Molecular & cellular virology of coronaviruses

Coronaviruses are large positive-strand RNA viruses belonging to the Coronaviridae family. They encompass more than 25 species infecting humans and a broad range of animal species. Human coronaviruses are responsible for many cases of seasonal common cold, whose economic and social impact is probably underestimated. Moreover, the human coronaviruses that are usually associated with mild diseases can cause severe respiratory tract infections in fragile populations (newborn babies, elderly and immunocompromised people). Animal coronaviruses are often highly infectious and responsible mostly for enteric and respiratory diseases in livestock and domestic animals. Their high mortality rates result in a significant global economic burden. But altogether, until 2003, coronaviruses were not considered as a major human health threat. The situation changed since then, with the emergence of two highly pathogenic coronaviruses, namely SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle-East respiratory syndrome coronavirus). These two highly pathogenic coronaviruses have emerged from zoonotic reservoirs, and they often cause lethal respiratory infections in humans. The recent identification of other coronaviruses in bats suggests that other viruses from this family could also emerge as novel human pathogens. In the absence of specific treatment, it is essential to better understand how such viruses exploit the cellular machinery for their propagation. Our current objectives are (i) to investigate the mechanisms of entry and assembly of coronaviruses with a special focus of MERS-CoV and (ii) to identify novel host factors involved in the infectious cycle of coronaviruses. Besides a better understanding of coronavirus life cycles, this research program could also lead to the identification of novel antiviral targets.