SARS-CoV-2 infection: resistance is futile

In a recent paper in the Journal of Virology, PhD candidate Nic Gracie and Associate Professor Tim Newsome from the School of Life and Environmental Sciences  (SoLES) show that the SARS-CoV-2 Spike protein, which allows the virus to enter cells, also acts to potently suppress immune defences.

Nic Gracie has long been intrigued by the TGF-beta cytokine, a cellular signalling molecule that has its hands in many cellular processes, and is also a marker of severe disease in COVID-19 patients. Securing seed funding from Sydney ID enabled him to identify a major pathway how SARS-CoV-2 regulates TGF-beta during viral infection.

This study required Nic to assemble a team of Sydney ID researchers - including Dr Megan Steain and Professor Joel Mackay - as well as collaborators at UTS and the Kirby Institute at UNSW, to put all the pieces of the puzzle together. He discovered that integrin complexes were the missing link. When SARS-CoV-2 alights on the surface of a cell, an interaction with cell adhesion molecules, integrins, leads cells to induce expression of TGF-beta. This activity was then mapped to a highly conserved region of Spike protein of just a few amino acids. Given the many functions that TGF-beta is implicated in, this new activity of Spike is likely to have many consequences on infection. The first place they looked was immune suppression and they discovered cellular immune defences were suppressed by Spike. 

SARS-CoV-2 is not the only virus to engage integrins, and this study provides further support to focus on integrins as possible targets to treat infectious diseases.