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Viruses and RNA interference in mammalian cells

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3. <strong>RNA</strong>i as an antiviral defense <strong>in</strong> plants, <strong>in</strong>sects, <strong>and</strong> <strong>in</strong>tervertebrates<br />

Plants<br />

<strong>RNA</strong> silenc<strong>in</strong>g, as an antiviral response, has been studied widely <strong>in</strong> plants. It provides a<br />

nucleic acid-based defense aga<strong>in</strong>st viruses that can <strong>in</strong>duce systemic immunity:<br />

<strong>RNA</strong> <strong>and</strong> DNA viruses produce virus-derived si<strong>RNA</strong>s, dur<strong>in</strong>g their <strong>in</strong>fection.<br />

(Hamilton <strong>and</strong> Baulcombe, 1999)<br />

Increased viral replication <strong>and</strong> spread was observed, if <strong>RNA</strong>i components <strong>in</strong> plants<br />

are impaired. It was shown that plants, deficient <strong>in</strong> component of <strong>RNA</strong>i, exhibited markedly<br />

enhanced susceptibility to tobacco mosaic virus (TMV) <strong>and</strong> potato virus X (PVX) (Xie et<br />

al., 2001).<br />

A local <strong>and</strong> systemic silenc<strong>in</strong>g signal is <strong>in</strong>itiated upon virus <strong>in</strong>fection. (Baulcombe,<br />

2004)<br />

As a contra-defense aga<strong>in</strong>st <strong>RNA</strong>i pathway, viruses have evolved prote<strong>in</strong>s capable of<br />

suppress<strong>in</strong>g <strong>RNA</strong> silenc<strong>in</strong>g. The first viral suppressors of <strong>RNA</strong> silenc<strong>in</strong>g reported were HC-<br />

Pro <strong>and</strong> the 2b prote<strong>in</strong> encoded by potyviruses <strong>and</strong> cucumoviruses (An<strong>and</strong>alakshmi et al.,<br />

2000; Li et al., 1999). This all is a circumstantial evidence, that <strong>RNA</strong> silenc<strong>in</strong>g serves as an<br />

antiviral defense mechanism <strong>in</strong> plants (D<strong>in</strong>g et al., 2004; van Rij <strong>and</strong> And<strong>in</strong>o, 2006).<br />

Insects<br />

<strong>RNA</strong> silenc<strong>in</strong>g also provides a natural antiviral defense <strong>in</strong> <strong>in</strong>sects. It was demonstrated that:<br />

silenc<strong>in</strong>g <strong>RNA</strong>i components <strong>in</strong> Aedes aegypti result <strong>in</strong> transient <strong>in</strong>crease of S<strong>in</strong>dbis virus<br />

(SINV; family Togaviridae, genus Alphavirus) replication; the production of virus-specific<br />

si<strong>RNA</strong>s <strong>in</strong>dicates that <strong>RNA</strong>i <strong>in</strong> Aedes aegypti is active dur<strong>in</strong>g SINV <strong>in</strong>fection; the <strong>RNA</strong>i<br />

response varies <strong>in</strong> a virus-dependent manner. These data def<strong>in</strong>e important features of <strong>RNA</strong>i<br />

anti-viral defense <strong>in</strong> Aedes aegypti (Campbell et al., 2008).<br />

In addition, it was demonstrated that <strong>RNA</strong>i acts as an antagonist to alphavirus replication <strong>in</strong><br />

mosquitoes (Anopheles gambiae). An <strong>in</strong>crease <strong>in</strong> titer <strong>and</strong> spread of O’nyong–nyong virus<br />

(ONNV) supports an antiviral role of <strong>RNA</strong>i <strong>in</strong> suppression of alphavirus replication <strong>in</strong> its<br />

natural vector, after depletion of RISC components: Argonaute prote<strong>in</strong>s 2 <strong>and</strong> 3. These<br />

observations prove that <strong>RNA</strong>i prohibits ONNV replication <strong>in</strong> Anopheles gambiae, <strong>and</strong> also<br />

suggest that the <strong>in</strong>nate immune response conditions vector competence. The presented data<br />

15

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