Cervico‐Vaginal Tissue Ex Vivo as a Model to Study Early Events in HIV‐1 Infection

Abstract

Vaginal intercourse remains the most prevalent route of infection of women. In spite of many efforts the detailed mechanisms of HIV-1 transmission in the female lower genital tract, remain largely unknown. With all the obvious restrictions on studying these mechanisms in humans, their understanding depends on the development of adequate experimental models. Isolated cell cultures do not faithfully reproduce important aspects of cell-cell interactions in living tissues and tissue responses to pathogens. Explants and other types of ex vivo tissue models serve as a bridge between cell culture and tissues in vivo. Here, we discuss various cervico-vaginal tissue models and their use in studying HIV vaginal transmission and consider future directions of such studies.

The Molecular Characterization of Intestinal Explant HIV Infection Using Polymerase Chain Reaction-Based Techniques

“…6 An advantage of this system over cell culture is that, at time of viral challenge, cellular architecture is maintained, mimicking to a greater extent the environment found in vivo at the time of infection. 7 Furthermore, rectal explant tissues do not need artificial stimulation with IL-2 or PMA for productive infection with HIV-1. 8 Gut-associated lymphoid tissue (GALT) has many components of the lymphatic system including CD4 + /CCR5 + -activated T cells, which are targeted by HIV-1 infection.…”

HIV Transmission

“…Much of this has been summarized in recent reviews (Hladik and McElrath 2008;Wira and Veronese 2011). Although increasing attention in recent years has been paid to penile (Fischetti et al 2009;Dinh et al 2011) and gastrointestinal (Fletcher et al 2006;Grivel et al 2007;Shen et al 2009Shen et al , 2010 explant models, most information (Collins et al 2000;Greenhead et al 2000;Hu et al 2004;Maher et al 2005;Hladik et al 2007;Saba et al 2010;Merbah et al 2011), can be correlated with in situ studies of primate infection by SIV (Haase 2010). Hladik and colleagues (2007) described a human vaginal organ explant culture system that involved the physical separation of vaginal epithelium from underlying stroma.…”

Immunofluorescence Analysis of Human Endocervical Tissue Explants Infected with Neisseria gonorrhoeae

“…Cervical tissues (~5 g/piece) from patients undergoing voluntary hysterectomy are obtained in sterile DMEM with 1x penicillin/streptomycin (see Recipes) at 4 °C within 24 h post-surgery (Merbah et al ., 2011), coordinated by National Disease Research Interchange (NDRI) (an institutional review board must approve the research protocol involving human tissues. Please verify with your own institutional review board for the regulation).…”

“…This work was supported by NIH grants (RO1 AI068888, R21 AI103797, and RO1 AI123340 to WS and DCS). This protocol was partially adapted from previously published work by Merbah et al (2011) and Schürch et al . (1978).…”