Plasmas from Lymphocyte- and Macrophage-Tropic SIVmac-Infected Macaques Have Antibodies with a Broader Spectrum of Virus Neutralization Activity in Macrophage versus Lymphocyte Cultures

Abstract

AbstractWe examined plasma from macaques infected with three different phenotypes of SIVmacfor their ability to neutralize the infectivity of homologous and heterologous virus in lymphocyte (CEMx174 cells or normal rhesus macaque peripheral blood lymphocytes) or normal rhesus macaque macrophage (Mφ) cultures. Similar to previous findings, we observed that some plasmas failed to neutralize or poorly neutralized the infectivity of SIVmac239 and SIVmac251(<1:20 plasma dilution) in lymphocyte cultures. In contrast, when primary rhesus Mφ cultures were used as the indicator cells, the same plasmas neutralized both viruses at high dilutions (1:200 to 1:20,000). Neutralization of virus infectivity by the various plasmas was confirmed by SIV core antigen capture assays. We excluded the possibility that this differential neutralization in Mφ was related to the differences in the ability of the virus strain to replicate in these two cell types by demonstrating that the replication efficiency of SIVmac251 in CEMx174 cells, PBMC, and Mφ cultures was very similar. The role of Fc receptors on the Mφ surface in the clearance of the virus–antibody complexes was also excluded since similar neutralizing results were obtained using whole plasmas, purified IgG antibodies, and purified Fab fragments derived from the IgG fraction of these plasmas. The mechanism of virus neutralization in Mφ does not appear to involve blocking of virus entry into the cells since radiolabeled virus reacted with anti-SIV antibodies was taken up by rhesus Mφ as efficiently as virus reacted with normal antibody. DNA of the neutralized virus was identified in the Mφ cultures, but virus replication, as evidenced by accumulation of viral protein products, was not detectable so long as the antibodies were present in the medium. Removal of the antibodies resulted in a resumption of virus replication in the Mφ. These results indicate that virus infectivity can be efficiently neutralized by antibodies in Mφ cultures by a mechanism that is fundamentally different from that in lymphocyte cultures