The Effects of Dietary T-2 Toxin on Acute Herpes Simplex Virus Type 1 Infection in Mice

Abstract

Abstract. Young male white Swiss mice were fed control diet or diet supplemented with 20 or 10 parts per million (ppm) of T-2 toxin for two or three weeks. These mice then were inoculated with herpes simplex virus type I (HSV-1) (9.6 X lo6 plaque forming units) intraperitoneally. To compare the effects of T-2 toxin against a known immunosuppressive drug, cyclophosphamide was injected intraperitoneally at I50 mg/kg, 24 hours after treatment with HSV-1. into mice fed the control diet. Mice were necropsied and tissues were collected for microscopic and virologic examination.White Swiss mice which consumed a daily diet containing 20 ppm of T-2 toxin for two or three weeks were highly susceptible to HSV-I infection and 27 of 36 (75%) died as a result of extensive hepatic and adrenal necrosis. Although HSV-1 was isolated from livers and brains of mice fed 20 ppm of T-2 toxin for two or three weeks, there was little or no inflammatory response found in the adrenals, livers, spinal cords, brains, or ganglia. The necrotizing encephalomyelitis observed in control mice was absent.High levels of dietary T-2 toxin appeared to be more immunosuppressive than cyclophosphamide because only one mouse died after treatment with HSV-1 and cyclophosphamide. Mice treated with cyclophosphamide had changes in brain, spinal cord, spleens, thymus, and bone marrow which were similar to those fed 20 ppm of T-2 toxin and infected with HSV-I, however, liver lesions were much less severe.HSV-I-infected mice on a diet with 10 ppm T-2 toxin had lesions of intermediate severity when compared with HSV-I-infected mice fed a diet with 20 ppm T-2 toxin and HSV-Iinfected mice on control diets. Necrosis was less extensive in the livers and adrenals. The infrequent isolation of virus from liver and brain was consistent with the lack of intranuclear inclusion bodies and a more marked inflammatory response. Ten ppm of dietary T-2 toxin only depressed bone marrow and splenic red pulp to a mild or moderate degree. This may have enhanced the necrotizing encephalomyelitis observed in mice killed on days 6 and 8 after HSV-1 infection.Liver lesions were mild and those of the adrenals were moderate in mice fed control diet. The rare isolation of HSV-I from the liver and brain and the finding of a moderate to severe necrotizing encephalomyelitis in these mice was consistent with an essentially functional immune system. T-2 toxin, a trichothecene mycotoxin produced by Fzisurizim spp fungi [5 1, 737

T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-γ responses

“…and oral exposure to the toxin induces apoptosis of hematopoietic and lymphoid tissues, including bone marrow, Peyer's patches, spleen, and thymus (Ihara et al, 1997;Shinozuka et al, 1997aShinozuka et al, , 1997bIslam et al, 1998;Nagata et al, 2001). Experimental animals similarly treated with T-2 are Toxicology and Applied Pharmacology 214 (2006) 318 -325 www.elsevier.com/locate/ytaap more susceptible to systemic infections by Salmonella Typhimurium (Tai and Pestka, 1990;Ziprin and Elissalde, 1990;Kubena et al, 2001), Listeria monocytogenes (Ziprin and McMurray, 1988;Ziprin et al, 1987), Babesia microti (Corrier and Wagner, 1988), Mycobacterium (Kanai and Kondo, 1984;Ziprin and McMurray, 1988), and Herpes simplex virus (Friend et al, 1983). Although the intestine is a principal target in ATA, little is known of T-2′s capacity to suppress the gut mucosal immune response.…”

Effects of T-2 Toxin on Turkey Herpesvirus–Induced Vaccinal Immunity Against Marek's Disease

“…In addition, T-2 toxin has been reported to induce apoptosis in thymus, hematopoietic tissues and HL-60 human promyelocytic leukemia cells (26,56,73). Repeated exposure to T-2 toxin also causes immunosuppression and decreases the resistance of exposed animals to various infectious diseases such as Newcastle disease (29), salmonellosis, and Cryptosporidiosis in chickens (3,4,5) and mice (60, 61,76), and tuberculosis (76), listeriosis (13), Toxoplasma gondii, and herpes simplex infection in mice (17,63). In addition, T-2 toxin may impair host control of tumor cell growth (11,52,53).…”