Post-Exposure Prophylaxis of Murine Rabies with Polyinosinic-Polycytidylic Acid and Chlorite-Oxidized Amylose

Harmon, Maurice W.; Janis, Burton; Levy, Hilton B.

doi:10.1128/aac.6.4.507

Cited by 11 publications

(4 citation statements)

References 13 publications

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“…Similar results with weaker and delayed IFN-a expression compared with other IFN genes were found in other viruses including influenza A virus and Sendai virus (Marié et al, 1998;Osterlund et al, 2005). The importance of IFNs in response to rabies is illustrated by previous studies that found that the administration of IFN-inducing poly(I-C) resulted in various degrees of protection against RV in mice, hamsters, rabbits and monkeys (Harmon et al, 1974;Hilfenhaus et al, 1975). Similarly, it has been noted that IFN-a/b receptor knockout mice had a higher virus titre than immunologically intact mice after infection with RV (Hooper et al, 1998).…”

Section: Discussionsupporting

confidence: 75%

Innate immune responses in raccoons after raccoon rabies virus infection

Srithayakumar

Sribalachandran

Rosatte

et al. 2014

Journal of General Virology

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Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.

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Section: Discussionsupporting

confidence: 75%

Innate immune responses in raccoons after raccoon rabies virus infection

Srithayakumar

Sribalachandran

Rosatte

et al. 2014

Journal of General Virology

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“…This is surprising, as COAM was designed to be biodegradable, is active against many viruses, and has a therapeutic index of 300 -500, i.e., a toxicity profile of an order of magnitude better than that of polyI:C [16]. The suggestion that COAM acts like polyI:C and polyacrylates by induction of endogenous IFN is controversial [17][18][19] and was refuted only recently on the basis of in vitro experiments. In sharp contrast with polyI:C, COAM does not induce IFN and, in vitro, acts as a weak virus entry inhibitor [20].…”

Section: Introductionmentioning

confidence: 99%

Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Starckx

Martens

et al. 2010

Journal of Leukocyte Biology

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Insight into molecular and cellular mechanisms of innate immunity is critical to understand viral pathogenesis and immunopathology and might be exploited for therapy. Whereas the molecular mechanisms of the IFN defense are well established, cellular mechanisms of antiviral immunity are only emerging, and their pharmacological triggering remains unknown. COAM is a polysaccharide derivative with antiviral activity but without comprehension about its mechanism of action. The COAM mixture was fractionated, and prophylactic treatment of mice with COAM polymers of high MW resulted in a conversion from 100% lethal mengovirus infection to an overall survival rate of 93% without obvious clinical sequelae. Differential and quantitative analysis of peritoneal leukocytes demonstrated that COAM induced a profound influx of neutrophils. Selective cell depletion experiments pointed toward neutrophils and macrophages as key effector cells in the rescue of mice from lethal mengovirus. COAM was able to induce mRNA and protein expression of the mouse neutrophil chemokine GCP-2. Binding of GCP-2 to COAM was demonstrated in solution and confirmed by SPR technology. Although COAM was not chemotactic for neutrophils, COAM-anchored muGCP-2 retained chemotactic activity for human and mouse neutrophils. In conclusion, this study established that COAM rescued mice from acute and lethal mengovirus infection by recruiting antiviral leukocytes to the site of infection, as proposed through the induction, binding, and concentration of endogenous chemokines. These findings reinforce the role of neutrophils and macrophages as critical cells that can be manipulated toward antiviral defense.

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“…Treatment with exogenous homologous or heterologous IFN [175,[183][184][185][186] or inducers of IFN, such as polyriboinosinic-polyribocytidylic acid (poly I:C) [187][188][189], its derivatives containing kanamycin and CaCl 2 (PICKCa) [190] or other structural molecules [191] weaker protection, although the incubation period was prolonged in some treated animals [176,183]. Combinations of drugs, including combinations of IFN-inducers, such as poly I:C, and chlorite-oxidized amylose (COAM), a small inducer of interferon [192], or combinations of rabies vaccines and IFN or IFN inducers [193][194][195] were also effective only when administered close to the time of viral challenge, and the protective effects obtained were variable. Finally, neither clinical improvement nor extension of the incubation period was observed when IFN-based therapy was initiated in a primate model at the onset of clinical symptoms [183,196].…”

Section: Interferons and Interferon-inducing Moleculesmentioning

confidence: 99%

Human Rabies Encephalitis Prevention and Treatment: Progress Since Pasteurs Discovery

Dacheux¹,

Delmas²,

Bourhy

2011

IDDT

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Rabies remains one of the most ancient and deadly of human infectious diseases. This viral zoonosis is transmitted principally by the saliva of infected dogs, inducing a form of encephalomyelitis that is almost invariably fatal. Since the first implementation, by Louis Pasteur in 1885, of an efficient preventive post-exposure treatment, more effective protocols and safer products have been developed, providing almost 100% protection if administered early enough. However, this disease still represents a major, but neglected public health problem, with an estimated 55,000 human deaths due to rabies reported each year, mostly in Africa and Asia. Once the first clinical signs appear, there is no effective treatment. A ray of hope emerged in 2004, with the report of a patient recovering from rabies after aggressive, innovative treatment. However, this case was not clearly reproduced and the identification of targets for antiviral treatment in cases of rabies infection remains a major challenge. In this context, this review presents the state-of-the art in the prevention and curative treatment of human rabies. We begin by describing the viral etiological agent and the disease it causes, to provide an essential background to rabies. An overview of the post-exposure prophylaxis of rabies in humans is then given, from its initial implementation to possible future developments. Finally, an analysis of the various antiviral compounds tested in rabies in vitro, in animal models or in humans is presented, focusing in particular on potential new strategies.

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Post-Exposure Prophylaxis of Murine Rabies with Polyinosinic-Polycytidylic Acid and Chlorite-Oxidized Amylose

Cited by 11 publications

References 13 publications

Innate immune responses in raccoons after raccoon rabies virus infection

Innate immune responses in raccoons after raccoon rabies virus infection

Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Human Rabies Encephalitis Prevention and Treatment: Progress Since Pasteurs Discovery

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