Glycosylphosphatidylinositol deficiency attenuates the production of infectious HIV-1 and renders the virions sensitive to complement attack (VIR1P.1128)

Abstract

Abstract Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated destruction by incorporating regulators of complement activation (RCA) from the host cells. Abrogation of RCA function leads to complement-mediated virolysis. However, little is known about the mechanism by which HIV-1 incorporates RCA from the host cell. Here we used glycosylphosphatidylinositol (GPI)-deficient Jurkat (Jurkat-7) cells that only express intracellular CD59 (a key member of RCA), but not on the surface, to study how HIV-1 incorporates CD59 from an infected cell. Compared to wild type Jurkat cells, Jurkat-7 cells are less susceptible to HIV-1 infection, and produces lower amount of virions due to the impaired GPI biosynthesis. Interestingly, virions produced from Jurkat-7 cells did not contain CD59, while virions from wild-type Jurkat cells did contain CD59 with a certain amount of viral protein expression. This indicates that HIV-1 incorporates CD59 from the surface of host cell rather than from the intracellular compartments. Virions produced from Jurkat-7 cells are less infectious, but more susceptible to complement-mediated virolysis due to the failed CD59 incorporation into the virus surface. Furthermore, transient restoration of GPI anchor in Jurkat-7 cells resulted in recovered surface expression of CD59. These results reveal a critical role of GPI anchor and GPI-anchored proteins in HIV-1 life cycle and incorporation of CD59, probably other host cell proteins into the HIV-1 virions.