The influence of cold or isolation stress on neuroinvasiveness and virulence of an attenuated variant of West Nile virus

Abstract

The effect of cold or isolation stress on neuroinvasiveness and virulence was investigated in mice inoculated with an attenuated WNV (WN-25) strain. The WN-25 variant differed from the parent strain by its inability to kill mice after I.P. injection though it was able to immunize even after injection with low doses of virus. Exposure of inoculated mice for 5 minutes a day to cold water (1 +/- 0.5 degrees C) for 8 days resulted in 60% mortality, while in nonstressed infected mice no death was observed. Cold or isolation stress increased the virus level in the brain to 8.9 and 7.4 log 10 PFU as compared to no virus in the infected control. Moreover, it was found that virus level in the spleen of stressed mice reached 3.4 and 3.7 log 10 PFU respectively, while in non-stressed mice no virus was detected. The virus which was isolated from the brain of moribund stressed mice was extremely virulent: I.P. inoculation of as little as 10 PFU caused death to normal non-stressed mice. We suggest that cold or isolation stress conditions in mice inoculated with an attenuated strain induce a selection process. The virus which was isolated from the brain of stressed mice changes its virulence and kills like wild type WNV.

Social regulation of leukocyte homeostasis: The role of glucocorticoid sensitivity

“…The implications of such effects for immunologic effector functions or disease pathophysiology remain unclear because SEBAS lacks direct measures of those processes. However, the pattern of decreasing leukocyte functional sensitivity to HPA regulation with increasing levels of subjective social isolation is consistent with the profile of increased inflammatory disease risk observed in human epidemiologic studies (Berkman 1977;House, Landis et al 1988;Reynolds and Kaplan 1990;Krongrad, Lai et al 1996;Seeman 1996;Cohen, Doyle et al 1997;Berkman and Kawachi 2000;Cacioppo and Hawkley 2003;Cole, Kemeny et al 2003;Soler-Villa, Kasl et al 2003;Caspi, Harrington et al 2006;Kroenke, Kubzansky et al 2006) and in animal models (Sklar and Anisman 1980;Ben-Nathan, Lustig et al 1989;Shively, Clarkson et al 1989;Clausing, Bocker et al 1994;Hilakivi-Clarke and Dickson 1995;Villano Bonamin, Barbuto et al 2001;Wu, Murata et al 2001;McClintock, Conzen et al 2005;Hermes, Rosenthal et al 2006;Thaker, Han et al 2006). A significant challenge for future research lies in understanding the teleologic basis for these relationships.…”

Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice

“…While these results provide mechanistic insights into PS-related alterations in antimicrobial defense, they also provide a likely pathomechanism for the increased risk of cutaneous (and extracutaneous) infections during PS (13,15,18,20,24) as well as both systemic and topical GC therapy (47,48,57,58). It should be noted, however, that PS or GC therapy could increase the risk of cutaneous infections by other, unrelated mechanisms; for example, GCs decrease epidermal dendritic cell function (59,60), another important participant in cutaneous innate immunity, and also decrease epidermal primary cytokine levels (33), which could influence antimicrobial defense by a variety of downstream mechanisms.…”

“…Although recent studies in both humans and experimental animals suggest that PS compromises host defenses against bacterial and viral infections (13)(14)(15)(16)(17)(18)(19)(20)(21), the pathogenic mechanisms remain unknown. Three potentially interconnected mechanisms have been proposed to explain the negative impact of PS on host defenses against infection and neoplasia: (a) psychoneuroimmunoendocrine dysfunction, which leads to increased proinflammatory neuropeptide and cytokine production in a manner either dependent or independent of the hypothalamic-pituitary-adrenal (HPA) axis (18)(19)(20)(21)(22)(23)(24); (b) increased plasma levels of endogenous glucocorticoid (GC) caused by activation of the HPA axis (16, 18-21, 24, 25); and (c) a cutaneous steroidogenic system, with localized production of corticotropin-releasing factor (CRF) (26,27), which could mediate the adverse effects of PS on skin.…”

Inhalation anesthetic‐induced neuroinvasion by an attenuated strain of West Nile virus in mice

“…To this end, an attenuated strain of West Nile virus was employed, designated WN-25, that is uniquely de®-cient in its ability to penetrate the brain as compared with its wild-type progenitor [Ben-Nathan et al, 1989]. The naturally occurring West Nile virus is a neurotropic RNA arbovirus, a member of the¯avivirus genus of the family Flaviviridae.…”