The recurrent Spike A222V mutation in SARS-CoV-2 enhances replication in primary deer lung cells

Area of Science:

• Virology
• Evolutionary Biology
• One Health

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat within a One Health framework due to its ability to infect both humans and animals.
• Identifying mutations that allow viral adaptation to animal hosts is crucial for preventing persistent animal reservoirs and subsequent human spillover events.

Purpose of the Study:

• To identify and characterize SARS-CoV-2 mutations that adapt to animal hosts using experimental evolution and epidemiological data.
• To determine the impact of identified mutations on viral replication in both human and animal cells.

Main Methods:

• SARS-CoV-2 was passaged in cells expressing ACE2 receptors from humans, dogs, cats, mink, and white-tailed deer.
• Sequencing of passaged viral populations to identify adaptive mutations.
• Analysis of SARS-CoV-2 sequences for convergent evolution patterns in human and animal-derived strains.
• Construction and replication assessment of SARS-CoV-2 variants (Spike A222V) in human and animal lung cells.

Main Results:

• The Spike A222V mutation, identified in cat ACE2 expressing cells, was also found convergently in human and animal SARS-CoV-2 sequences.
• SARS-CoV-2 with Spike A222V replicated similarly to wild-type in human lung cells but showed enhanced replication in deer lung cells, independent of the deer ACE2 receptor.
• Infection via human, dog, cat, and mink ACE2 receptors resulted in reduced replication of the Spike A222V variant.

Conclusions:

• Spike A222V is a putatively deer-adaptive mutation.
• Further research is needed to assess the relevance of Spike A222V to transmission within deer and to other susceptible animal species.