期刊
VIROLOGY
卷 376, 期 2, 页码 357-370出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2008.03.032
关键词
Venezuelan equine encephalitis virus; sindbis virus; pathogenic alphaviruses; antiviral agents; antisense therapy; morpholino oligomers
类别
资金
- NIAID NIH HHS [UC7 AI070083-029002, UC7 AI070083-019002, K08 AI059491-02, U54 AI057156-01, UC7 AI070083, K08 AI059491-03, K08 AI059491-01, K08 AI059491, U54 AI057156, K08 AI059491-04] Funding Source: Medline
- PHS HHS [A1059491] Funding Source: Medline
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. (C) 2008 Elsevier Inc. All rights reserved.
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