Manganese Mediates Its Antiviral Functions in a cGAS-STING Pathway Independent Manner

Area of Science:

• * Virology
• * Immunology
• * Biochemistry

Background:

• * The innate immune system is crucial for detecting viral infections.
• * Manganese (Mn) activates the DNA-sensing cGAS-STING pathway, enhancing anti-DNA virus defenses.
• * The role of Mn²⁺ in combating RNA viruses and its precise mechanism remain unclear.

Purpose of the Study:

• * To investigate the antiviral effects of manganese (Mn²⁺) against a range of viruses, including RNA and DNA types.
• * To elucidate the role of the cGAS-STING signaling pathway in Mn²⁺-mediated antiviral activity.
• * To explore potential redundant mechanisms in Mn²⁺'s antiviral functions.

Main Methods:

• * Dose-dependent antiviral assays were performed using various animal and human viruses (e.g., PRRSVs, VSV, HSV1).
• * CRISPR-Cas9 technology was employed to create cGAS and STING knockout cell lines.
• * Antiviral activity and cGAS-STING pathway activation were assessed in both wild-type and knockout cells.

Main Results:

• * Mn²⁺ demonstrated dose-dependent antiviral effects against both RNA and DNA viruses.
• * Knockout of cGAS or STING did not impair Mn²⁺'s antiviral functions.
• * Mn²⁺ was confirmed to promote the activation of the cGAS-STING signaling pathway.

Conclusions:

• * Mn²⁺ exhibits broad-spectrum antiviral activity through a mechanism independent of the cGAS-STING pathway.
• * Redundant pathways contribute to Mn²⁺'s antiviral capabilities, suggesting complex host-pathogen interactions.
• * Mn²⁺ presents a promising therapeutic target for developing novel antiviral treatments.