Less is more: Biased loss of CpG dinucleotides strengthens antiviral immunity

Abstract

Viruses may not only affect our daily lives but also shape our genome evolution. A recent study shows that the zinc-finger antiviral protein (ZAP) drives CpG suppression in a biased manner. Genes involved in the defense against viral invaders are particularly CpG suppressed to avoid self-targeting and to promote an effective immune response.

Fig 1. Biased CpG suppression in cellular genes to maintain efficient innate antiviral immune responses in the presence of the antiviral factor ZAP.

Uninfected cells (left) express a large variety of mRNAs showing significant but varying magnitudes of CpG suppression. Virus infection (middle) triggers the IFN response associated with strong induction of IFNs and numerous ISGs, expressing a large array of structurally and functionally diverse antiviral factors. One of them is ZAP, which mediates degradation of CpG-rich viral as well as cellular mRNAs. Particularly strong CpG suppression allows mRNAs encoding IFNs and antiviral factors to evade degradation by ZAP and, thus, to maintain an effective antiviral state (right). Some cellular genes are suppressed by the IFN response, and this effect is partly dependent on ZAP expression. Whether IRGs might otherwise promote viral replication directly or by attenuating the antiviral immune response remains to be determined. Color coding of viral and cellular RNA species and symbols is explained on the left. IFN, interferon; IRG, interferon-repressed gene; ISG, interferon-stimulated gene; ZAP, zinc-finger antiviral protein.