SLC35A2 modulates paramyxovirus fusion events during infection

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Paramyxoviruses, including mumps virus (MuV), Newcastle disease virus (NDV), and Sendai virus (SeV), are significant human and animal pathogens.
• Knowledge of host factors governing paramyxovirus infection remains limited, hindering therapeutic development.

Purpose of the Study:

• To identify novel host factors essential for paramyxovirus infection using a loss-of-function CRISPR screen.
• To elucidate the specific roles of identified host factors in paramyxovirus entry, fusion, and spread.

Main Methods:

• A recombinant Sendai virus (SeV) expressing destabilized GFP (rSeVC^dseGFP) was employed in a genome-wide CRISPR loss-of-function screen.
• Knockout (KO) cell lines for identified genes (SLC35A1 and SLC35A2) were generated and analyzed for viral binding, entry, and fusion efficiency.
• Viral syncytia formation was assessed to evaluate cell-to-cell spread.

Main Results:

• The CMP-sialic acid transporter (CST) gene SLC35A1 and UDP-galactose transporter (UGT) gene SLC35A2 were identified as essential for paramyxovirus infection.
• SLC35A1 KO cells exhibited reduced binding and infection of SeV, NDV, and MuV due to the absence of sialic acids, known viral receptors.
• SLC35A2 KO cells revealed critical roles for the UGT in virus-cell and cell-to-cell fusion, with differential requirements for SeV, NDV, and MuV entry and syncytia formation.

Conclusions:

• Paramyxoviruses can infect cells lacking canonical sialic acid receptors, highlighting alternative entry mechanisms.
• The UDP-galactose transporter (UGT) plays a crucial role in facilitating paramyxovirus fusion events during viral entry and cell-to-cell spread.
• Findings provide new insights into host-pathogen interactions and potential targets for antiviral strategies against paramyxoviruses.