HIV NUCLEAR IMPORT IS GOVERNED BY THE PHOSPHOTYROSINE-MEDIATED BINDING OF MATRIX TO THE CORE DOMAIN OF INTEGRASE

The karyophilic properties of the viral matrix (MA) protein govern HIV nuclear import in nondividing cells such as macrophages. A critical r egulator of this process is the C-terminal tyrosine phosphorylation of MA during virus maturation. Here, we reveal the mechanism of this phe nomenon, by demonstrating that tyrosine phosphorylation induces the bi nding of MA to integrase (IN). This leads to the incorporation of MA m olecules into virus cores, and subsequently into uncoated viral nucleo protein complexes. A direct interaction between tyrosine-phosphorylate d MA and the central domain of IN can be demonstrated in vitro. It is blocked by phosphotyrosine, indicating that IN recognizes the phosphor ylated C-terminal residue of MA. These results explain how the karyoph ilic potential of MA is conferred to the HIV nucleoprotein complex.