Arch Virol (t988) 99:9-19 Archives vi rology © by Springer-Verlag t 988 Acid-labile human interferon alpha production by peripheral blood mononuclear cells stimulated by HIV-infected cells M. R. Capobianchi, F. De Marco, P. Di Marco, and F. Dianzani The Institute of Virology, University of Rome, Rome, Italy Accepted December 18, 1987 Summary. We compared the properties of interferon (IFN) induced in peripheral blood mononuclear cells (PBMC) by free infectious HIV to that induced by HIV-infected cells fixed with glutaraldehyde. While the IFN induced by HIV was a conventional IFN alpha, the IFN induced by HIV-infected cells, although sharing with IFN alpha both antigenic properties and molecular weight, was strongly inactivated by treatment at pH lower than 4. The ability to induce acid-labile IFN alpha was exerted both by the chronically--infected cell line H9/HIV and by normal PBMC infected in vitro with HIV, while infection of inducers cells with viruses other than HIV made these cells capable of inducing only acid-stable IFN alpha. The cell involved in the production of this type of IFN seems to be B-lymphocyte. Because the presence of acid-labile IFN alpha in the serum of AIDS patients has been described, we suggest that this unusual IFN derives from interaction between circulating B-lymphocytes and the HIV-infected cells. Introduction Acquired immunodeficiency syndrome (AIDS) is caused by infection with T- cell tropic retroviruses known as HTLVIII-LAV, recently reclassified HIV [24]. These viruses are capable of selectively infecting CD4 + lymphocytes, but rep- lication in other cell types has been reported, provided the target cells are expressing CD4 antigen [10]. The disease is characterized by a profound defect in cell-mediated immunity, as shown by decreased hypersensitivity skin reac- tions, decreased response in vitro to antigenic and/or mitogenic stimulation, decreased cytotoxic lymphocyte responses, polyclonal B-cell activation, de- creased monocyte chemotaxis and a number of serologic abnormalities [15]. Among the serologic abnormalities, the presence of an unusual acid-labile in- terferon (IFN) has been repeatedly found, and it is considered to be a marker of infection with HIV evolving toward illness, as more than 80% of sera from patients with full-blown AIDS or with AIDS-related complex (ARC) have been found to display in their sera acid-labile IFN alpha [1, 6, 12, 19].