1. Viruses and other informational parasites are a ‘fact of life’ 304

2. Evolution drives diversity in viral strategies and host interactions 304

3. Cellular defense often involves recognizing nucleic acid structures that are indicative of unwanted information duplication 305

3.1 Double-stranded RNA (dsRNA) 305

3.2 Single-stranded DNA (ssDNA) 305

3.3 Unspliced mRNAs 306

3.4 Polycistronic mRNAs 306

3.5 Multi-copy DNAs 306

3.6 Other structures 306

4. dsRNA as a case study: building a multilevel response to foreign structure 306

5. Getting there is half the fun: disseminated immunity in RNAi 308

6. Viruses strike back … so why do we still get sick? 308

Cells face a constant struggle against unwanted instructions that arrive in the form of viruses and transposons. At the core of this battle are two issues: how can cellular machinery recognize certain informational molecules as ‘unwanted’ and how can the cell use this recognition to effectively silence malicious genetic activity. While defenses against some specific parasites may be triggered by individual nucleic acid or protein sequences, such sequence-specific mechanisms have the limitation of allowing the parasite to evade following relatively minor evolutionary change. A more general set of defense mechanisms is based on recognition of structural features that are intrinsic aspects of one or more parasitic lifestyle. Recognition of extended regions of double-stranded RNA (dsRNA) provides cells with one such defensive modality. Essentially absent during ‘normal’ gene expression, long stretches of dsRNA within a cell serve as a dramatic warning that a segment of information may be replicating as RNA. In addition to exemplifying many of the mechanistic issues in genome defense, the cellular response to dsRNA provides several examples of the logic by which organisms attempt to focus their limited immunity resources on the most immediate and dangerous targets.