Inhibition of norovirus replication by morpholino oligomers targeting the 5′-end of the genome

被引：13

作者：

Bok, Karin ^{[1
]}

Cavanaugh, Victoria J. ^{[2
]}

Matson, David O. ^{[2
,3
,4
]}

Gonzalez-Molleda, Lorenzo ^{[5
]}

Chang, Yeong-Ok ^{[6
]}

Zintz, Carmelann ^{[2
,3
,4
]}

Smith, Alvin W. ^{[7
]}

Iversen, Patrick ^{[8
]}

Green, Kim Y. ^{[1
]}

Campbell, Ann E. ^{[2
]}

机构：

[1] NIAID, Infect Dis Lab, NIH, DHHS, Bethesda, MD 20892 USA

[2] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23507 USA

[3] Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA 23507 USA

[4] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA

[5] Univ Oviedo, Asturias Inst Biotechnol, Dept Biochem & Mol Biol, Oviedo, Spain

[6] Kansas State Univ, Manhattan, KS 66506 USA

[7] Oregon State Univ, Lab Calicivirus Studies, Corvallis, OR USA

[8] AVI BioPharma Inc, Corvallis, OR 97333 USA

来源：

VIROLOGY | 2008年 / 380卷 / 02期

关键词：

Norovirus; Antisense; PMO; Antiviral;

D O I：

10.1016/j.virol.2008.08.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Noroviruses are an important cause of non-bacterial epidemic gastroenteritis, but no specific antiviral therapies are available. We investigated the inhibitory effect of phosphorodiamidiate morpholino oligomers (PMOs) targeted against norovirus sequences. A panel of peptide-conjugated PMOs (PPMOs) specific for the murine norovirus (MNV) genome was developed, and two PPMO compounds directed against the first AUG of the ORF1 coding sequence near the 5'-end of the genome proved effective in inhibiting MNV replication in cells. A consensus PPMO (designated Noro 1.1), designed to target the corresponding region of several diverse human norovirus genotypes, decreased the efficiency of protein translation in a cell-free luciferase reporter assay and inhibited Norwalk virus protein expression in replicon-bearing cells. Our data suggest that PPMOs directed against the relatively conserved 5'-end of the norovirus genome may show broad antiviral activity against this genetically diverse group of viruses. Published by Elsevier Inc.

引用

页码：328 / 337

页数：10

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