PLASMAS FROM LYMPHOCYTE-TROPIC AND MACROPHAGE-TROPIC SIVMAC-INFECTED MACAQUES HAVE ANTIBODIES WITH A BROADER SPECTRUM OF VIRUS NEUTRALIZATION ACTIVITY IN MACROPHAGE VERSUS LYMPHOCYTE-CULTURES

We examined plasma from macaques infected with three different phenoty pes of SIVmac for their ability to neutralize the infectivity of homol ogous and heterologous virus in lymphocyte (CEMx174 cells or normal rh esus macaque peripheral blood lymphocytes) or normal rhesus macaque ma crophage (M phi) cultures. Similar to previous findings, we observed t hat some plasmas failed to neutralize or poorly neutralized the infect ivity of SIV(mac)239 and SIV(mac)251(<1:20 plasma dilution) in lymphoc yte cultures. In contrast, when primary rhesus M phi cultures were use d as the indicator cells, the same plasmas neutralized both viruses at high dilutions (1:200 to 1:20,000). Neutralization of virus infectivi ty by the various plasmas was confirmed by SIV core antigen capture as says. We excluded the possibility that this differential neutralizatio n in M phi 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 SIV(mac)251 in CEMx174 cells, PBMC, and M ph i cultures was very similar. The role of Fe receptors on the M phi sur face in the clearance of the virus-antibody complexes was also exclude d 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 M phi does not appear to involve blocking of virus entry into the c ells since radiolabeled virus reacted with anti-SIV antibodies was tak en up by rhesus M phi as efficiently as virus reacted with normal anti body DNA of the neutralized virus was identified in the M phi cultures , but virus replication, as evidenced by accumulation of viral protein products, was not detectable so long as the antibodies were present i n the medium. Removal of the antibodies resulted in a resumption of vi rus replication in the M phi. These results indicate that virus infect ivity can be efficiently neutralized by antibodies in M phi cultures b y a mechanism that is fundamentally different from that in lymphocyte cultures. (C) 1997 Aademic Press