TNF-α were detected in arbidoltreated animals than placebo controls, suggesting that the mechanism of action of arbidol may not only involve modu-1023 www.chinaphar.com Deng HY et al Acta Pharmacologica Sinica npg lating serum TNF-α levels but also expression of TNFR in the tissues [32][33][34] . Therefore, it is possible that apart from exhibiting anti-HTNV activity, arbidol could have also modulated the TNF responses and protected mice against the lethal challenge.…”

Section: Arbidol Is Effective Against Htnv In Vivomentioning

confidence: 99%

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

et al. 2009

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Aim: Arbidol is an immunomodulator that was first developed in Russia. In this study, we report the antiviral activity of arbidol against Hantaan virus (HTNV) in vitro and in vivo. Methods: The antiviral activity of arbidol in vitro was determined by plaque-forming assay, ranging from 0.5 to 8 μg/mL. To investigate whether arbidol has an antiviral effect in vivo, suckling BALB/c mice infected with HTNV were treated with arbidol at 24 h before infection with a 5, 10 or 20 mg·kg -1 ·d -1 , once per day, for 10 days. On day 12 and 28 post infection (pi), histopathological changes and viral antigen were detected. On days 4, 8, 12, and 16 pi, the viral load of target organs and serum TNF-α levels of arbidol-treated animals were determined. Results: Arbidol was found to have potent inhibitory activity against HTNV when added in vitro before or after viral infection, with a 50% inhibitory concentration (IC 50 ) of 0.9 and 1.2 μg/mL, respectively. The 50% lethal dose (LD 50 ) of arbidol for suckling mice was 78.42 mg·kg -1 ·d -1 . Oral administration of arbidol increased both survival rate and mean time to death (MTD). Treatment with arbidol reduced histopathological changes, decreased viral load and viral antigen levels, and modulated the level of serum TNF-α. Conclusion: Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.

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Section: Arbidol Is Effective Against Htnv In Vivomentioning

confidence: 99%

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

et al. 2009

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“…Several bunyaviruses are known to be sensitive to the effects of IFN (16,31,39). It was therefore possible that because of the high levels of IFN induced by BUNdelNSs, the mutant virus has a reduced growth rate in IFN-competent cells.…”

Section: Expression Of Nss Blocks Activation Of the Ifn-␤ Promotermentioning

confidence: 99%

Bunyamwera Bunyavirus Nonstructural Protein NSs Counteracts the Induction of Alpha/Beta Interferon

Weber

Bridgen

Fazakerley

et al. 2002

J Virol

195

185

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Production of alpha/beta interferons (IFN-␣/␤) in response to viral infection is one of the main defense mechanisms of the innate immune system. Many viruses therefore encode factors that subvert the IFN system to enhance their virulence. Bunyamwera virus (BUN) is the prototype of the Bunyaviridae family. By using reverse genetics, we previously produced a recombinant virus lacking the nonstructural protein NSs (BUNdelNSs) and showed that NSs is a nonessential gene product that contributes to viral pathogenesis. Here we demonstrate that BUNdelNSs is a strong inducer of IFN-␣/␤, whereas in cells infected with the wild-type counterpart expressing NSs (wild-type BUN), neither IFN nor IFN mRNA could be detected. IFN induction by BUNdelNSs correlated with activation of NF-B and was dependent on virally produced double-stranded RNA and on the IFN transcription factor IRF-3. Furthermore, both in cultured cells and in mice lacking a functional IFN-␣/␤ system, BUNdelNSs replicated to wild-type BUN levels, whereas in IFN-competent systems, wild-type BUN grew more efficiently. These results suggest that BUN NSs is an IFN induction antagonist that blocks the transcriptional activation of IFN-␣/␤ in order to increase the virulence of Bunyamwera virus.

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“…Mx proteins are induced by type I IFNs and possess important antiviral properties. Human MxA and rodent Mx2, in particular, confer resistance against hantaviruses, including Seoul virus, Puumala virus, Hantaan virus, and Andes virus, in vitro (Jin et al, 2001;Khaiboullina et al, 2005;Temonen et al, 1995). The expression of Mx2 is suppressed in male rats during Seoul virus infection and may contribute to increased virus shedding and viral RNA levels in lung tissue (Klein et al, 2004a).…”

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Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats

Hannah

Bajic

Klein

2008

Brain, Behavior, and Immunity

139

142

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Among rodents that carry hantaviruses, more males are infected than females. Male rats also have elevated copies of Seoul virus RNA and reduced transcription of immune-related genes in the lungs than females. To further characterize sex differences in antiviral defenses and whether these differences are mediated by gonadal hormones, we examined viral RNA in the lungs, virus shedding in saliva, and antiviral defenses among male and female rats that were intact, gonadectomized neonatally, or gonadectomized in adulthood. Following inoculation with Seoul virus, high amounts viral RNA persisted longer in lungs from intact males than intact females. Removal of the gonads in males reduced the amount of viral RNA to levels comparable with intact females at 40 days postinoculation (p.i.). Intact males shed more virus in saliva than intact females 15 days p.i.; removal of the gonads during either the neonatal period or in adulthood increased virus shedding in females and decreased virus shedding in males. Induction of pattern recognition receptors (PRRs; TLR7 and RIG-I), expression of antiviral genes (Myd88, VISA, Jun, IRF7, IFNβ, IFNAR1, JAK2, STAT3, and Mx2), and production of Mx protein was elevated in the lungs of intact females compared with intact males. Gonadectomy had more robust effects on the induction of PRRs than on downstream IFNβ or Mx2 expression. Putative androgen and estrogen response elements are present in the promoters of several of these antiviral genes, suggesting the propensity for sex steroids to directly affect dimorphic antiviral responses against Seoul virus infection.

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Effect of interferon-α and cell differentiation on Puumala virus infection in human monocyte/macrophages

Cited by 46 publications

References 31 publications

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

Bunyamwera Bunyavirus Nonstructural Protein NSs Counteracts the Induction of Alpha/Beta Interferon

Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats

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