Journal ArticleDOI
Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs
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TLDR
A critical role of co-receptor utilization in viral pathogenesis is suggested and in vivo infection with chimeric simian-human immunodeficiency virus provides a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV- 1 envelope protein.Abstract:
Infection of macaques with chimeric simian-human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)-specific enveloped virus, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIVSF162P caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells, whereas infection with SHIVSF33A.2 caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.read more
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Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.
Saurabh Mehandru,Michael A. Poles,Michael A. Poles,Klara Tenner-Racz,Amir Horowitz,Amir Horowitz,Arlene Hurley,Christine Hogan,Daniel Boden,Paul Racz,Martin Markowitz +10 more
TL;DR: It is demonstrated that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4+ T cell population, a significantly greater CD4- T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy.
Journal ArticleDOI
Fc receptor but not complement binding is important in antibody protection against HIV
Ann J. Hessell,Lars Hangartner,Meredith Hunter,Carin E. G. Havenith,Frank J. Beurskens,Joost M. Bakker,Caroline Lanigan,Gary Landucci,Donald N. Forthal,Paul W. H. I. Parren,Preston A. Marx,Dennis R. Burton +11 more
TL;DR: There is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody.
Journal ArticleDOI
Antibody Protects Macaques against Vaginal Challenge with a Pathogenic R5 Simian/Human Immunodeficiency Virus at Serum Levels Giving Complete Neutralization In Vitro
Paul W. H. I. Parren,Preston A. Marx,Preston A. Marx,Ann J. Hessell,Amara Luckay,Janet M. Harouse,Cecilia Cheng-Mayer,John P. Moore,Dennis R. Burton +8 more
TL;DR: It is shown that passive intravenous transfer of the human neutralizing monoclonal antibody b12 provides dose-dependent protection to macaques vaginally challenged with the R5 virus SHIV162P4, suggesting that a vaccine based on antibody alone would need to sustain serum neutralizing antibody titers of the order of 1:400 to achieve sterile protection but that lower titers, around 1:100, could provide a significant benefit.
Journal ArticleDOI
HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells.
James Arthos,Claudia Cicala,Elena Martinelli,Elena Martinelli,Katilyn Macleod,Donald Van Ryk,Danlan Wei,Zhen Xiao,Timothy D. Veenstra,Thomas P Conrad,Richard A. Lempicki,Sherry McLaughlin,Massimiliano Pascuccio,Ravindra Gopaul,Jonathan P. McNally,Catherine C. Cruz,Nina Censoplano,Eva Chung,Kristin N. Reitano,Shyam Kottilil,Diana J. Goode,Anthony S. Fauci +21 more
TL;DR: It is demonstrated here that the HIV-1 envelope protein gp120 bound to an activated form of α4β7, a peptide motif that mimics structures presented by the natural ligands of α 4β7 in the V2 loop of gp120.
Journal ArticleDOI
T Cell Dynamics in HIV-1 Infection*
TL;DR: A model of HIV-1 pathogenesis is presented in which the protracted loss of CD4(+) T cells results from early viral destruction of selected memory Tcell populations, followed by a combination of profound increases in overall memory T cell turnover, damage to the thymus and other lymphoid tissues, and physiological limitations in peripheral CD4 (+) T cell renewal.
References
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Journal ArticleDOI
HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor
TL;DR: A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy that is a putative G protein-coupled receptor with seven transmembrane segments.
Journal Article
HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein–Coupled Receptor
TL;DR: Fusin this article is a putative G protein-coupled receptor with seven transmembrane segments, which enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and infection.
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HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure.
Jerome A. Zack,Salvatore J. Arrigo,Stacy R. Weitsman,Alan S. Go,Allyson M. Haislip,Irvin S. Y. Chen +5 more
TL;DR: A modification of the polymerase chain reaction method is used to demonstrate that HIV-1 DNA synthesis is initiated in infected quiescent T cells at levels comparable with those of activated T cells.
Journal ArticleDOI
Gastrointestinal Tract as a Major Site of CD4+ T Cell Depletion and Viral Replication in SIV Infection
Ronald S. Veazey,Mary Ann DeMaria,Laura V. Chalifoux,Daniel E. Shvetz,Douglas R. Pauley,Heather Knight,Michael Rosenzweig,R. Paul Johnson,Ronald C. Desrosiers,Andrew A. Lackner +9 more
TL;DR: The intestine appears to be a major target for SIV replication and the major site of CD4+ T cell loss in early SIV infection.
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The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes
TL;DR: The largely reciprocal expression of CXCR4 and CCR5 among peripheral blood T cells implies distinct susceptibility of T cell subsets to viral entry by T cell line- Tropic versus macrophage-tropic strains during the course of HIV infection.