Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

Maher, Diane M.; Zhang, Zhi‐Qiang; Schacker, Timothy W.; Southern, Peter J.

doi:10.1369/jhc.4a6534.2005

Cited by 26 publications

(36 citation statements)

References 50 publications

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“…Normal " morphology equates to a range of variance away from the idealized state and, equally importantly, epithelial surface structure and barrier characteristics may change from normal to abnormal within 50 -100 m. Every piece of human tissue is different, and we have evidence from both histological and biochemical analyses that large differences can occur in adjacent regions on the surface of a single piece of tissue. 105,107,121 These same conclusions regarding tissue variability also apply to macaques. The critical point here is that, although variability in macaque FRT morphology undoubtedly affects macaque susceptibility to SIV infection, 63,122 -124 further insights into the specific events underlying HIV-1 transmission can only be derived by direct analysis of human premenopausal FRT.…”

Section: Practical Considerations For Experiments With Human Tissue Smentioning

confidence: 64%

“…We have used a multi-microscope approach to visualize a dynamic sequence of events that occurs when HIV-1 virions or HIV-1-infected cells are deposited onto intact human epithelial surfaces. 105,107 In many experiments, fluorescently labeled latex particles (0.1 and 4.0 m diameter spheres; Invitrogen: Molecular Probes, Eugene, OR; approximate representations of HIV-1 virions and HIV-1-infected lymphocytes, respectively) have been used to demonstrate that inert particles readily interact with mucosal surfaces in the FRT. Surface binding and tissue penetration were examined by time-lapse confocal microscopy, using fresh unfixed human tissues that contained live cells.…”

Section: Progression From Hiv-1 Exposure To Primary Hiv-1 Infectionmentioning

confidence: 99%

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Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

et al. 2011

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Section: Practical Considerations For Experiments With Human Tissue Smentioning

confidence: 64%

Section: Progression From Hiv-1 Exposure To Primary Hiv-1 Infectionmentioning

confidence: 99%

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

et al. 2011

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“…Expanded primary cell populations were determined to be fibroblasts by strong positive staining with antibodies directed against vimentin. No detectable staining with antibodies directed against cytokeratins was observed (30).…”

Section: Methodsmentioning

confidence: 96%

“…In earlier studies, we reported the potential of GAS to invade human primary tonsil epithelial cells (PHTF) in vitro (8). As we have continued to work with tonsil explants, we have identified considerable variability in the populations of primary cells that can be grown out (30). For these studies, we deliberately focused on PHTF as a potential source of TGF-␤1 because PHTF can be propagated in larger numbers to support biochemical analyses.…”

Section: Tgf-␤1 Enhances Expression Of ␣5 Integrin and Invasion Of Phtfmentioning

confidence: 99%

Streptococcal modulation of cellular invasion via TGF-β1 signaling

Wang

Southern

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Group A Streptococcus (GAS) and other bacterial pathogens are known to interact with integrins as an initial step in a complex pathway of bacterial ingestion by host cells. Efficient GAS invasion depends on the interaction of bound fibronectin (Fn) with integrins and activation of integrin signaling. TGF-␤1 regulates expression of integrins, Fn, and other extracellular matrix proteins, and positively controls the integrin signaling pathway. Therefore, we postulated that TGF-␤1 levels could influence streptococcal invasion of mammalian cells. Pretreatment of HEp-2 cells with TGF-␤1 increased their capacity to ingest GAS when the bacteria expressed fibronectin-binding proteins (M1 or PrtF1). Western blots revealed significant induction of ␣5 integrin and Fn expression by HEp-2 cells in response to TGF-␤1. Increased ingestion of streptococci by these cells was blocked by a specific inhibitor of the TGF-␤1 receptor I and antibodies directed against ␣5 integrin and Fn, indicating that increased invasion depends on TGF-␤1 up-regulation of both the ␣5 integrin and Fn. The capacity of TGF-␤1 to up-regulate integrin expression and intracellular invasion by GAS was reproduced in primary human tonsil fibroblasts, which could be a source of TGF-␤1 in chronically infected tonsils. The relationship between TGF-␤1 and GAS invasion was strengthened by the observation that TGF-␤1 production was stimulated in GASinfected primary human tonsil fibroblasts. These findings suggest a mechanism by which GAS induce a cascade of changes in mammalian tissue leading to elevated expression of the ␣5␤1 receptor, enhanced invasion, and increased opportunity for survival and persistence in their human host.integrin ͉ fibronectin ͉ fibronectin binding protein ͉ tonsils

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“…Tissue pieces in agarose were infected and processed as described (22,23). Alternatively, in some infections, cervical tissue was submerged in cell-free virus and then the tissue was cultured on collagen sponges at the gas-medium interface.…”

Section: Methodsmentioning

confidence: 99%

HIV binding, penetration, and primary infection in human cervicovaginal tissue

Maher

Schacker

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

115

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We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3-4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against ␤1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract.confocal microscopy ͉ female reproductive tissue ͉ HIV transmission ͉ organ culture ͉ tissue surface reconstruction

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Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

Cited by 26 publications

References 50 publications

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

Streptococcal modulation of cellular invasion via TGF-β1 signaling

HIV binding, penetration, and primary infection in human cervicovaginal tissue

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