Short-interfering RNAs as antivirals against rabies

Brandão, Paulo Eduardo; Castilho, Juliana Galera; Fahl, W. O.; Carnieli, Pedro; Oliveira, Rafael de Novaes; Macedo, Carla Isabel; Carrieri, Maria Luíza; Kotait, Ivanete

doi:10.1590/s1413-86702007000200011

Cited by 32 publications

(28 citation statements)

References 11 publications

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“…These results demonstrate that all three siRNAs used in this study are similarly efficient when used in separate or as pools, as described by Brandão et al (2007).…”

Section: Discussionsupporting

confidence: 78%

“…The siRNAs described by Brandão et al (2007) (Table 1), complementary to different regions of RABV N protein mRNA, were synthesized in a duplex format with two deo-xi-timidines at the 3′ end of each sense and anti-sense strands and resuspended as instructed by the manufacturers (Invitrogen, Carlsbad, CA, USA) and used for cell and mice trials.…”

Section: Methodsmentioning

confidence: 99%

“…The search for antivirals against rabies is one of the frontiers in the field but, despite a protocol (the Milwaukee Protocol) based on ketamin, ribavirin, midazolam and amantadin was successful after the treatment of a human patient (Willoughby et al , 2005), it was shown as not reproducible. RNA interference is an alternative as antiviral technology against RABV already shown as effective in vitro in cell cultures (Brandão et al , 2007; Israsena et al , 2009), but no reports on its in vivo use exist hitherto.…”

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo inhibition of rabies virus replication by RNA interference

Ono

Iamamoto

Castilho³

et al. 2013

Braz. J. Microbiol.

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Rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (RABV) (Mononegavirales: Rhabdoviridae: Lyssavirus). Currently, human rabies treatment is based on the Milwaukee Protocol which consists on the induction of coma and massive antiviral therapy. The aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering RNAs. To this end, three siRNAs were used with antisense strands complementary to rabies virus nucleoprotein (N) mRNA. BHK-21 cells monolayers were infected with 1000 to 0.1 TCID50 of PV and after 2 hours the cells were transfected with each of tree RNAs in separate using Lipofectamine-2000. All three siRNAs reduced the titer of PV strain in a least 0.72 logTCID50/mL and no cytotoxic effect was observed in the monolayers treated with Lipofectamine-2000. Swiss albino mice infected with 10.000 to 1 LD of PV strain by the intracerebral route were also transfected after two hours of infection with a pool 3 siRNAs with Lipofectamine-2000 by the intracerebral route, resulting in a survival rate of 30% in mice inoculated with 100 LD50, while the same dose led to 100% mortality in untreated animals. Lipofectamine-2000 showed no toxic effect in control mice. These results suggest that intracerebral administration of siRNAs might be an effective antiviral strategy for rabies.

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“…These results demonstrate that all three siRNAs used in this study are similarly efficient when used in separate or as pools, as described by Brandão et al (2007).…”

Section: Discussionsupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro and in vivo inhibition of rabies virus replication by RNA interference

Ono

Iamamoto

Castilho³

et al. 2013

Braz. J. Microbiol.

Self Cite

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show abstract

“…There has been a dramatic increase in the number of new and developing viral therapeutic options including RNA-based therapies such as RNA interference (RNAi), aptamers and microRNA (miRNA)-based therapies. RNAi has thus far only been applied in a limited number of studies with regards to rabies [174,175,176,177,178,179,180], but has shown great potential, both within rabies, as well as in other viral diseases where research is at a more advanced stage [181]. However, several challenges still remain, including that of identifying the ideal targets for knockdown and the means of targeted delivery.…”

Section: Discussionmentioning

confidence: 99%

Subversion of the Immune Response by Rabies Virus

Scott

Nel

2016

Viruses

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Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses—including age, sex, cerebral lateralization and temperature—are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host’s response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment.

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“…Initially, plasmids encoding siRNA, or another form of RNAi that target specific RABV genes, were constructed and tested for anti-rabies efficacy [124,125,126]. Although the plasmid-based approaches achieved some degree of anti-rabies effect, the low efficiency of siRNA delivery hindered the substantial protection against RV through anti-rabies RNAi approach.…”

Section: Other Novel Modalities For Rabies Control and Preventionmentioning

confidence: 99%

Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

Zhu

Guo

2016

Viruses

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Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.

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Short-interfering RNAs as antivirals against rabies

Cited by 32 publications

References 11 publications

In vitro and in vivo inhibition of rabies virus replication by RNA interference

In vitro and in vivo inhibition of rabies virus replication by RNA interference

Subversion of the Immune Response by Rabies Virus

Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

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