COV RESTRIC · Unravelling species barriers of coronaviruses

Unravelling species barriers of coronaviruses

Coronavirus (CoV) infections can pose a significant global health threat due to the emergence of highly pathogenic variants, like the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and more recently the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which emerged during cross-species transmissions from animals to humans. One hallmark of these two highly pathogenic viruses, SARS-CoV and MERS-CoV, is that they arose through zoonotic transmissions. Although the first cross-species transmission of SARS-CoV to the human population was mediated by civet cats from live animal markets in Guangdong, China in 2002, the viral reservoir has later been traced back to horseshoe bats. A sustained human-to-human transmission was the primary cause for the human epidemic, which led to total of 8437 infected people and 813 SARS-related deaths worldwide. Immediate and effective public health measures contained the outbreak by 2003 and, as of today, the virus has been declared eradicated. In contrast, MERS-CoV emerged in Middle Eastern countries in 2012 and has so far caused 2458 infections with a fatality rate of approximately 35 % of reported patients. Dromedary camels have been identified as the primary host for transmission of the virus to humans, however bats are speculated as the ancestral host reservoir. In comparison to SARS-CoV, MERS-CoV spillover from dromedary camels to humans is constantly ongoing as the virus is circulating in this camelid population. The precise mechanisms that allow coronaviruses to jump across species barriers still remain elusive. Therefore, studies addressing viral control mechanisms precluding transmission across species barriers are of utmost importance to ultimately contribute to the prevention of zoonotic infections. We hypothesized that conserved restriction factors exists between different species which limit viral replication and which need to be overcome via viral evasion and adaptation strategies in order to establish a zoonotic infection. We proposed a genetic screening approach in combination with state-of-the-art technologies to identify unknown coronavirus restriction factors, restricting replication of different coronavirus variants originating from different hosts, including the highly pathogenic human SARS-CoV and MERS-CoV. We specifically aimed to identify interferon stimulated genes (ISGs) that are conserved between different species. The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of ISGs, some of which encode direct antiviral effectors that could act as viral restriction factors. Upon application of an ISG screening approach we could identify a novel ISG, namely lymphocyte antigen 6 complex, locus E (LY6E) that potently restricts human CoVs (Figure 1). We analyzed its mechanism of action and further characterized the role of this ISG in the CoV replication cycle. In conclusion, we provide novel knowledge about innate CoV restriction factors. A deeper understanding of viral restriction could in the end lead to novel therapeutic options against emerging CoVs.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз