A Simian Immunodeficiency Virus-Infected Macaque Model of Enterocytozoon bieneusi Infection

Abstract

Microsporidiosis caused by Enterocytozoon bieneusi is a common opportunistic infection in patients with HIV/AIDS and those on immunosuppressive therapy. A significant loss of mucosal or peripheral CD4⁺ T cells and subsequent dysfunction of the intestinal immune system may be responsible for the development of chronic microsporidiosis in these patients. We have used the Simian immunodeficiency virus (SIV)-infected macaque model to investigate this relationship. To establish the course of E. bieneusi infection in SIV-infected animals, four SIV-infected animals were experimentally challenged with E. bieneusi when their CD4⁺ counts dropped to less than 300 cells/μL of blood. Analysis of fecal samples by nested polymerase chain reaction revealed that three out of four E. bieneusi-infected macaques continued to shed spores for 7–24 months after infection, an indication of chronic microsporidiosis. Four other SIV-infected macaques, after having an initial negative phase, spontaneously acquired E. bieneusi infection when their CD4⁺ counts dropped to less than 600 cells/μL of blood and shed spores for 8–19 months. The shedding of E. bieneusi spores in the feces increased relative to decrease in peripheral blood CD4⁺ T cell numbers. Gut biopsies were obtained before and after challenge to phenotype the mucosal lymphocyte subsets using flow cytometry. The immunophenotypic analysis showed no restoration of CD4⁺ T cells after E. bieneusi infection in the intestinal cells. A slight increase in the percentage population of CD4⁺ T cells in peripheral blood did not have any effect on the control of E. bieneusi infection in the SIV-infected macaques. These preliminary studies demonstrate that SIV-infected macaques develop chronic E. bieneusi infections as their CD4⁺ counts dropped to below 300 cells/μL of blood.