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 Cell 2023), and that they can also encode proteins dedicated to canceling specific defense systems (Leavitt Nature 2022; Hobbs Nature 2022; Yirmiya Nature 2024; Antine Nature 2024; Yirmiya Cell 2025). 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 Nature 2022; Yirmiya 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 reproduce in infected cells (Osterman Nature 2024). We developed AI-based computational approaches that can discover virus-encoded inhibitors of host immunity in a large-scale, unbiased manner (Yirmiya et al, Cell 2025).

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).