Recent virus locatilization and turnover studies in vivo indicate that activated peripheral blood mononuclear cells (PBMC) and blood monocyte- derived macrophages (MDM) in general may be the major target cells in vivo of the virus. We therefore quantitatively and qualitatively characterized the initial lag, log-growth, and stationary phase kinetics of a dual-tropic primary HIV-1 in both MDMs and PBMCs in terms of various biological and bio-physicochemical parameters. By the use of an autologous donor cell assay, a kinetic wash-out experimental format and particle separation techniques, the parameters that have been determined include viral replication kinetics, viral production rate per cell, soluble and virion-associated virus-encoded gene products (such as gp120 concentrations, RT, and p24), the numbers and stability of gp120 molecules associated with a virion, the ratios of infectious to noninfectious virus particles and reciprocal infectivity/tropism. These new insights should be useful for future studies aimed at characterization of primary clinical isolates of HIV-1 and further our understanding of how they may impact on the disease process itself. Furthermore, we believe that lymphoreticular systems such as the liver and spleen are the major sources of the acute viremia. We also studied the in vitro permissiveness of splenic and hepatic organ-based lymphoid cells for infection with HIV-1. The unstimulated, unseparated splenic mononuclear cells (SMCs) are highly susceptible to the primary isolates that are either dual/macrophage tropic or lymphotropic, whereas both splenic and hepatic adherent cells (presumably of macrophage lineage) are highly permissive for dual/macrophage-tropic isolates and refractory to lymphocytotropic isolates. As the spleen may play a unique and central role in viral replication and/or control during infection with HIV-1 and, given the interesting cellular characteristics, availability and cryopreservability of spleen cells, the organ-based SMC cell system appears to be another in vitro tool for further study of organ-specific and virus-cell-specific interactions. All together, these cell culture systems should also allow for additional study of the role of the chemokine coreceptor family of cell surface molecules involved in HIV-1 entry.
