Role of simvastatin and methyl-β-cyclodextin on inhibition of poliovirus infection

Liu, Shumei; Rodríguez, Ana V.; Tosteson, Magdalena T.

doi:10.1016/j.bbrc.2006.06.107

Cited by 28 publications

(21 citation statements)

References 36 publications

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“…Data was expressed as mean ± standard deviations from three independent experiments. *p≤0.05, **p≤0.01, and ***p≤0.001 (Liu et al 2006), and cytomegalovirus (Potena et al 2004). Simvastatin has been shown to inhibit the growth of both procyclic and epimastigote forms of trypanosome with an IC 50 value of 25-50 μM (Coppens et al 1995).…”

Section: Discussionmentioning

confidence: 98%

Antileishmanial effect of mevastatin is due to interference with sterol metabolism

2015

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Visceral leishmaniasis (VL) is one of the most severe forms of leishmaniasis which is fatal if left untreated. Sterol biosynthetic pathway in Leishmania is currently being explored for its therapeutic potential. In the present study, we have evaluated the antileishmanial efficacy of mevastatin, a known inhibitor of 3-hydroxy-3-methyl glutaryl-CoA reductase (HMGR) enzyme. Mevastatin inhibited Leishmania donovani promastigotes and intracellular amastigotes with an 50% inhibitory concentration (IC50) value of 23.8 ± 4.2 and 7.5 ± 1.1 μM, respectively, without exhibiting toxicity towards host cell line. Mevastatin also inhibited recombinant L. donovani HMGR (LdHMGR) enzyme activity with an IC50 value of 42.2 ± 3.0 μM. Kinetic analysis revealed that the inhibition of recombinant LdHMGR activity by mevastatin was competitive with HMG-CoA. Mevastatin-treated parasites exhibited 66% reduction in ergosterol levels with respect to untreated parasites. Incubation of mevastatin-treated L. donovani promastigotes with ergosterol resulted in revival of cell growth, whereas cholesterol supplementation failed to cause reversal in cell death. To further prove the specificity of mevastatin for HMGR enzyme, HMGR-overexpressing parasites were used which showed almost threefold resistance to mevastatin. It also induced morphological changes in the parasite accompanied by lipid body accumulation. Hence, antileishmanial effect of mevastatin was due to the inhibition of HMGR, which eventually leads to reduction in ergosterol levels and hence parasite death. The present study may have implications in the treatment of visceral form of leishmaniasis.

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Section: Discussionmentioning

confidence: 98%

Antileishmanial effect of mevastatin is due to interference with sterol metabolism

2015

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“…The assembly of LR depends strictly on cholesterol (34). However, we cannot rule out the possibility that cholesterol may also have a role in later steps of the BDV cell entry process, including fusion between viral and cellular membranes in the late endosome, as occurs with poliovirus (7,30). Nevertheless, our 10 7 ) were incubated with Fc-GP1 (10 g) at 4°C to avoid receptor-mediated internalization of Fc-GP1.…”

Section: Discussionmentioning

confidence: 99%

Borna Disease Virus Requires Cholesterol in both Cellular Membrane and Viral Envelope for Efficient Cell Entry

Clemente

Parseval²,

Perez

et al. 2009

J Virol

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Borna disease virus (BDV), the prototypic member of the family Bornaviridae within the order Mononegavirales, provides an important model for the investigation of viral persistence within the central nervous system (CNS) and of associated brain disorders. BDV is highly neurotropic and enters its target cell via receptor-mediated endocytosis, a process mediated by the virus surface glycoprotein (G), but the cellular factors and pathways determining BDV cell tropism within the CNS remain mostly unknown. Cholesterol has been shown to influence viral infections via its effects on different viral processes, including replication, budding, and cell entry. In this work, we show that cell entry, but not replication and gene expression, of BDV was drastically inhibited by depletion of cellular cholesterol levels. BDV G-mediated attachment to BDV-susceptible cells was cholesterol independent, but G localized to lipid rafts (LR) at the plasma membrane. LR structure and function critically depend on cholesterol, and hence, compromised structural integrity and function of LR caused by cholesterol depletion likely inhibited the initial stages of BDV cell internalization. Furthermore, we also show that viral-envelope cholesterol is required for BDV infectivity.Borna disease virus (BDV) is an enveloped virus with a nonsegmented negative-strand RNA genome whose organization (3Ј-N-p10/P-M-G-L-5Ј) is characteristic of mononegaviruses (6, 28, 46, 48). However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales (8,28,46,49).BDV can infect a variety of cell types in cell culture but in vivo exhibits exquisite neurotropism and causes central nervous system (CNS) disease in different vertebrate species, which is frequently manifested in behavioral abnormalities (19,33,44,53). Both host and viral factors contribute to a variable period of incubation and heterogeneity in the symptoms and pathology associated with BDV infection (14,16,29,42,44). BDV provides an important model for the investigation of both immune-mediated pathological events associated with virus-induced neurological disease and mechanisms whereby noncytolytic viruses induce neurodevelopmental and behavioral disturbances in the absence of inflammation (15,18,41). Moreover, serological data and molecular epidemiological studies suggest that BDV, or a BDV-like virus, can infect humans and that it might be associated with certain neuropsychiatric disorders (17, 24), which further underscores the interest in understanding the mechanisms underlying BDV persistence in the CNS and its effect on brain cell functions. The achievement of these goals will require the elucidation of the determinants of BDV cell tropism within the CNS.

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“…Administration of statins in patients with atherosclerosis is shown to be associated with a decreased risk of subsequent sepsis, and randomized clinical trials of statins for prevention of sepsis are warranted. 17 In addition to the management of sepsis, there are several descriptions concerning the inhibitory effects of reagents on viral replication, including poliovirus, 18 HIV-1, 19 and hepatitis C virus. 20 Furthermore, combined treatment with a statin and caffeine effectively ameliorates lung damage, inhibits viral replication, and is at least as effective as the therapy with oseltamivir and ribavirin in H5N1-, H3N2-, and H1N1-infected mice.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Statins on Cytomegalovirus Production in Human Cells: Comprehensive Analysis of Gene Expression Profiles

Murayama

Liu

et al. 2011

Journal of Experimental & Clinical Medicine

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Background/Purpose: Inhibitory effects of statins on human immunodeficiency virus-1 or poliovirus replication were reported. Our aim was to clarify whether statins could inhibit the replication of cytomegalovirus (CMV) in human cells and to determine the changes in gene expression profiles in host cells treated with statins using a DNA microarray. Methods: Human embryonic lung (HEL) fibroblast cells were infected with CMV (Towne strain) at a multiplicity of infection of 1 and were simultaneously treated with mevastatin, simvastatin, lovastatin, or pravastatin (0.001e10mM). HEL cells were incubated for 6 days, and progeny viral titers were quantified by plaque assay. Time-dependent effects of mevastatin or simvastatin (1mM) on CMV replication were also examined. We determined the effects of mevastatin or simvastatin at concentrations ranging from 0.1mM to 10mM on the expressions of CMV immediate-early-1 (IE-1) and late proteins using Western blotting. Comprehensive analysis of gene expression profiles in HEL cells treated with mevastatin (1mM) was performed with a DNA microarray 1 day after infection. Results: The 50% effective concentration values for the inhibition of CMV titers by mevastatin, simvastatin, lovastatin, and pravastatin were 0.0006mM, 0.0055mM, 0.04mM, and 2.55mM, respectively. Inhibition of viral replication by mevastatin was observed when added 24 hours after infection, whereas that by simvastatin was observed when added 48 hours after infection. Mevastatin decreased the expression of the IE-1 protein, and simvastatin inhibited the expression of the late protein. We observed significant changes of cellular growth/differentiation-associated gene expressions (e.g., downregulated cdk2 mRNA) in HEL cells treated with mevastatin. Conclusion: Our data suggest that treatment with mevastatin could inhibit CMV replication at IE phase through altered expressions of cellular growth/differentiation-associated genes.

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Role of simvastatin and methyl-β-cyclodextin on inhibition of poliovirus infection

Cited by 28 publications

References 36 publications

Antileishmanial effect of mevastatin is due to interference with sterol metabolism

Antileishmanial effect of mevastatin is due to interference with sterol metabolism

Borna Disease Virus Requires Cholesterol in both Cellular Membrane and Viral Envelope for Efficient Cell Entry

Inhibitory Effects of Statins on Cytomegalovirus Production in Human Cells: Comprehensive Analysis of Gene Expression Profiles

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