Induction of beta interferon by human immunodeficiency virus type 1 and its gp120 protein in human monocytes-macrophages: role of beta interferon in restriction of virus replication

Abstract

In vitro cultivated human monocytes show a time-dependent differentiation into macrophages, characterized by an increased expression of macrophage-specific antigens. Monocytes-macrophages were infected with human immunodeficiency virus type 1 strain Ba-L (H1V-lBaL) at different stages of differentiation. When 7-day cultured macrophages were infected in the presence of antibodies to beta interferon (IFN-,B), a significant increase in HIV-1 p24 release was detected. This effect was not observed in 1-day monocytes. This finding suggests that IFN-, secreted by the infected macrophages inhibits p24 release. Treatment of cultured macrophages with recombinant gpl20 (rgpl20) protein resulted in the induction of IFN-13 mRNA and in an antiviral state to vesicular stomatitis virus. This rgpl20-induced antiviral state was largely neutralized by antibodies to IFN-13, whereas anti-IFN-a antibodies were ineffective. In cultured macrophages, 0.1 IU of IFN-P per ml was sufficient to induce a marked inhibition of vesicular stomatitis virus yield, whereas this dose was ineffective in 1-day monocytes. These results indicate that (i) HIV-1 (possibly in part through its gpl20 protein) induces low levels of IFN-0 in macrophages and (ii) this IFN-, is very effective in inducing an antiviral state in differentiated macrophages.

Monocyte/macrophage-derived CC chemokines and their modulation by HIV-1 and cytokines: A complex network of interactions influencing viral replication and AIDS pathogenesis

“…Hypothetical model illustrating the effects of early interactions between macrophages and HIV-1 surface components leading to CC chemokine production and their role in the pathogenesis of AIDS. The model mostly reflects the results obtained by our group [12,17,37]. Other non-CC chemokines induced by HIV infection as well as by viral components may play additional roles in the control of viral replication, spreading, and pathogenesis.…”

“…Finally, HIV-1 infection of monocytes/macrophages also results in the production of type I interferons (IFNs). In particular, we reported that HIV infection leads to the secretion of low levels of IFN-␤, which is very effective in restricting viral replication in monocyte-derived macrophages (MDM) but not in freshly isolated monocytes [12]. The HIV-mediated induction of cytokine expression does not necessarily require productive infection of monocytes/macrophages as, at least for some cytokines (IFN-␤ and IL-10), secretion can be observed upon exposure of these cells to HIV-1 surface components, such as gp120 [12,13].…”

“…In particular, we reported that HIV infection leads to the secretion of low levels of IFN-␤, which is very effective in restricting viral replication in monocyte-derived macrophages (MDM) but not in freshly isolated monocytes [12]. The HIV-mediated induction of cytokine expression does not necessarily require productive infection of monocytes/macrophages as, at least for some cytokines (IFN-␤ and IL-10), secretion can be observed upon exposure of these cells to HIV-1 surface components, such as gp120 [12,13]. Chemokines have become the focus of intense investigation since the discovery that at least some of their receptors function as coreceptors for HIV entry into target cells [14].…”

Role of interferons and other cytokines in the regulation of the immune response

“…For instance, when studying the cytokine response to LPS in freshly isolated monocytes and in monocyte-derived macrophages (after 7 days of culture), we found that considerably more TNF-a and IL-6 were produced by in vitro cultured differentiated macrophages than by freshly seeded monocytes (55). We also found that in vitro differentiation of monocytes into macrophages enables them to respond to LPS through the production of IFN-/3 and to acquire a higher sensitivity to type I IFN compared to monocytes (54).…”

Acceleration of R5 HIV replication by polymorphonuclear neutrophils in cultures of macrophages

“…The attached monocytes were maintained in culture for 7 days to allow differentiation into MDM with RPMI-1640 medium, supplemented with 10% heat-inactivated human AB serum (Sigma-Aldrich, St Louis, MO, USA), 2 mM L-glutamine and antibiotics, and then used for HIV infection. [33][34][35][36] At the time of MDM infection with R5 HIV, PMN were isolated again from peripheral blood syngeneic to the monocyte donor by Ficoll-Hypaque and dextran sedimentations. 37 Thus, after the Ficoll-Hypaque sedimentation of whole blood, precipitates were obtained as a PMN-rich fraction.…”