INHIBITION OF INFLUENZA-VIRUS REPLICATION BY PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES

被引:85
作者
LEITER, JME [1 ]
AGRAWAL, S [1 ]
PALESE, P [1 ]
ZAMECNIK, PC [1 ]
机构
[1] WORCESTER FDN EXPTL BIOL INC,CELL BIOL GRP,SHREWSBURY,MA 01545
关键词
antisense DNA; antiviral; RNa virus;
D O I
10.1073/pnas.87.9.3430
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Oligodeoxynucleotides (ODNs) were synthesized and tested for their antiviral activity against influenza viruses. ODNs corresponded to the polymerase PB1 gene of either influenza A/WSN/33 virus or influenza C/JJ/50 virus. All compounds were 20 nucleotides long, including control ODNs containing mismatches. The phosphodiester ODNs (O-ODNs) failed to inhibit replication of influenza A and influenza C viruses at concentrations up to 80 μM, possibly due to intracellular nuclease digestion of the unmodified oligomers. By contrast, the phosphorothioate derivatives (S-ODNs) were found to inhibit replication of both influenza A and influenza C virus. The antiviral effect of S-ODNs against influenza A virus was found at concentrations as low as 1.25 μM and was present with mismatched oligomers. In the case of influenza C virus, the S-ODN complementary to the 3' end of the viral RNA of the PB1 gene revealed a sequence-specific antiviral activity at a concentration of 20 μM. (At the same concentration, S-ODNs with one or three mismatches showed little or no antiviral activity.) Reduction in plaque number reached six logarithms when this sequence-specific S-ODN was used at a concentration of 80 μM.
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页码:3430 / 3434
页数:5
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