TIP47 is Required for the Production of Infectious HIV-1 Particles from Primary Macrophages

Abstract

Macrophages are among the major targets of HIV-1 infection and play a key role in viral pathogenesis. Identification of the cellular cofactors involved in the production of infectious HIV-1 from macrophages is thus crucial. Here, we investigated the role of the cellular cofactor TIP47 in HIV-1 morphogenesis in primary macrophages. Using siRNA approach, we show that TIP47 is essential for HIV-1 infectivity and propagation. TIP47 silencing disrupts Gag and Env colocalization in macrophages. Moreover, mutations in HIV-1 Gag or Env, which abolish interaction with TIP47, impair HIV-1 propagation and infectivity preventing colocalization of Gag and Env, Gag and Env coimmunoprecipitation. Interestingly, disruption of Gag-TIP47 interaction by matrix mutation or TIP47 depletion also causes Gag to localize in scattered dots in the vicinity of the plasma membrane of macrophages. Therefore, TIP47 is required for the encounter between Gag and Env, and thus for the generation of infectious HIV-1 particles from primary macrophages.