Host cell components affect the sensitivity of HIV type 1 to complement-mediated virolysis.

ABSTRACT

An infection-competent, full-length HIV-1 clone (pNL4-3) was expressed in seven human cell lines and in peripheral blood mononuclear cells in order to assess the contribution of host cell components toward interaction of free virus with the complement system. HIV-1 expressed in the H9 cell line, which is frequently used for in vitro infection, was relatively susceptible to complement-mediated virolysis in the presence of both HIV antibody-positive patient serum and an anti-V3 monoclonal antibody. Expression of complement receptors 1, 2, and 3, complement control proteins membrane inhibitor of reactive lysis (MIRL, CD59) and decay-accelerating factor (DAF, CD55), and HLA-DR was assessed on host cells. There was an inverse relationship between the sensitivity of virus to complement and the amount of expression of MIRL and DAF on cells. HIV derived from the JY cell line and the mutant JY33 cell line, which is deficient in expression of phosphatidylinositol (PI)-linked proteins including MIRL and DAF, were also evaluated for complement-mediated virolysis. Virus expressed in the mutant cell line was more sensitive to antibody-independent as well as antibody-dependent complement-mediated virolysis than virus expressed in the wild-type cells. Direct demonstration of the presence of MIRL and DAF on the viral surface was obtained by showing that anti-MIRL or anti-DAF antibody induced complement-mediated virolysis. These experiments show that the host cell type can substantially influence the susceptibility of HIV to complement-mediated virolysis and suggest that PI-linked complement control proteins play an important role in this resistance.