Covid-19 and Cell Line Models

Symptoms of SARS-CoV-2 virus infection (which causes Covid-19) range from mild to severe depending on the type of CoV-2 variants and the individual’s ability to overcome the infection. The mechanisms behind these clinical variables are largely unknown. Development of in vitro cell line models can help to recapture different aspects of CoV-2 infection, identify host factors for the entry of CoV-2 virus and factors contributing to the severity of the infection. We screened over 300 molecularly annotated normal and tumor cell lines for their utility as models for studying CoV-2 infection. We found the following:

  1. A small subset of tumor cell lines express ACE2, the host receptor for CoV-2 spike protein, which makes them susceptible to CoV-2 infection.

  2. Interferon pathway was activated in response to CoV-2 infection in some of the susceptible cell lines.

  3. Rates of CoV-2 infection in cell lines varied depending on CoV-2 variants, with Delta and Omicron having the highest infection rate.

  4. Some cell lines formed syncytia after CoV-2 infection, again depending on the variant, with Delta inducing the highest level of syncytia formation.

  5. Cell lines that express high level of TMPRSS2, a transmembrane serine protease that facilitates CoV-2 entrance in the cell, were most sensitive to the antiviral drug Camostat, while other cells were more sensitive to E64d, a cathepsin inhibitor.

Hence cell lines can recapture several aspects of CoV-2 infection and are important resources for the study of Covid-19.


Syncytia formation after CoV-2 infection

Syncytia formation after CoV-2 infection in cell line models
Lung tumor cell line H1435 and H324, and Vero-E6, a kidney cell line from green monkey were infected with the spike protein from three CoV-2 variants: Wild type variant (614G), Delta variant and Omicron BA.1. Bald virus which lacks the coding region for spike protein was used as a negative control. GFP signals indicate cells that were infected with the plasmid constructs. Orange arrows show syncytia formed by cell fusion in H1435 and Vero-E6 cells. Red arrows indicate single cells with no fusion.