Cellular uptake and biological effects of antisense oligodeoxynucleotide analogs targeted to herpes simplex virus.

Abstract:

:In this study, we synthesized antisense oligodeoxynucleotides (ODNs) with phosphodiester, phosphorothioate (S-ODNs), or methylphosphonate linkages complementary to the splicing acceptor site of immediate-early pre-mRNA 5 of herpes simplex virus type 1 (HSV-1). The antiviral activity of each analog on cytopathic effect in cells infected with HSV-1 or HSV-2 was assessed and compared with the cellular uptake of the analog. We found that antisense S-ODNs showed the most potent antiherpetic activity, with 50% inhibitory concentrations of 5 microM for HSV-1 and 0.25 microM for HSV-2. The antiviral effect of antisense S-ODNs was stronger and longer acting than that of acyclovir. Cell association of S-ODNs was the highest and paralleled antiviral activity. Furthermore, some fluorescein isothiocyanate (FITC)-labeled S-ODNs were recognized in the nuclei in HSV-1 infected cells by confocal laser scanning microscopy. S-ODNs located in the nucleus could access the targeted mRNA, which might be responsible for the antiviral activities. Although our study also showed non-sequence-specific activity, which implies that multiple mechanisms are involved, S-ODNs are a promising novel anti-herpetic agent.

authors

Shoji Y,Shimada J,Mizushima Y,Iwasawa A,Nakamura Y,Inouye K,Azuma T,Sakurai M,Nishimura T

doi

10.1128/AAC.40.7.1670

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

1670-5

issue

7

eissn

0066-4804

issn

1098-6596

journal_volume

40

pub_type

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