We have been studying interactions between human immunodeficiency virus- 1 (HIV-1) and its host cells using primary human peripheral blood mononuclear cells (PBMC) and monocytes/macrophages (M/M) by looking into cell response to HIV-1 infection as well as characteristics of HIV-1 replication in M/M. The results are summarized as follows: (1) Decrease in cytokine production by HIV-1-infected macrophages in response to LPS-mediated activation. The capacity of (M/M) infected with a HIV-1 isolate to produce several immunomodulating cytokines including interleukin-1alpha (IL-1alpha), IL-1~, tumor necrosis factor- alpha (TNF-alpha), IL-6, IL-8, and macrophage chemo-attractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1beta, TNF- alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1alpha, IL-1beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M; (2) Growth characteristics and biochemical properties of monocytotropic and T-cell tropic HIV-1 in primary cells. We studied and compared the growth characteristics and biochemical properties of a monocytotropic isolate HIV-1 ADA and a cell line adapted-laboratory strain HIV-1 MN. PBMC and M/M derived from a single donor were used and expression of viral components were monitored. ADA isolate, which has been serially passaged in M/M, was shown to display tropism for both M/M and PBMC's without apparent preference but with more rapid growth in PBMC's. In contrast, the MN strain appeared to be preferentially replicate in T-cell line and to a limited manner in PBMC's. The level of replication of the MN strain was lower than the ADA in PBMC's as monitored by the expression of p24, RT and gp120. Titration of the ADA progeny viruses derived from either M/M or PBMC reveals that the viruses attained dual tropism regardless of the host cell types that generated their parental stocks. The majority of p24, RT, gp120 and infectivity was found to be associated with pellets prepared by ultracentrifugation.
