Inhibition of alphavirus infection in cell culture and in mice with antisense morpholino oligomers

Autor: Robert E. Blouch, Viktoriya Borisevich, David A. Stein, Yinghong Ma, Slobodan Paessler, Rene Rijnbrand, Natallia Dziuba, Patrick L. Iversen, Alexey Seregin, Haolin Ni, Michele A. Zacks, Nadezhda E. Yun
Rok vydání: 2008
Předmět:
Sindbis virus
Morpholino
Injections
Subcutaneous
Morpholines
government.form_of_government
viruses
Venezuelan equine encephalitis virus
Antisense therapy
Alphavirus
Virus Replication
medicine.disease_cause
Drug Administration Schedule
Article
Virus
Cell Line
Morpholinos
Encephalitis Virus
Venezuelan Equine
Mice
03 medical and health sciences
Cricetinae
Virology
Chlorocebus aethiops
medicine
Animals
Alphavirus infection
Administration
Intranasal
030304 developmental biology
0303 health sciences
Dose-Response Relationship
Drug
biology
Alphavirus Infections
030306 microbiology
Morpholino oligomers
Encephalomyelitis
Venezuelan Equine
Oligonucleotides
Antisense
biology.organism_classification
medicine.disease
3. Good health
Antiviral agents
Viral replication
Drug Design
government
Pathogenic alphaviruses
Zdroj: Virology
ISSN: 0042-6822
DOI: 10.1016/j.virol.2008.03.032
Popis: The genus Alphavirus contains members that threaten human health, both as natural pathogens and as potential biological weapons. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) enter cells readily and can inhibit viral replication through sequence-specific steric blockade of viral RNA. Sindbis virus (SINV) has low pathogenicity in humans and is regularly utilized as a model alphavirus. PPMO targeting the 5′-terminal and AUG translation start site regions of the SINV genome blocked the production of infectious SINV in tissue culture. PPMO designed against corresponding regions in Venezuelan equine encephalitis virus (VEEV) were likewise found to be effective in vitro against several strains of VEEV. Mice treated with PPMO before and after VEEV infection were completely protected from lethal outcome while mice receiving only post-infection PPMO treatment were partially protected. Levels of virus in tissue samples correlated with animal survival. Uninfected mice suffered no apparent ill-effects from PPMO treatment. Thus, PPMO appear promising as candidates for therapeutic development against alphaviruses.
Databáze: OpenAIRE
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