Social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome

Abstract

From early in the AIDS epidemic, psychosocial stressors have been proposed as contributors to the variation in disease course. To test this hypothesis, rhesus macaques were assigned to stable or unstable social conditions and were inoculated with the simian immunodeficiency virus. Animals in the unstable condition displayed more agonism and less affiliation, shorter survival, and lower basal concentrations of plasma cortisol compared with stable animals. Early after inoculation, but before the emergence of group differences in cortisol levels, animals receiving social threats had higher concentrations of simian immunodeficiency virus RNA in plasma, and those engaging in affiliation had lower concentrations. The results indicate that social factors can have a significant impact on the course of immunodeficiency disease. Socially induced changes in pituitaryadrenal hormones may be one mechanism mediating this relationship.

Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes

“…Social stress is known to suppress innate antiviral responses via neural inhibition of IFN gene transcription (4,(29)(30)(31). Such dynamics comprise a significant part of the APC transcriptional repression observed here (particularly in plasmacytoid dendritic cells, which are the primary IFN-producing leukocytes) (23), providing a cellular context for relationships between social adversity and viral infection (11,28,31,32). As sentinels for damaged tissue and invading pathogens, APCs have also evolved a central role in the activation and guidance of T and B lymphocytes as they mount more complex adaptive immune responses (15,23).…”

Differential detection of B virus and rhesus cytomegalovirus in rhesus macaques FN1

“…Examples of the contribution of social stress to virus pathogenesis have been described for both humans (Glaser et al, 1999;Glaser & Kiecolt-Glaser, 1997;Padgett et al, 1998) and non-human primates (Baroncelli et al, 1997;Capitanio et al, 1998b). In this study stress was created by moving, pair-housing with a new animal and submitting each animal to daily sample taking.…”

Stress-induced remodeling of lymphoid innervation

“…Given previous in vitro evidence that NE can accelerate HIV-1 replication by up-regulating viral co-receptors (Cole, Jamieson et al 1999;Cole, Naliboff et al 2001), inducing viral gene transcription (Cole, Korin et al 1998;Cole, Naliboff et al 2001), and inhibiting antiviral cytokine responses (Cole, Korin et al 1998;Collado-Hidalgo, Sung et al 2006), we sought to determine whether SNS neural fibers might be plausible influences on viral replication within lymphoid tissue. We biopsied axillary and inguinal lymph nodes from adult male rhesus macaques after 39 weeks of daily social stress (unstable social conditions: 100 minutes of caging with 1-3 different conspecifics each weekday) or an equivalent amount of non-stressful social interaction (stable social conditions: 100 minutes of caging with the same 2 conspecifics each day) (as detailed in (Capitanio, Mendoza et al 1998;Sloan, Capitanio et al 2007b)). Molecular histology supported the hypothesis that SNS activity enhances viral replication by showing a substantial increase in the transcription of SIV RNA in cells within 250 μm of a catecholaminergic varicosity ).…”