Experiments and biosafety
The paper describing this study is Carr et al (2026). The measurements are all made using a pseudovirus-based deep mutational scanning system that was originally described in Dadonaite et al (2023).
A key aspect of this system is that it utilizes pseudotyped lentiviral virions that encode no viral genes other than the viral entry protein (in this case GPC). Pseudotyping is a widely used and safe method to study viral entry proteins, since the pseudoviruses can only undergo a single cycle of infection and therefore pose no risk of transmission or replication in humans or any other animals. For this reason, they provide a safe way to study mutations to proteins from even biosafety level 4 viruses (e.g., Junin virus GPC) at biosafety level 2.
All cell entry measurements were made using cells expressing the host receptor from vesper mice (the natural reservoir of Junin virus) because:
Junin virus naturally infects rodents, so using the rodent receptor would more accurately reflect the evolutionary pressures shaping GPC in nature.
Using the rodent receptor allows us to understand the mutational constraints on GPC in order to inform basic understanding and countermeasure design, but eliminates the potential for our experiments to create information hazards (e.g., mutations that enable better binding to human receptors)