HIV/SIV Enteropathy

Abstract

Evidence is increasing that HIV/SIV-induced changes in the highly differentiated gut-associated immune system play a central role in the pathogenesis of gastrointestinal manifestations in HIV/SIV infection. It has been shown in both humans infected with HIV and in nonhuman primates infected with SIV that a rapid, very early, and more pronounced loss of CD4+ T-cells occurs in the mucosa in comparison to the peripheral blood. The loss of this important regulatory T-cell subset might explain mucosal immunodeficiency with the consequence of opportunistic mucosal infections. In addition, there is evidence that small intestinal damage occurs independently of secondary infections (HIV/SIV enteropathy). In late-stage human disease, HIV enteropathy is characterized by villous atrophy with hyporegeneration and dysmaturation of intestinal epithelial cells. In SIV infection of macaques, villous atrophy is a very early event; however, it is accompanied by crypt cell hyperproliferation. Early- and late-stage enteropathy in immunodeficiency virus infection may represent two types of immunologically mediated mucosal transformation in which the number and state of activation of regulatory T cells determine whether hypo- or hyperproliferative villous atrophy occurs.

Unique Pathology in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques Is Consistent with a Pathogenesis Distinct from That of Classical AIDS

“…Pathological findings in these macaques included severe enteritis, characterized by villus blunting, and fusion, as shown in a representative section of ileum in Fig. 1A, similar to the SIV enteropathy previously described in SIV infection (30,75,78) and are in keeping with the major impact of SIV on the GI tract (75). Opportunistic infections (OIs) were not observed in either the GI tract or other organs, suggesting that clinical disease in these animals was the direct result of SIV infection rather than secondary to immune suppression.…”

“…Thus, it is not certain whether RP macaques inoculated with other SIV strains would segregate so clearly from slower progressors, as observed for SIVsmE543 and SIVsmE660 in the present study. The pathological features that we associated with rapid progression, such as MNGC formation (4), macrophage tropism (2, 17, 55), SIV enteropathy (30,43,78), and SIVE (3,61,77,81), are not unique to one specific strain of SIV. For example, previous studies of SIVmac239 and SIVsm strains have demonstrated that SIVE is highly associated with lack of SIV-specific antibody responses and a rapid disease course (3,61,77).…”

Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques

“…5 HIV/SIVassociated pathology in the GI tract includes epithelial hyperplasiainduced villous atrophy, abnormal cellular infiltrates, disrupted lymphoid architecture, and increased apoptotic cells, mostly attributed to an overt and chronic inflammatory immune response during HIV/SIV infection. [6][7][8] By contrast, SIV-infected natural nonhuman primate hosts such as sooty mangabeys (SMs) and African green monkeys do not progress to simian AIDS, unlike nonnatural hosts such as infected rhesus macaques (RMs, Macaca mulatta). 9,10 Prolonged immune activation is thought to contribute to disease progression in nonnatural hosts because natural hosts quickly dampen generalized immune activation after the acute phase of SIV infection.…”

Simian immunodeficiency virus (SIV)–specific cytotoxic T lymphocytes in gastrointestinal tissues of chronically SIV-infected rhesus monkeys

“…These patients often manifest clinical GI abnormalities, including nutrient malabsorption, malnutrition, diarrhea, and weight loss. 1,2 Pathologic changes in GI tissues from HIV-infected individuals include inflammatory infiltrates, villus blunting, and crypt hyperplasia. 3 A progressive loss of the CD4 ϩ T lymphocytes in the GI tract is observed early following infection.…”