High levels of viremia are often found to be associated with acute HIV-1 infection. However, the cell types and tissue of organs which contributed to the virus load remain unclear. We believe that lymphoreticular system such as liver and spleen is the source of the viremia, since viruses isolated from individuals' peripheral blood mononuclear cells (PBMC) or blood-derived macrophages (MDM's) before seroconversoins or in early phases of AIDS were predominantly macrophage-tropic and this cell type is known to be the most abundant in these organs. We therefore study the in vivo permissiveness to the infection of HIV-1's of primary cells isolated from spleen and liver in order to determine whether these organs may potentially constitute the major source of acute viremia. From these studies, we found that the viruses we have tested can be grouped into three categories: 1) Highly amphitropic primary isolates such as HIV-1 ADA which grew in both splenocytes and splenic/hepatic macrophages comparable to MDM's; 2) Highly lymphotropic primary isolates such as HIV-1 Mr452 which grew only in splenocytes but restricted in macrophages; and, 3) Lab-adapted strains which grew transiently (HIV-1 CC and HIV-1 MN) or only at low-levels (HIV-1RF and HIV-1(HXB3) in splenic/hepatic macrophages, also comparable to MDM's. These results suggest that high levels of acute viremia are generated primarily in the spleen and liver, and these organs may play a critical role in pathogenesis of HIV-1 infection. Other settings, such as physiological micro-environments, may influence the biology of the interations between virus and host cells. We tested possible effects of physiological levels of human plasma on the HIV-1 infectivity. We found plasma enhances the infectivity of HIV-1 primary isolates in both PHA-stimulated PBMC and MDM's. Enhancement required plasma to be present during the virus-cell incubation and resulted in a 3- to 30- fold increases in virus titers in all four primary isolates. Physiological concentrations of human plasma appear to recruit additional infectivity thus resetting the infectious potential of the virus innnoculum. Since recent studies demonstrate that chemokine receptors play important roles in cellular tropism, we will be studying the possible roles of these receptors in differential permissiveness of splenocytes, Kupffer's cells and MDM to infection and plasma enhancing effects.
