Preventing G protein cleavage increases respiratory syncytial virus titers

What is it about?

Candidate live, attenuated respiratory syncytial virus (RSV) vaccines are propagated in Vero cells, where most of the virion attachment (G) glycoprotein is cleaved. As a result, Vero cell-propagated RSV is 5-fold less infectious for primary human airway epithelial (HAE) cells, the natural RSV target. We demonstrate that the G protein is cleaved by cathepsin L, likely during endocytic recycling, and identified a 7-residue cluster that regulates G protein cleavage. Infection of Vero cells with RSV containing a mutation in this cluster yields progeny with 5-fold enhanced infectivity for HAE cultures. Such mutations should reduce RSV vaccine production costs.

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Why is it important?

Modifying the G protein so that the protein cannot be cleaved should increase entry of candidate vaccine viruses so that less total virus can be used, making the candidate vaccines cheaper to manufacture and potentially lowering the risk of skewing the immune response to a more extracellular pathogen response.