Macrophages are required for influenza virus infection of human lymphocytes.

Abstract

Monocyte and lymphocyte surface-expressed viral antigens have been demonstrated after exposure of unseparated human mononuclear leukocytes to influenza virus in vitro. The current studies, using [35S]methionine pulse-labeled purified preparations of virus-exposed macrophages, depleted of lymphocytes, demonstrate that the presence of these viral proteins does represent new synthesis. However, purified lymphocytes, depleted of monocytes-macrophages and exposed to influenza virus, showed no detectable viral protein synthesis. In further experiments, unseparated mononuclear leukocytes were exposed to virus and subsequently separated by countercurrent centrifugal elutriation. Both macrophages and lymphocytes were then shown to synthesize influenza proteins. Cell-free control or influenza virus-infected macrophage-derived supernatant fluids did not facilitate influenza virus infection of the lymphocytes. The data suggest that macrophages are required for influenza virus infection of human lymphocytes, and raise the possibility that macrophage facilitation of an abortive infection of lymphocytes plays a role in the generation of effective immunity to viral antigens.

Suppressed expression of ICAM-1 and LFA-1 and abrogation of leukocyte collaboration after exposure of human mononuclear leukocytes to respiratory syncytial virus in vitro. Comparison with exposure to influenza virus.

“…MNL exposed to inactivated RSV produce net IL-l activity and proliferate, just as do MNL exposed to infectious or inactivated influenza virus (17,19,34). Influenza virus infection of peripheral blood MNL appears to be abortive, with production of viral proteins but without release of free progeny virus (2,28,35). The occasional detection of RSV in culture fluids has been associated with MNL subpopulations that did not produce net IL-1 inhibitor activity in our studies, and not with monocyte-macrophage or lymphocyte populations that produced the inhibitory factor, even though producer and nonproducer populations of cells were both infected as determined by synthesis and expression of RSV F and G proteins (17,27).…”

“…The differences in production of IL-and IL-I inhibitors, and in cell-cell collaboration, are evident as early as synthesis and expression of influenza virus proteins are detected (2) and long before synthesis and expression of RSV proteins are detected (27). The differences in production of cytokines and cell-cell interactions persist even after RSV protein synthesis and expression are clearly detected, and after influenza virus protein synthesis is no longer detectable (2,17,28). The differences in response are so rapidly apparent that they are unlikely to be due to any delayed effect of RSV on host cell functions, although such effects also could exist.…”

“…immunological responses (1)(2)(3)(4). This interaction is thought to consist of both a specific signal, namely recognition of the MHC-antigen complex and the occupied T cell receptor (5,6), and nonspecific or accessory signals, such as expression of costimulatory molecules or production of IL-1 (7,8).…”

Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis

“…In addition, the expression of influenza viral antigens was also detected in the virally exposed NK cells by immunofluorescent staining. In parallel, purified resting primary human T cells, which cannot be directly infected by influenza virus (24), were included as a negative control. After treatment with influenza virus, no positive staining was found in these cells (Fig.…”

Syncytium Formation and HIV-1 Replication Are Both Accentuated by Purified Influenza and Virus-associated Neuraminidase

“…During the process of infection with flu, it is most likely that the membrane-bound NA removes sialic acid from both cellular and viral glycoconjugates to halt self-agglutination of viruses (30). Human flu virus has the capacity to interact with and infect human macrophages and lymphocytes, two mononuclear cell types known to harbor HIV-1 (31). In patients infected with flu virus, viral replication is occurring on the mucosal surface of respiratory tracts and virions are also found in mucosa-associated lymphoid tissue that is also one of the natural reservoir of HIV-1 (32-34), therefore suggesting the possible co-localization of both pathogens at the same site.…”