Are bats evolving more potent antiviral immune systems? Investigating the evolution and antiviral capacity of SERINC3 in Rhinolophus bats

Bats are an incredibly diverse and abundant viral reservoir species. Their immune systems are uniquely anti-inflammatory and anti-viral, often tolerating viral infection without any signs of disease. Several pandemic and emerging viruses have been traced back to different bat species, including SARS-CoV-2, SARS, Ebola virus and Nipah virus. Genetic positive selection analysis conducted in a recent study has revealed a pattern of antiviral immune genes under positive selection across various bat species. One of these genes is the antiviral restriction factor SERINC3. The SERINC protein family is a collection of transmembrane proteins conserved amongst mammals. SERINC3 and SERINC5 are members of this family that have previously been shown to inhibit viral infectivity in multiple viruses such as SARS-CoV-2, Murine Leukemia Virus, Influenza A and HIV-1. Typically, SERINC5 is the more potent restriction factor, with SERINC3 having an attenuated or absent effect. This study investigates if SERINC3 has evolved to be a more active restriction factor in bat species where it is under positive selection. Using lentiviral pseudotypes or SARS-CoV-2 and Murine Leukemia Virus, SERINC3 alleles from Rhinolophus affinis and Rhinolophus sinicus were cloned and assayed relative to human SERINC3 and SERINC5. Additionally, further positive selection analysis will also be used to identify if there are specific amino acid residues under selection in SERINC3. We show the first case of enhanced SERINC3 antiviral activity in another species, with Rhinolophidae SERINC3 acting restricting SARS-CoV-2. Additionally, our positive selection analysis identified the transmembrane helices, extracellular loop 4, and 6 residues in SERINC3 to be possible functional regions and target for future analysis. The results of this study will help give insight into the bat immune system and how bats tolerate chronic viral infection. Understanding these factors can be used to understand the limits to viral spillover events from bats which can be a parameter in pandemic spread.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

2025

Author dc:creator

• Loizidou, Erin

Advisors dc:contributor.advisor

• Sloan, Richard
• Picozzi, Kim

• SERINC3
• Antiviral
• Positive selection
• Rhinolophus bats
• Viral reservoir

Language dc:language.iso

en

Identifier URI

http://dx.doi.org/10.7488/era/6108

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/43574