Antiviral Therapy during Primary Simian Immunodeficiency Virus Infection Fails To Prevent Acute Loss of CD4
            <sup>+</sup>
            T Cells in Gut Mucosa but Enhances Their Rapid Restoration through Central Memory T Cells

Verhoeven, David; Sankaran, Sumathi; Silvey, Melanie; Dandekar, Satya

doi:10.1128/jvi.02164-07

Cited by 59 publications

(87 citation statements)

References 75 publications

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“…in untreated animals. In line with our findings, Verhoeven et al (31), using a similar ART regimen (30 mg/kg of body weight) that was initiated at day 7 p.i., reported a significant decline in plasma viral loads at 2 weeks p.i. in treated animals compared to those in untreated animals.…”

supporting

confidence: 79%

Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection

Kader

Hassan

Eberly

et al. 2008

J Virol

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The rectal mucosa is a major site for human immunodeficiency virus entry and CD4 T-cell depletion. The early and near-total loss of these cells from the rectal mucosa severely compromises the ability of the mucosal immune system to control various opportunistic infections. Protecting these cells from infection and destruction can delay disease progression, leading to a better long-term outcome. Here we show that effective suppression of viral infection in memory CD4 T cells from the rectal mucosa and peripheral blood to a very low level with antiretroviral therapy (ART) initiated prior to the peak of infection is associated with opposite outcomes in these tissues. A near-total loss of CD4 T cells in the rectal mucosa contrasted with preservation of most memory CD4 T cells in peripheral blood during the course of treatment. Interestingly, ART significantly reduced viral infection in memory CD4 T cells from both rectal mucosa and peripheral blood. Although early ART was of limited value in protecting the CD4 T cells in the rectal mucosa, the significant preservation of peripheral CD4 T cells could contribute to maintaining immune competence, leading to a better long-term outcome.

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supporting

confidence: 79%

Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection

Kader

Hassan

Eberly

et al. 2008

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: 57%

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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“…During chronic HIV infection, several studies have shown that maintenance of EM numbers is dependent on the preservation of CM cells for their homeostasis and that this CM-dependent EM production progressively declines during chronic infection (25,33). The frequency of CD4 CM cells in GALT was found to be associated with better mucosal CD4 T cell restoration (9,44,48). Despite replenishing of the EM pool by CM cells, the frequency of CD4 cells remains low at the mucosal sites during chronic HIV infection compared to uninfected individuals (9,44).…”

mentioning

confidence: 99%

CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

Gumbi

Jaumdally

Salkinder

et al. 2011

J Virol

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In blood, the accumulation of terminally differentiated (TD) T cells during HIV infection is associated with CD4 T cell loss and HIV disease progression. Here, we investigated the maintenance and functional characteristics of memory T cells at the cervix. We found that CD4 T cell depletion at the cervix mirrors CD4 depletion in blood. In all women, depletion of CD4 T cells at the cervix was associated with significant reductions in

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Antiviral Therapy during Primary Simian Immunodeficiency Virus Infection Fails To Prevent Acute Loss of CD4 ⁺ T Cells in Gut Mucosa but Enhances Their Rapid Restoration through Central Memory T Cells

Abstract: Gut-associated lymphoid tissue (GALT) is an early target of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV

Cited by 59 publications

References 75 publications

Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection

Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

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Antiviral Therapy during Primary Simian Immunodeficiency Virus Infection Fails To Prevent Acute Loss of CD4 + T Cells in Gut Mucosa but Enhances Their Rapid Restoration through Central Memory T Cells

Abstract: Gut-associated lymphoid tissue (GALT) is an early target of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV

Cited by 59 publications

References 75 publications

Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection

Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

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Product

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Antiviral Therapy during Primary Simian Immunodeficiency Virus Infection Fails To Prevent Acute Loss of CD4 ⁺ T Cells in Gut Mucosa but Enhances Their Rapid Restoration through Central Memory T Cells