To evade the human host's immune response, SARS-CoV-2, the coronavirus that causes COVID-19 uses the machinery of defense cells to induce the expression of unproductive isoforms of key antiviral genes—variant forms of genes that result from disrupted splicing or transcription processes and do not code for functional (protective) proteins. This is a key finding of a study conducted by researchers at the Albert Einstein Jewish Brazilian Hospital (HIAE), the University of São Paulo (USP) and the Federal University of Minas Gerais (UFMG). The study, which offers a foundation for the development of novel therapeutic strategies to combat COVID-19, is in the .
Other viruses, including coronaviruses, also distort protein production by disrupting messenger RNA (mRNA) splicing, but SARS-CoV-2 goes further by blocking expression of interferons, a family of proteins that help the immune system fight infection, and modulating specific immune cells. A lack of precise details regarding this process has been a major hindrance to the development of novel options to treat COVID-19. In the study, the researchers set out to confirm the hypothesis suggested in the scientific literature that production of unstable mRNA isoforms can give rise to non-functional proteins.
To do this, they conducted an integrative analysis that combined several transcriptomic and proteomic datasets to arrive at a detailed characterization of the infected host cell landscape, both in vitro and in vivo. They found t.