Mossman SP, O'Neil SP, Israel ZR, Maul DH, Dandekar S, Mullins JI, Fultz PN, Hoover EA; Symposium on Nonhuman Primate Models for AIDS.
J Med Primatol. 1992 Feb-May; 21: 69 (abstract no. 48).
Department of Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Pigtail and cynomolgus macaques inoculated with SIVsmmPBj14 clone 1.9 undergo an acute infection characterised by profuse diarrhea, lymphadenopathy, fever and skin rash. The acute symptoms appear at about 7 days post infection and are resolved within 14 days, provided intravenous rehydration therapy is administered. The macaques then enter into a chronic phase of infection. We have focused on the mechanism of enteropathy in acute phase PBj14 infected macaques as a model to gain insight into HIV-related enteritis in humans. To determine the distribution of target cells infected by SIV we examined intestinal tissues from a cynomolgus monkey necropsied at the onset of PBj acute disease (5 days post infection) and analysed for SIV RNA by in situ hybridisation. Viral RNA was identified within mononuclear leukocytes in the lamina propria and the lymphoid patches of the ileum and the colon. However, no infected enterocytes were detected. Thus we reasoned that SIVsmmPBj14 induced enteropathy was perhaps more likely to be mediated by infected immune cells in the gut mucosa, possibly through the production of a factor(s) toxic to the absorptive cells. To explore this hypothesis we determined whether PBj14 could infect a number of intestinal epithelial cell lines in vitro, either directly or by cocultivation with infected human PBMC and whether soluble products from macaque and human lymphoid cells were cytotoxic for these cell. SIVsmmPBj14 was unable to infect the human colon carcinoma cell lines HT-29, CaCo-2, SW620 and T84 and the rat small intestinal cell line IEC-18 when monitored by reverse transcriptase assay and by in situ hybridisation. However, supernatants from cultures of activated human and monkey T cells and macrophages have been found to be cytotoxic to HT-29 cells. The identity of the factor(s) responsible for killing HT-29 cells is currently under investigation.
Publication Types:
Keywords:
- Animals
- HIV Infections
- Humans
- In Situ Hybridization
- In Vitro
- Intestinal Diseases
- Intestine, Small
- Intestines
- Macaca
- Macaca fascicularis
- RNA, Viral
- Rats
- Simian immunodeficiency virus
- T-Lymphocytes
Other ID:
UI: 102182924
From Meeting Abstracts