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Review
. 2006 Jul;3(7):e242.
doi: 10.1371/journal.pmed.0030242. Epub 2006 Jul 25.

Silencing viral infection

Derek M Dykxhoorn  1 , Judy Lieberman
Affiliations
Review

Silencing viral infection

Derek M Dykxhoorn et al. PLoS Med. 2006 Jul.

Abstract

The authors describe recent progress and obstacles to harnessing RNA interference to prevent or treat viral infection.

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Conflict of interest statement

Competing Interests: The National Institutes of Health played no role in the preparation of this essay. JL declares that she has pending patent applications on the use of RNA interference to target HIV infection or fas and other apoptotic or proinflammatory genes activated in response to infection; on the topical application of small interfering RNAs for use as a microbicide or for other antiviral prevention or treatment indications; and on cell-type-specific small interfering RNA delivery using an antibody fragment–protamine fusion protein.

Figures

Figure 1
Figure 1. Possible Targets for Suppressing HIV Replication
siRNAs can be used to silence either viral mRNAs or host genes required for viral entry or replication. This figure shows some possible targets for suppressing HIV replication. Silencing CCR5 can prevent viral entry, while any viral gene can also be silenced to interfere with viral production. siRNAs could also target the viral long term repeat or even the proviral genomic RNA prior to integration, although whether this can be done is controversial. Targeting multiple genes will enhance viral suppression and reduce the chances of viral escape by sequence mutation.
Figure 2
Figure 2. siRNA Antiviral Therapy in Animal Models
(A) Intravaginal application of siRNAs mixed with a transfection lipid inhibits sexual transmission of HSV-2 in mice [ 17]. (B) Intranasal or intratracheal administration of siRNAs, either by themselves or mixed with lipids, protects against respiratory infection in mice [ 12, 13, 15]. (C) Intranasal administration of siRNAs in rhesus macaques protects against SARS coronavirus infection [ 16]. (D) Intravenous injection of siRNAs incorporated into specialized liposomes inhibits a hepatitis B virus replicon [ 19]. (E) Intracerebral injection of siRNAs protects against flavivirus encephalitis [ 10]. HSV-2, herpes simplex virus type 2; HBV, hepatitis B virus; HCV, hepatitis C virus; RSV, respiratory syncytial virus.
See this image and copyright information in PMC

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