To overcome the anti-viral effects mediated by type I interferon-induced restriction factors, HIV-1 have evolutionarily acquired viral antagonists. For instance, tetherin (also known as BST2), a well-known protein restricting HIV-1 replication, exerts anti-HIV-1 effect by anchoring released progeny virions on the cell surface, whereas viral protein U (Vpu), an HIV-1-encoding accessory protein, antagonizes the anti-viral action mediated by tetherin. However, its precise role in HIV-1 replication in vivo remains unclear. Here we use a hematopoietic stem cell-transplanted humanized mouse model and several vpu mutants specifically lacking its function and demonstrate that anti-tetherin ability of Vpu is a prerequisite for efficient viral spread during the initial phase of infection. Our results suggest that tetherin is an important intrinsic effector restricting HIV-1 replication in vivo, while Vpu is a key factor to ensure efficient viral spread during the initial phase of infection by antagonizing tetherin.
Furthermore, by using HIV-1-infected humanized mouse model, we have recently launched a new approach to investigate the dynamics of HIV-1 infection through omics analyses. We would like to introduce our recent findings and discuss about them.