How viruses overcome host immunity

Given the complexity of the bacterial immune system, we are now interested to find how phages can overcome bacterial defenses. We found that phages can passively evolve to escape bacterial defense systems (Stokar-Avihail et al Cell 2023), and that they can also encode proteins dedicated to canceling specific defense systems (Leavitt et al, Nature 2022; Hobbs et al, Nature 2022; Yirmiya et al, Nature 2024; Antine Nature 2024). Our discoveries include new concepts in antiviral evasion from immunity, for example we found that phages produce “sponge” proteins that tightly bind and sequester immune signaling molecules, thus blocking signaling-based immune systems (Leavitt et al, Nature 2022; Yirmiya et al, Nature 2024). We also found that when bacteria deliberately eliminate essential molecules in attempt to slow down phage infection, some phages can re-build these molecules and successfully infect (Osterman et al, Nature 2024).

Schematic depiction of the proteins mutated in phages that escape bacterial anti-phage systems, as well as selected examples from previous studies (marked with an asterisk). Phage proteins are depicted as colored shapes and text and defense systems in black text (Figure from: Stokar-Avihail et al, Cell 2023).