Fig. 1.

What is the role of mTLR7 in the antiviral response? Many ssRNA viruses (including VSV and influenza viruses) engage host cell receptors that trigger endocytosis. Once within endosomes, these enveloped virions fuse with the membrane to release their capsids into the cytosol. However, maturation and acidification of the endosomal vesicle may damage some viral particles, leading to ssRNA release. Human TLR8 (hTLR8) and mouse TLR7 (mTLR7), which are only expressed within endosomal membranes, recognize ssRNA [especially poly(U) and poly(U/G) motifs in the case of hTLR8], which triggers activation. Their associated signaling pathways involve myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase 4 (IRAK4), and tumor necrosis factor receptor-associated factor 6 (TRAF6), which lead to NF-κB activation and inflammatory cytokine production. mTLR7 and hTLR8 might also activate a MyD88-independent pathway involving IFN regulatory factor 3 (IRF-3), or perhaps another IRF family member. This activation leads to the expression of type I IFNs. mTLR7 may also recognize ssRNA derived from viruses that release directly their capsids into the cytosol through plasma membrane fusion (data not shown). The mechanism by which ssRNA would find its way to the endosome in this case is not clear. TLRs 3 and 9 are also activated by viral nucleic acids: dsRNA- and DNA-bearing unmethylated CpG motifs, respectively.