Infection of human tonsil histocultures: A model for HIV pathogenesis

Glushakova, Svetlana; Baibakov, Boris; Margolis, Leonid; Zimmerberg, Joshua

doi:10.1038/nm1295-1320

Cited by 174 publications

(242 citation statements)

References 9 publications

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“…Cell viability in the organ culture systems was confirmed by finding that many of the tissue pieces acquired a surface coating of epithelial cells after 5-7 days in culture. As expected from previously published studies (Glushakova et al 1995), when cut pieces of tonsil were infected with cell-free HIV, there was a time-and virus-dosedependent increase in the number of HIV-infected cells (primarily CD4 ϩ T cells), as judged by accumulation of intracellular HIV p24 antigen. At day 1 postinfection with a primary patient isolate of HIV, HIV96-480, p24 signal was not detectable ( Figure 2A), but by days 4 and 6, there were numerous clusters of cells that were strongly positive for intracellular p24 ( Figures 2B and 2C).…”

Section: Resultssupporting

confidence: 85%

Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

Maher

Zhang

Schacker

et al. 2005

J Histochem Cytochem.

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The majority of newly acquired HIV infections are believed to occur following transmission of virus infectivity across mucosal surfaces, although many mechanistic details still remain unresolved. We have used human ex vivo organ cultures and primary cell populations to analyze the cellular and molecular basis for mucosal HIV transmission. By using human palatine tonsil from routine tonsillectomies and semen from HIV-positive donors, we have created an experimental equivalent to oral HIV transmission. HIV infection was readily transferred into tonsillar lymphocytes, but this transmission into lymphocytes was dramatically reduced when the exposed lymphocyte populations were protected by intact mucosal surfaces. In this study, we consider the impact that leukocyte activation and morphological aberrations in surface structure may have on susceptibility to primary HIV infection and introduce novel time-lapse confocal microscopy procedures that begin to reveal the dynamic complexity associated with cell-mediated HIV transmission. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

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Section: Resultssupporting

confidence: 85%

Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

Maher

Zhang

Schacker

et al. 2005

J Histochem Cytochem.

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“…The tonsils were washed thoroughly with medium containing antibiotics and then sectioned into small pieces of 6 -9 mm 3 . These tissue blocks were placed on top of collagen sponge gels in the culture medium at the air-liquid interface as we previously described (27,30).…”

Section: Cell Lines and Tonsillar Histoculturesmentioning

confidence: 99%

“…To define whether the observed galectin-1-mediated increase of HIV-1 replication in cells cultured in vitro can also take place in a cellular microenvironment such as secondary lymphoid organs, we used an established ex vivo histoculture lymphoid tissue model that supports HIV-1 infection without exogenous activation (27,30). Human lymphoid organ sections were prepared from tonsillar tissues and inoculated with HIV-1.…”

Section: Galectin-1 Increases Hiv-1 Infection In An Ex Vivo Lymphoid mentioning

confidence: 99%

Galectin-1 Acts as a Soluble Host Factor That Promotes HIV-1 Infectivity through Stabilization of Virus Attachment to Host Cells

Ouellet¹,

Mercier²,

Pelletier

et al. 2005

The Journal of Immunology

156

161

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The establishment of HIV type 1 (HIV-1) infection is initiated by the stable attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between virus-encoded gp120 and cell surface CD4, a number of distinct interactions influence binding of HIV-1 to host cells. In this study, we report that galectin-1, a dimeric β-galactoside-binding protein, promotes infection with R5, X4, and R5X4 variants. Galectin-1 acts as a soluble adhesion molecule by facilitating attachment of HIV-1 to the cell surface. This postulate is based on experiments where galectin-1 rendered HIV-1 particles more refractory to various agents that block HIV-1 adsorption and coreceptor binding (i.e., a blocking anti-CD4, soluble CD4, human anti-HIV-1 polyclonal Abs; stromal cell-derived factor-1α; RANTES). Experiments performed with the fusion inhibitor T-20 confirmed that galectin-1 is primarily affecting HIV-1 attachment. The relevance of the present findings for the pathogenesis of HIV-1 infection is provided by the fact that galectin-1 is abundantly expressed in the thymus and lymph nodes, organs that represent major reservoirs for HIV-1. Moreover, galectin-1 is secreted by activated CD8+ T lymphocytes, which are found in high numbers in HIV-1-positive patients. Therefore, it is proposed that galectin-1, which is released in an exocrine fashion at HIV-1 replication sites, can cross-link HIV-1 and target cells and promote a firmer adhesion of the virus to the cell surface, thereby augmenting the efficiency of the infection process. Overall, our findings suggest that galectin-1 might affect the pathogenesis of HIV-1 infection.

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“…Human tonsil histocultures were prepared as described. 77 Briefly, human tonsil tissues removed during routine tonsillectomy were received within 5 h of excision. The tonsils were washed thoroughly with medium containing antibiotics and then sectioned into 2-3 mm 2 blocks.…”

Section: Cells and Preparation Of Tonsil Tissue Blocksmentioning

confidence: 99%

The Nucleoside Triphosphate Diphosphohydrolase-1/CD39 Is Incorporated into Human Immunodeficiency Type 1 Particles, Where It Remains Biologically Active

Barat

Martin

Beaudoin

et al. 2007

Journal of Molecular Biology

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Human immunodeficiency virus type 1 (HIV-1) carries a variety of host proteins in addition to virus-encoded structural proteins, both in its envelope and inside the viral particle. Previous studies have reported that the HIV-1 life-cycle is affected by such virus-associated host cell surface proteins. The nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), also known as CD39, is a plasma membrane-bound ectoenzyme that hydrolyzes extracellular ATP and ADP to AMP. It has been shown that CD39 inhibits platelet function, and is thus a critical thromboregulatory molecule. We demonstrate here that host-derived CD39 is acquired by both laboratory-adapted and clinical variants of HIV-1 produced in cellular reservoirs of the virus. Moreover, purified CD39-bearing virions, but not isogenic viruses lacking CD39, display strong ATPase and ADPase activities. It is of particular interest that virions bearing this cellular enzyme can inhibit ADP-induced platelet aggregation, an effect blocked by an NTPDase inhibitor. On the basis of published and the present data on the functionality of human cellular proteins embedded within HIV-1, it can be proposed that these proteins might contribute to some of the immunologic deficiencies seen in infected individuals.

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Infection of human tonsil histocultures: A model for HIV pathogenesis

Cited by 174 publications

References 9 publications

Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

Galectin-1 Acts as a Soluble Host Factor That Promotes HIV-1 Infectivity through Stabilization of Virus Attachment to Host Cells

The Nucleoside Triphosphate Diphosphohydrolase-1/CD39 Is Incorporated into Human Immunodeficiency Type 1 Particles, Where It Remains Biologically Active

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