Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Area of Science:

• Virology
• Molecular Biology
• Host-Pathogen Interactions

Background:

• Global health is threatened by respiratory and arthropod-borne viral infections.
• Lack of effective antivirals and vaccines necessitates novel therapeutic strategies.
• Targeting host proteins essential for viral replication but non-essential for host survival is a promising approach.

Purpose of the Study:

• To identify host proteins critical for the replication of diverse viral families.
• To investigate the role of the calcium pump SPCA1 in viral propagation.

Main Methods:

• Genome-wide knockout screen in human haploid cells.
• Assessed the requirement of identified host factors for viral infection.
• Investigated the mechanism of SPCA1's role in viral glycoprotein maturation.

Main Results:

• The calcium pump SPCA1 (Secretory Pathway Calcium ATPase 1) was identified as essential for viruses in the Paramyxoviridae, Flaviviridae, and Togaviridae families.
• SPCA1 is required for the spread of measles, dengue, West Nile, Zika, and chikungunya viruses.
• SPCA1 regulates calcium-dependent proteases in the trans-Golgi network, crucial for viral glycoprotein maturation and subsequent viral spread.

Conclusions:

• SPCA1 is a critical host factor supporting the replication of a broad spectrum of RNA viruses.
• The calcium transport activity of SPCA1 is essential for viral glycoprotein processing.
• SPCA1 represents a potential broad-spectrum antiviral host target for combating established and emerging viral diseases.