3.1 Pathogen-associated molecular patterns (PAMPs)

Cells of the body have internal receptors that allow them to recognise components of viruses. They belong to a family of ten receptors, called Toll-like receptors (TLRs), that recognise components of pathogens. Those most relevant for detection of viral infection are listed in Table 2. They are present in cells of the immune system and epithelial cells in mucous membranes – for example, at sites of potential virus infection.

The importance of the TLRs is demonstrated by the rare individuals who lack them. For example, TLR3 deficiency is associated with susceptibility to herpes simplex infection.

Notice that these receptors face into the endosome. When viruses such as SARS-CoV2 enter a cell they are first taken into an endosome, where the viral capsid is removed, releasing the viral RNA. The released RNA can be immediately recognised by the TLRs facing into the endosome. Recognition of the viral RNA triggers activation of the infected cell via a transcription factor, NFκB, which has been described as a ‘master-switch of inflammation’. One important action of NFκB is to induce the synthesis of Type-1 interferon (IFN), a signalling molecule that helps control viral infection.

NFκB also induces synthesis and secretion of a variety of other signalling molecules, collectively called cytokines which control the development of inflammation; this is normally beneficial for controlling infection. However, excessive cytokines can damage host tissues. You may have heard the term ‘cytokine storm’, which refers to damage produced by excess cytokine production. In some patients, this was a particular problem with COVID-19 infection – where the virus infection was not well-controlled by the immune system, the collateral damage from the cytokines exacerbated the damage caused by the virus.

You will now look at how interferon limits the spread of virus.