Plscr1-flox Mouse

Plscr1, short for phospholipid scramblase 1, is a protein-coding gene. It has diverse functions and is involved in multiple biological processes. It is known to play a role in maintaining the asymmetric phospholipid distribution in cell membranes. Also, it is associated with interferon-mediated antiviral responses, which is of great importance in host innate immunity against viral infections [3].

In the context of viral infections, Plscr1 has been identified as a key factor. In genome-wide CRISPR-Cas9 screens, IFNγ-induced Plscr1 restricted live SARS-CoV-2 infection, including against the Delta and Omicron lineages, and its activity extended to other highly pathogenic coronaviruses [1]. It directly targeted SARS-CoV-2-containing vesicles to prevent spike-mediated fusion and viral escape [1]. In influenza A virus infection, Plscr1-/-mice were more susceptible to H1N1 SIV infection, indicating its role in antiviral defense in vivo [2]. Regarding human cytomegalovirus (HCMV), HCMV plaque formation and replication were significantly higher in Plscr1-knockout cells, suggesting that Plscr1 negatively regulates HCMV replication [3]. In SARS-CoV-2 infection, Plscr1 inhibits viral entry by downregulating plasma membrane expression of ACE2 [4]. A genome-wide arrayed CRISPR screen showed that Plscr1 specifically restricts spike-mediated SARS-CoV-2 entry, mainly the endocytic entry route, and recent SARS-CoV-2 variants have adapted to bypass this restriction [5].

In conclusion, Plscr1 is essential in host antiviral defense. Through gene knockout studies in mouse models, its role in restricting infections of various viruses like SARS-CoV-2, influenza A virus, and HCMV has been clearly demonstrated. These findings contribute to understanding the mechanisms of host-virus interactions and may provide potential targets for antiviral therapies.