Activation of an HIV-LTR-CAT Transgene in Murine Macrophages by Interferon-γ in Synergism with other Cytokines or Endotoxin

Abstract

The initial infection with human immunodeficiency virus (HIV) and early viremia are usually caused by macrophage (MΦ)-tropic and non-syncytium- inducing HIV variants, while syncytium-inducing T cell infecting HIV arise later in the disease (1). Therefore, factors that influence the propagation of HIV within MΦs may be critical in determining the progression of AIDS. Among the cytokines frequently elevated in HIV⁺ patients and capable of influencing MΦ functions are IFN-γ, IL-6, TNF-α and TGF-ß (2–5). Secondary infections with gram negative organisms common in HIV patients are probably sources of LPS. The purpose of the present investigation was to identify modulatory factors that suppress and/or activate the HIV genome within MΦs in a noninfectious animal model and to study their mechanism of action. Transgenic FVB/N mice homozygous for the LTR sequence (-453/+80) which contains the transcriptional regulatory elements of HIV linked to the bacterial gene encoding CAT as the reporter gene were used as an experimental model (6). Thus, alterations in HIV-LTR directed expression of CAT would be analogous to changes in viral expression in cells harboring integrated virus. Results from studies on the influence of biological response modifiers (BRMs) and UV-irradiation on HIV-LTRCAT expression in MΦs and/or epidermis indicate the usefulness of this animal model (6–9), particularly when compared with those obtained with HIV-LTR (with or without Tat) transfected human MΦs (10).