Identification of Friend murine retrovirus‐infected immune cells and studies of the effects of sex and steroid hormones in the early phase of infection

Abstract

Male mice are more susceptible than female mice to the murine retrovirus FIS-2. We previously reported that sex-related factors influence early virus replication via mechanisms involving a glucocorticoid response element (GRE) in the long terminal repeat (LTR) enhancer region. In the present study, we investigated further the influence of sex and steroid hormones on early murine retrovirus dissemination and immune functions. In male mice we found a correlation between an early expansion of the CD8+ cell subset and rapid infection of lymphocytes, including CD8+ cells. Virus load in blood declined faster in females than in males, and the postpeak declines coincided with more rapidly generation of antibodies against virus-positive cells. Moreover, female-derived T-cells responded better to in vitro mitogen stimuli than male-derived T-cells. Physiological concentrations of progesterone and dexamethasone induced a dose-dependent inhibition of T-cell proliferation. Administration of progestin in vivo did not modify early FIS-2 production in female mice. Male castrated mice, who were notably less involved in aggressive behaviour and fighting compared to male control mice, had a significant delay of virus dissemination. We suggest that testosterone-dependent aggression, with successive enhanced stress hormone levels, may influence both FIS-2 replication and immune responses during infection.

Control of Pathogenicity and Disease Specificity of a T-Lymphomagenic Gammaretrovirus by E-Box Motifs but Not by an Overlapping Glucocorticoid Response Element

“…Both sites appear to be conserved in proviruses isolated from T lymphomas, suggesting that both are needed for viral T lymphomagenesis (5,47,53). Previously, a correlation was made between the presence of a GRE in FIS2 and a significant sex difference in the susceptibility to this virus (6)(7)(8).…”

The Glucocorticoid Receptor in Retroviral Infection

“…Vpr also potentiated the glucocorticoid-induced inhibition of other immunologically important cytokines such as IL-2, IL-10, TNF alpha and IL-4, all of which are NFκB -dependent (Fakruddin & Laurence, 2005). Both the GR and Vpr are involved in the apoptosis in T cells and dendritic cells (Hapgood & Tomasicchio, 2010;Bruland et al, 2003b). In addition, patients with AIDS and normal cortisol secretion have manifestations compatible with glucocorticoid hypersensitivity of the immune system, such as suppression of innate and cellular immunity.…”