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Cell stress in infection and inflammation

Viruses overload the host cell's protein synthesis machinery at endoplasmic reticulum (ER) to replicate and cause ER stress. Prolonged ER stress is also implicated in chronic inflammatory diseases such as cystic fibrosis and type II diabetes.
Cell stress in infection and inflammation
The maze of membranes known as the ER acts as quality control for all the proteins coming in and out of a cell. Mutations or various virus infections can cause ER stress and initiate the unfolded protein response (UPR).

The EU-funded ER AND INFECTION (ER function in virus infection) project looked specifically at a number of secretory proteins involved in diseases associated with protein misfolding or viral infection. Following this, the team assessed the role of these ER-targeted proteins in stress and early inflammatory responses such as type-I interferon signalling.

Researchers studied disease-associated proteins and their mutations such as the cystic fibrosis conductance regulator and the low-density lipoprotein receptor linked with familial hypercholesterolaemia. Virus envelope glycoproteins of influenza A virus and human immunodeficiency virus were also on the agenda.

Researchers found that diverse secretory proteins initiated stress and immune signalling profiles from the ER, dependent on the type of protein. Significantly, biochemical analysis revealed a new pathway that uses the UPR to integrate ER stress responses with antiviral immune signalling cascades.

Unlike the typical scenario, the results suggest that type I interferon is not just an antiviral response. ER AND INFECTION concluded that protein-dependent ER stress triggers an interferon response. This in turn could play a significant role in the chronic inflammation often observed in diseases associated with protein misfolding or aggregation.

The ER AND INFECTION discovery that there is a link between ER stress and inflammation pathways indicate that targeting stress could be therapeutically viable. Lowering the economic burden of chronic inflammatory diseases will correspondingly improve the quality of life for ageing populations.

Related information


Virus, ER stress, cystic fibrosis, unfolded protein response, inflammatory responses, chronic inflammatory diseases
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