Mechanisms of Gastrointestinal CD4+ T-Cell Depletion during Acute and Early Human Immunodeficiency Virus Type 1 Infection
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| Published in | Journal of Virology Vol. 81; no. 2; pp. 599 - 612 |
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| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.01.2007
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| ISSN | 0022-538X 1098-5514 |
| DOI | 10.1128/JVI.01739-06 |
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| AbstractList | During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+ T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4+ T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4+ T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4+ T cells during AEI. HIV-1 RNA was detected in both "activated" and "nonactivated" mucosal CD4+ T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4+ T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4+ T cells. Subsequently, ongoing infection of susceptible CD4+ T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion.During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+ T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4+ T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4+ T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4+ T cells during AEI. HIV-1 RNA was detected in both "activated" and "nonactivated" mucosal CD4+ T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4+ T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4+ T cells. Subsequently, ongoing infection of susceptible CD4+ T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion. During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4 + T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4 + T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4 + T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4 + T cells during AEI. HIV-1 RNA was detected in both “activated” and “nonactivated” mucosal CD4 + T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4 + T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4 + T cells. Subsequently, ongoing infection of susceptible CD4 + T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+ T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4+ T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4+ T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4+ T cells during AEI. HIV-1 RNA was detected in both "activated" and "nonactivated" mucosal CD4+ T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4+ T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4+ T cells. Subsequently, ongoing infection of susceptible CD4+ T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion. |
| Author | Anita Shet Peter Lopez Michael A. Poles Andrea Low Victoria Manuelli Patrick Jean-Pierre Saurabh Mehandru Martin Markowitz Hiroshi Mohri Paul Racz Klara Tenner-Racz Daniel Boden |
| AuthorAffiliation | Aaron Diamond AIDS Research Center and Rockefeller University, New York, New York 10016, 1 New York University School of Medicine, Department of Medicine, Division of Gastroenterology, New York, New York 10016, 2 Bernhard-Nocht Institut für Tropenmedizin, 20359 Hamburg, Germany 3 |
| AuthorAffiliation_xml | – name: Aaron Diamond AIDS Research Center and Rockefeller University, New York, New York 10016, 1 New York University School of Medicine, Department of Medicine, Division of Gastroenterology, New York, New York 10016, 2 Bernhard-Nocht Institut für Tropenmedizin, 20359 Hamburg, Germany 3 |
| Author_xml | – sequence: 1 givenname: Saurabh surname: Mehandru fullname: Mehandru, Saurabh organization: Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Ave., 7th Fl., New York, NY 10016, USA – sequence: 2 givenname: Michael A surname: Poles fullname: Poles, Michael A – sequence: 3 givenname: Klara surname: Tenner-Racz fullname: Tenner-Racz, Klara – sequence: 4 givenname: Victoria surname: Manuelli fullname: Manuelli, Victoria – sequence: 5 givenname: Patrick surname: Jean-Pierre fullname: Jean-Pierre, Patrick – sequence: 6 givenname: Peter surname: Lopez fullname: Lopez, Peter – sequence: 7 givenname: Anita surname: Shet fullname: Shet, Anita – sequence: 8 givenname: Andrea surname: Low fullname: Low, Andrea – sequence: 9 givenname: Hiroshi surname: Mohri fullname: Mohri, Hiroshi – sequence: 10 givenname: Daniel surname: Boden fullname: Boden, Daniel – sequence: 11 givenname: Paul surname: Racz fullname: Racz, Paul – sequence: 12 givenname: Martin surname: Markowitz fullname: Markowitz, Martin |
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| Keywords | Immunopathology HIV-1 virus Acute Retroviridae AIDS Immune deficiency Lentivirus Mechanism Virology Infection Virus Viral disease T-Lymphocyte Human immunodeficiency virus |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., 7th Fl., New York, NY 10016. Phone: (212) 448-5020. Fax: (212) 725-1126. E-mail: mmarkowitz@adarc.org. |
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Mendeley... During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+ T cells are preferentially depleted from the... During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4 + T cells are preferentially depleted from the... |
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| SubjectTerms | Acute Disease Biological and medical sciences CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - virology Cytotoxicity, Immunologic DNA, Viral - blood Female Flow Cytometry Fundamental and applied biological sciences. Psychology Gastrointestinal Tract - immunology Gastrointestinal Tract - virology HIV Infections - immunology HIV Infections - virology HIV-1 - isolation & purification HIV-1 - pathogenicity Human viral diseases Humans Immunohistochemistry Immunologic Memory Infectious diseases Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - virology Lymphocyte Activation Male Medical sciences Microbiology Miscellaneous RNA, Viral - blood Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load Virology Virus-Cell Interactions |
| Title | Mechanisms of Gastrointestinal CD4+ T-Cell Depletion during Acute and Early Human Immunodeficiency Virus Type 1 Infection |
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