Constitutive synthesis of polyoma antisense RNA renders cells immune to virus infection

Ottavio, L.; Sthandier, Olga; Ricci, Laura; Passananti, Claudio; Amati, Paolo

doi:10.1016/0042-6822(92)90613-t

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…Another effective means of reducing gene expression has been the use of antisense technology. Antisense methods have been used effectively to downregulate eukaryotic gene expression in a variety of systems (1,3,6,19). These methods have not been routinely adapted for prokaryotes despite the fact that antisense regulation has been shown to be a natural phenomenon in bacteria (25).…”

mentioning

confidence: 99%

Regulated Antisense RNA Eliminates Alpha-Toxin Virulence in Staphylococcus aureus Infection

Ji¹,

Marra²,

Rosenberg³

et al. 1999

J Bacteriol

127

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The ability to selectively disrupt gene function remains a critical element in elucidating information regarding gene essentiality for bacterial growth and/or pathogenesis. In this study, we adapted atet regulatory expression system for use inStaphylococcus aureus, with the goal of downregulating gene expression via induction of antisense RNA. We demonstrate that this system exhibits a 50- to 100-fold dose-dependent level of induction in bacterial cells grown in culture (i.e., in vitro) and also functions in mice (i.e., in vivo) following oral administration of inducer. To determine whether induced antisense RNA could interfere with chromosomally derived gene expression, we cloned a fragment of theS. aureus alpha-toxin gene (hla) in antisense orientation downstream of the tet promoter system and introduced the construct into S. aureus. Induced antisensehla RNA downregulated chromosomally derived hlagene expression in vitro approximately 14-fold. Similarly, induction ofhla antisense RNA in vivo dramatically reduced alpha-toxin expression in two different murine models of S. aureusinfection. Most importantly, this reduction completely eliminated the lethality of the infection. These results indicate that thetet regulatory system functions efficiently in S. aureus and induced antisense RNA can effectively downregulate chromosomal gene expression both in vitro and in vivo.

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mentioning

confidence: 99%

Regulated Antisense RNA Eliminates Alpha-Toxin Virulence in Staphylococcus aureus Infection

Ji¹,

Marra²,

Rosenberg³

et al. 1999

J Bacteriol

127

View full text Add to dashboard Cite

show abstract

“…This antisense strategy known, there is evidence for several potential mechanisms. It has been proposed that one mechanism of antisense RNAwill allow us to study various MV products with specific molecular probes and to potentially localize the intracellular mechamediated viral resistance is the induction of interferon by double-stranded RNA [3]. This hypothesis is not supported by nism that results in immunosuppression.…”

Section: Resultsmentioning

confidence: 98%

“…It also produces verrucous, longstanding cutaplex virus (HSV), the VZV replicative cycle is supposed to be neous lesions in human immunodeficiency virus (HIV)-inregulated in a cascade of three successive steps involving the fected persons [1][2][3][4][5][6][7][8][9]. Such lesions are frequently associated immediate early, early, and late phases.…”

Section: Varicella-zoster Virus (Vzv) Is Responsible For Chickenpoxmentioning

confidence: 99%

Antisense‐Mediated Resistance to Measles Virus Infection in HeLa Cells

Bell¹,

Whitton²,

Fujinami³

1997

J INFECT DIS

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Endogenous expression of antisense RNA in transfected cells has been explored for use in blocking cellular gene expression and for its antiviral potential. Antisense strategies were used with the goal of blocking measles virus (MV) infection. A recombinant expression plasmid was designed to produce antisense oligonucleotides targeted to the 5' end of the MV nucleocapsid protein mRNA. This construct was transfected into HeLa cells. The transfected cell line and a control cell line expressing a random RNA comprising the same nucleotides were infected with MV and assessed for viral resistance by observation of cytopathic effect (CPE); infectious virus was quantified by viral plaque assay. Both cell lines were also infected with a related paramyxovirus, mumps virus, as a specificity control. Both CPE and infectious virus were reduced by approximately 90% in the antisense-expressing line compared with that in control cells or transfectant cells expressing random RNA. There was no evidence of resistance to infection with mumps virus in any cell line.

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“…The growth rate, location of replication and cytotoxicity of a virus also influence how effective antisense RNA is in inhibiting infection. The antisense RNA approach has been used to inhibit, to various degrees, infection of adenovirus (Miroshnichenko et al, 1989), avian retrovirus , human immunodeficiency virus type 1 (HIV-1 ; Chuah et al, 1994 ;Sczakiel & Pawlita, 1991 ;Sczakiel et al, 1992), human cytomegalovirus (HCMV ; Monte et al, 1996 ;Ripalti et al, 1995), measles virus (Koschel et al, 1995), polyomavirus (Ottavio et al, 1992) and prototype minute virus of mice (Ramirez et al, 1995).…”

Section: Inhibition Of Vesicular Stomatitis Virus In Cells Constitutimentioning

confidence: 99%

Inhibition of vesicular stomatitis virus in cells constitutively expressing an antisense RNA targeted against the virus RNA polymerase gene.

Takacs

Banerjee

1997

Journal of General Virology

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The use of antisense RNA technology to inhibit virus gene expression has the potential to be a safe and effective antiviral therapy. In theory, antisense RNA would bind specifically to its target virus mRNA and block virus infection without interfering with the expression of endogenous genes or the normal functioning of the cell (Baltimore, 1988). The success of the antisense RNA approach depends on factors such as the vector and promoter chosen for stable integration and high level expression of the antisense RNA, the site of integration

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Constitutive synthesis of polyoma antisense RNA renders cells immune to virus infection

Cited by 10 publications

References 17 publications

Regulated Antisense RNA Eliminates Alpha-Toxin Virulence in Staphylococcus aureus Infection

Regulated Antisense RNA Eliminates Alpha-Toxin Virulence in Staphylococcus aureus Infection

Antisense‐Mediated Resistance to Measles Virus Infection in HeLa Cells

Inhibition of vesicular stomatitis virus in cells constitutively expressing an antisense RNA targeted against the virus RNA polymerase gene.

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