Popularization of research advances on COVID-19

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Which cellular proteins interact with the viral genome?

The process of cell infection by a virus is complex and involves several stages usually specific to the virus. A virus attaches itself to the host-cell and penetrates the cytoplasm using a cellular receptor, ACE2 in the case of SARS-CoV-2. Once its genetic material is inside the cell (RNA for SARS-CoV-2), it hijacks and mobilizes host cell mechanisms to produce new virions. RNA and viral proteins interact with the cell to facilitate the viral cycle.

Researchers at the Universities of Stanford and New Haven in the USA have recently identified those cellular proteins that interact with viral RNA. These proteins could protect cells against viral aggression.

The scientists first of all identified the proteins from the host interacting with the 30,000-base RNA genome of the virus. To do this they used 2 cell-model lines of SARS-CoV-2 infection (Huh7.5, human hepatocyte cells, and VeroE6, monkey kidney cells) 24 to 48 hours after infection. They discovered 309 proteins with various functions. These proteins are more abundant after 24 hours, which could suggest they play a more important role during the early stages of viral genome replication. The vast majority of host proteins identified in these 2 cell-model lines were also identified in primary human lung cells. For example, we find proteins involved in the cell’s translation mechanism (for the production of proteins). Indeed, one of the first steps in the viral cycle is the translation of the viral genome into proteins. For this, the virus hijacks the host’s mechanisms for the manufacture of its own proteins.

The researchers then studied the function of these different cellular proteins. The majority are involved in defense against infection by SARS-CoV-2 (anti-viral function) or in cell protection (cellular survival). Lastly, they noted an connection between the mitochondria and the RNA of SARS-CoV-2. These organelles may therefore have an antiviral function.

In conclusion, these results allow the identification of a certain number of host proteins interacting with the viral RNA genome. Some of them are similar to those involved in other infections, others are specific to SARS-CoV-2. These proteins may enable the invention of new treatments.

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