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Study of HIV-1 Transmission across Cervical Mucosa to Tonsil Tissue Cells using an Organ Culture

Authors

  • Jackeline Soto-Rivera,

    1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Bruce K. Patterson,

    1. Departments of Pathology and Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA
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  • Yue Chen,

    1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Chengli Shen,

    1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Deena Ratner,

    1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Ming Ding,

    1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Ashwin Tumne,

    1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Phalguni Gupta

    Corresponding author
    • Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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Correspondence

Phalguni Gupta, Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

E-mail: pgupta1@pitt.edu

Abstract

Problem

SIV model indicates that upon traversing the cervicovaginal mucosa, SIV/SIV-infected cells migrate to regional lymph nodes where active replication occurs prior to systemic virus dissemination. The purpose of the study is to develop a model to study early HIV-1 transmission events that occur after crossing the cervical mucosa into regional lymph nodes.

Methods of study

We developed an organ culture model combining intact cervical tissue explants and tonsil tissue cells as the surrogate draining lymphoid tissue. Viral replication was measured by HIV-1 p24 production, quantification of viral DNA and viral RNA expression in tonsil cells.

Results

In this combined organ culture model, transmission of cell-free and cell-associated R5- and X4-tropic HIV-1 through the cervical mucosa to tonsilar cells was observed as determined by HIV-1 p24 in culture supernatant, and the presence of HIV-1 proviral DNA, HIV-1 p24 gag protein in CD4+, CD11c+, CD68+ cells, and expression of HIV-1 mRNA expressing CD45RO+ CD4 T cells in tonsil cells. Furthermore, co-receptor usage of HIV-1 in tonsil cells correlated with inoculating virus tropism.

Conclusions

Our combined cervix–tonsil organ culture could serve as an experimental model to study the earliest stages of HIV-1 transmission through cervicovaginal mucosa to its proximal lymph nodes.

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