Antiviral Efficacy and Toxicity of Ribavirin and Foscarnet Each Given Alone or in Combination in the Murine AIDS Model

Omar, Rabeea F.; Harvie, Pierrot; Gourde, Pierrette; Désormeaux, André; Tremblay, Michel J.; Beauchamp, Denis; Bergeron, Michel G.

doi:10.1006/taap.1996.8080

Cited by 5 publications

(3 citation statements)

References 50 publications

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“…Although data from animal models suggest mitochondrial damage, 41 the potential for mitochondrial toxicity seems to be relatively low in uninfected cells. 42 Most patients received this prophylaxis or treatment without detectable clinical deterioration.…”

Section: Consensus Proposalmentioning

confidence: 98%

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach

Halter

Schüpbach

Casali

et al. 2010

Bone Marrow Transplant

106

139

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Allogeneic hematopoietic SCT (HSCT) has been proposed as a treatment for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). HSCT has been performed in nine patients using different protocols with varying success. Based on this preliminary experience, participants of the first consensus conference propose a common approach to allogeneic HSCT in MNGIE. Standardization of the transplant protocol and the clinical and biochemical assessments will allow evaluation of the safety and efficacy of HSCT as well as optimization of therapy for patients with MNGIE.

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Section: Consensus Proposalmentioning

confidence: 98%

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach

Halter

Schüpbach

Casali

et al. 2010

Bone Marrow Transplant

106

139

View full text Add to dashboard Cite

show abstract

“…OW arenaviruses LASV and LUJV and NW arenavirus JUNV, MACV, GTOV and CHPV have features that make them credible biodefense threats and have been included by the National Institute of Allergy and Infectious Diseases (NIAID) as Category A biological agents that pose a significant biodefense concern [ 35 ]. Concerns about human pathogenic arenavirus infections are aggravated by the lack of Food and Drug Administration (FDA)-licensed vaccines and antiviral drug treatment being limited to the use of ribavirin [ 36 ] that is only partially effective, associated with significant side effects and must be administrated early, and intravenously, during viral infection for optimal efficacy [ 37 , 38 , 39 ]. Evidence indicates that with morbidity and mortality of LASV, and other HF arenaviruses, infections are associated with the failure of the host’s innate immune response to restrict virus replication and to facilitate the initiation of an effective adaptive immune response [ 9 ].…”

Section: Arenaviruses and Their Impact On Human Healthmentioning

confidence: 99%

“…Anemia and congenital disorders are two significant side effects associated with the use of ribavirin. In addition, oral administration is significantly less effective than intravenous administration, which poses logistic complications in regions with limited clinical infrastructure [ 37 , 38 , 39 ].…”

Section: Current Strategies To Combat Human Arenavirus Infectionsmentioning

confidence: 99%

Reporter-Expressing, Replicating-Competent Recombinant Arenaviruses

Martínez-Sobrido

Torre

2016

Viruses

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Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug Administration (FDA)-licensed vaccines are available to combat human arenavirus infections, and current anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetic approaches has provided investigators with a novel and powerful approach for the study of arenavirus biology including virus–host interactions underlying arenavirus induced disease. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription, as well as particle assembly and budding. Likewise, it is now feasible to rescue infectious arenaviruses containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis. The use of reverse genetics approaches has also allowed the generation of recombinant arenaviruses expressing additional genes of interest. These advances in arenavirus molecular genetics have also facilitated the implementation of novel screens to identify anti-arenaviral drugs, and the development of novel strategies for the generation of arenavirus live-attenuated vaccines. In this review, we will summarize the current knowledge on reporter-expressing, replicating-competent arenaviruses harboring reporter genes in different locations of the viral genome and their use for studying and understanding arenavirus biology and the identification of anti-arenaviral drugs to combat these important human pathogens.

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Reverse Genetics Approaches to Control Arenavirus

Martínez-Sobrido¹,

Cheng²,

Torre³

2016

Vaccine Design

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Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors.

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Antiviral Efficacy and Toxicity of Ribavirin and Foscarnet Each Given Alone or in Combination in the Murine AIDS Model

Cited by 5 publications

References 50 publications

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach

Reporter-Expressing, Replicating-Competent Recombinant Arenaviruses

Reverse Genetics Approaches to Control Arenavirus

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