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Study of HIV ‐1 Transmission across Cervical Mucosa to Tonsil Tissue Cells using an Organ Culture
Author(s) -
SotoRivera Jackeline,
Patterson Bruce K.,
Chen Yue,
Shen Chengli,
Ratner Deena,
Ding Ming,
Tumne Ashwin,
Gupta Phalguni
Publication year - 2013
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12018
Subject(s) - tonsil , tropism , organ culture , lymph , palatine tonsil , virology , biology , cervix , lymphatic system , viral replication , cervical lymph nodes , cell culture , virus , pathology , immunology , medicine , in vitro , cancer , biochemistry , genetics , metastasis
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 R 5‐ and X 4‐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 CD 4 + , CD 11c + , CD 68 + cells, and expression of HIV ‐1 mRNA expressing CD 45RO + CD 4 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.