Human parvovirus B19 small 11-kDa protein competitively disrupts Grb2-SOS interaction by to the N-Terminal SH3 domain of Grb2.

Human parvovirus B19 infects erythroid progenitor cells and inhibits erythropoiesis. The small 11-kDa (s11-kDa) protein of the virus interacts with the host adaptor Grb2 (growth factor receptor-bound protein 2) and suppresses downstream kinase phosphorylation to promote viral genome replication; however, the underlying mechanism remains unclear. Here, we show that s11-kDa competitively disrupts the Grb2-SOS (Son of Sevenless) interaction by binding to the N-terminal SH3 domain of Grb2. Structural modeling indicated that the proline-rich region of the s11-kDa protein engage Grb2 molecules, potentially generating a high-affinity interaction that blocks SOS binding. These findings revealed a sophisticated viral replication strategy mediated by a viral accessory protein.