STING single amino acid polymorphisms modulate iridovirus immune evasion and pathogenicity spectrum

Area of Science:

• Virology
• Immunology
• Evolutionary Biology

Background:

• Host-virus coevolution drives viral immune evasion and pathogenicity.
• Mechanisms underlying viral cross-species pathogenicity shifts are not fully understood.

Purpose of the Study:

• Investigate the role of single amino acid polymorphisms (SAPs) in host stimulator of interferon genes (STING) in modulating viral immune evasion and pathogenicity.
• Determine how ISKNV interacts with STING from different fish species.

Main Methods:

• Identified specific residues in mandarin fish STING targeted by ISKNV protein VP012R.
• Analyzed the impact of STING polymorphisms (K315/R315) on viral immune evasion and pathogenicity.
• Conducted phylogenetic analysis to correlate STING variants with host mortality rates.

Main Results:

• ISKNV VP012R targets mandarin fish STING at C196 and K315, promoting degradation and suppressing interferon responses.
• The K315/R315 STING polymorphism acts as a molecular switch: K315 allows viral immune evasion and STING degradation in susceptible hosts, while R315 maintains STING stability in resistant hosts.
• Phylogenetic analysis revealed a correlation between the K315 variant and high host mortality (≥50% lethality), versus the R315 variant in resistant hosts (≤25% lethality).

Conclusions:

• Host protein SAPs can modulate the pathogenicity spectrum of viruses like ISKNV.
• STING polymorphisms are key determinants of viral immune evasion and cross-species pathogenicity.
• These findings enhance understanding of host-virus coevolution and biological diversity.