Rapid mucosal CD4+ T-cell depletion and enteropathy in simian immunodeficiency virus–infected rhesus macaques

Kewenig, S.; Schneider, Thomas; Hohloch, Karin; Lampe–Dreyer‡, Kathrin; Ullrich, Reiner; Stolte, Nicole; Stahl–Hennig∥, Christiane; Kaup, F.‐J.; Stallmach, Andreas; Zeitz, Martin

doi:10.1016/s0016-5085(99)70014-4

Cited by 134 publications

(118 citation statements)

References 29 publications

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“…Recent studies suggest that analysis of lymph nodes and mucosa-associated lymphocytes is a more sensitive approach to detecting alterations in lymphocyte subpopulations due to HIV or simian immunodeficiency virus infection (37,47,69,73,75). This was apparent in the present study, as no lymphocyte subset alterations were seen in the peripheral blood of any FIV-challenged animals.…”

Section: Discussionsupporting

confidence: 55%

Oral Immunization with RecombinantListeria monocytogenesControls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

Stevens¹,

Howard

Nordone³

et al. 2004

J Virol

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Section: Discussionsupporting

confidence: 55%

Oral Immunization with RecombinantListeria monocytogenesControls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

Stevens¹,

Howard

Nordone³

et al. 2004

J Virol

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“…Such severe CD4 ϩ T-cell impairment has been shown to preferentially involve gut-residing memory-activated CD4 ϩ CCR5 ϩ T cells, reflecting the well-known prevalence of CCR5-tropic viruses in the early phases of infection. Almost concomitantly, Veazey et al and Kewenig et al showed that more than 70% of intestinal CD4 ϩ cells were depleted as early as 21 days post-SIVmac239 infection (72,73), and several subsequent studies then confirmed these findings and shed further light onto the mechanistic pathways underlying CD4 ϩ T-cell depletion (34,(74)(75)(76). Among those studies, Mattapallil et al were able to demonstrate the presence of SIV DNA in up to 60% of intestinal CD4 ϩ T cells as early as 10 days after experimental SIVmac251 infection, therefore emphasizing the role of direct virus-mediated killing of CD4 ϩ T cells as a mechanism causing the observed depletion (70).…”

Section: Pathogenesis Of Hiv/siv-associated Microbial Translocationmentioning

confidence: 98%

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

2013

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SUMMARYIn pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections, the translocation of microbial products from the gastrointestinal (GI) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. Consistently, microbial translocation is not present in nonpathogenic SIV infections of natural host species.In vivostudies demonstrated that HIV/SIV-associated microbial translocation results from a series of immunopathological events occurring at the GI mucosa: (i) early and severe mucosal CD4+depletion, (ii) mucosal immune hyperactivation/persistent inflammation; (iii) damage to the integrity of the intestinal epithelium with enterocyte apoptosis and tight junction disruption; and (iv) subverted the gut microbiome, with a predominance of opportunistic bacteria. Directin situevidence of microbial translocation has been provided for SIV-infected rhesus macaques showing translocated microbial products in the intestinal lamina propria and distant sites. While the mechanisms by which microbial translocation causes immune activation remain controversial, a key pathogenic event appears to be innate immunity activation via Toll-like receptors and other pathogen recognition receptors. Accumulating clinical observations suggest that microbial translocation might affect HIV disease progression, response to therapy, and non-AIDS comorbidities. Given its detrimental effect on overall immunity, several interventions to prevent/block microbial translocation are currently under investigation as novel therapeutic agents for HIV/AIDS.

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“…Indeed, within days of infection, a similarly dramatic depletion of GI CD4 T cells was observed in these animals. 33 Furthermore, SIV-infected macaques also manifest enteropathy, 34 which is associated with decreased expression of genes such as trefoils that are involved in mucosal repair. 35 Hence, in pathogenic SIV infection of rhesus macaques, the majority of the body's CD4 T cells are depleted within the short acute phase of the infection -a finding not reflected by analysis of peripheral blood or lymph nodes.…”

Section: Gastrointestinal Cd4 T-cell Depletionmentioning

confidence: 99%

HIV infection and the gastrointestinal immune system

2008

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There has recently been a resurgence of interest in the gastrointestinal pathology observed in patients infected with HIV. The gastrointestinal tract is a major site of HIV replication, which results in massive depletion of lamina propria CD4 T cells during acute infection. Highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of gastrointestinal CD4 T cells. The gastrointestinal pathology associated with HIV infection comprises significant enteropathy with increased levels of inflammation and decreased levels of mucosal repair and regeneration. Assessment of gut mucosal immune system has provided novel directions for therapeutic interventions that modify the consequences of acute HIV infection.The mucosal surface of the gastrointestinal (GI) tract forms a unique anatomical and physiological niche, serving as a predominant structural and immunological barrier against the microorganisms of the outside world. In addition, the tightly apposed enterocytes that form the single cell layer of the mucosal epithelium also absorb water and nutrients during the digestive process, which is critical to host survival. Hence, loss of the integrity of the mucosal surface results in multiple deleterious sequelae.

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Rapid mucosal CD4+ T-cell depletion and enteropathy in simian immunodeficiency virus–infected rhesus macaques

Cited by 134 publications

References 29 publications

Oral Immunization with RecombinantListeria monocytogenesControls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

Oral Immunization with RecombinantListeria monocytogenesControls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

HIV infection and the gastrointestinal immune system

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