New insights into the antiviral effects of chloroquine

Savarino, Andrea; Trani, Livia Di; Donatelli, Isabella; Cauda, Roberto; Cassone, Antonio

doi:10.1016/s1473-3099(06)70361-9

Cited by 523 publications

(502 citation statements)

References 16 publications

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“…CQ and BAF-A1 were reported to have an inhibitory role in HCV entry (74,75), possibly through their perturbing role in the endocytic pathway. CQ is a drug widely used in the treatment of malaria (76) and a potential anti-HIV agent, as it interferes with the glycosylation of envelope glycoprotein 120 (gp120) in the trans-Golgi apparatus, which requires a low pH (77). Nevertheless, our present results provide a mechanistic basis for the therapeutic application of CQ and BAF-A1 in order to intervene in HCV replication via inhibition of complete autolysosome formation.…”

Section: Activation Of Upr and Complete Autolysosome Fusion Promotesmentioning

confidence: 82%

Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro

Chen²

2011

J. Clin. Invest.

299

420

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Autophagy, a process for catabolizing cytoplasmic components, has been implicated in the modulation of interactions between RNA viruses and their host. However, the mechanism underlying the functional role of autophagy in the viral life cycle still remains unclear. Hepatitis C virus (HCV) is a single-stranded, positivesense, membrane-enveloped RNA virus that can cause chronic liver disease. Here we report that HCV induces the unfolded protein response (UPR), which in turn activates the autophagic pathway to promote HCV RNA replication in human hepatoma cells. Further analysis revealed that the entire autophagic process through to complete autolysosome maturation was required to promote HCV RNA replication and that it did so by suppressing innate antiviral immunity. Gene silencing or activation of the UPR-autophagy pathway activated or repressed, respectively, IFN-β activation mediated by an HCV-derived pathogen-associated molecular pattern (PAMP). Similar results were achieved with a PAMP derived from Dengue virus (DEV), indicating that HCV and DEV may both exploit the UPR-autophagy pathway to escape the innate immune response. Taken together, these results not only define the physiological significance of HCV-induced autophagy, but also shed light on the knowledge of host cellular responses upon HCV infection as well as on exploration of therapeutic targets for controlling HCV infection.

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Section: Activation Of Upr and Complete Autolysosome Fusion Promotesmentioning

confidence: 82%

Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro

Chen²

2011

J. Clin. Invest.

299

420

View full text Add to dashboard Cite

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“…It is possible that differences in CQ dosage and regimen and the limited statistical power of our study account for why we did not observe decreases in viral load as reported in other studies. Since our study, another report showed that a daily dosage of 250 mg CQ, as was given to the majority of the participants in our study, was not sufficient to decrease viral load (20). The effects of CQ in combination therapy studies have been reported to be qualitatively different than the antiretroviral effects and not simply additive (15).…”

Section: Fig 1 Cd8 T-cell Activation Is Decreased In Hiv-infected Imentioning

confidence: 88%

Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection

Murray

Down

Boulware³

et al. 2010

J Virol

122

112

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Increased levels of activated T cells are a hallmark of the chronic stage of human immunodeficiency virus (HIV) infection and are highly correlated with HIV disease progression. We evaluated chloroquine (CQ) as a potential therapy to reduce immune activation during HIV infection. We found that the frequency of CD38+ HLA-DR+ CD8 T cells, as well as Ki-67 expression in CD8 and CD4 T cells, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.

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“…Chloroquine is a lysosomotropic agent that accumulates in the endosomal compartment where it can impair the acidification of the endosome and prevent the conformational changes associated with viral fusion and release into the cytosol. In addition to the effect seen in the endosomal compartment, the drug can also impair viral replication by inhibiting the low–pH‐dependent proteases in the Golgi that would participate in glycosylation of nascent viral proteins 10 . Both of these steps are vital for efficient replication and production of viral products.…”

mentioning

confidence: 99%

Chloroquine is effective against influenza A virus in vitro but not in vivo

Vigerust

McCullers

2007

Influenza Resp Viruses

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Background Chloroquine is an inexpensive and widely available 9‐aminoquinolone used in the management of malaria. Recently, in vitro assays suggest that chloroquine may have utility in the treatment of several viral infections including influenza. Objectives We sought to test whether chloroquine is effective against influenza in vivo in relevant animal models. Methods The effectiveness of chloroquine at preventing or ameliorating influenza following viral challenge was assessed in established mouse and ferret disease models. Results Although active against influenza viruses in vitro, chloroquine did not prevent the weight loss associated with influenza virus infection in mice after challenge with viruses expressing an H1 or H3 hemagglutinin protein. Similarly, clinical signs and viral replication in the nose of ferrets were not altered by treatment. Conclusions Although in vitro results were promising, chloroquine was not effective as preventive therapy in vivo in standard mouse and ferret models of influenza virus infection. This dampens enthusiasm for the potential utility of the drug for humans with influenza.

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New insights into the antiviral effects of chloroquine

Cited by 523 publications

References 16 publications

Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro

Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro

Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection

Chloroquine is effective against influenza A virus in vitro but not in vivo

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