PITTSBURGH, March 28 -- A new understanding about HIV transmission in women-- information that could lead to preventative strategies for this population -- will likely come from an organ culture model recently developed by researchers at the University of Pittsburgh's Graduate School of Public Health (GSPH). The new model, which is described in the April issue of the journal Nature Medicine, may result in breakthroughs such as barrier medications that prevent HIV from crossing through tissue linings of the female genital tract.
"The main route of HIV transmission has always been sexual, and heterosexuals are quickly becoming the largest HIV-positive population, particularly in third-world countries," said researcher Dr. Phalguni Gupta, Ph.D., professor in the department of infectious diseases and microbiology. "A model such as this is long overdue in understanding the virologic and host factors involved in HIV transmission in women."
According to Dr. Gupta, the new model will help researchers develop and test creams, suppositories or other medications to block the transmission of HIV.
Models used to date have demonstrated HIV transmission across a single layer of human cells grown specifically for that purpose. The new Pittsburgh model uses actual human tissue and thus closely mimics the stratified cell layers that are present at the sites of sexual transmission in women -- the vagina and outer portion of the cervix.
"This model provides the natural tissue architecture of the female genital tract, including epithelial cells, submucosa and immune cells, and it will allow us to effectively track transmission of HIV," said Dr. Gupta. It allows more rapid screening than did previous models, and by reducing the need for animals is more cost effective.
The new organ culture system involves placing a thumbnail-sized piece of squamous cervical tissue, with the epithelium layer on top, in the top chamber of a transwell device. HIV is added to the top of the tissue, and transmission of HIV is measured in the bottom chamber.
Scientists believe that the multilayer mucosal tissue structure of the female genital tract plays an important role in the sexual transmission of HIV. By allowing detailed study of the tissue structure, the model will enable researchers to determine which cells become infected initially, and how these cells interact with one another.
"The beauty of this model is that it allows us to test tissues from different areas of the human female genital organ to determine the role of each in transmission of HIV," said Dr. Gupta. In addition, tissue extracted at different stages of a woman's menstrual cycle can shed light on any effects hormonal and other changes might have on transmission.
Through further modification of the model scientists will be able to examine different genetic strains of HIV, as well as the effects of other sexually transmitted diseases on HIV transmission.
Using the new model, University of Pittsburgh researchers have already seen indications that cell-free virus is transmitted through the tissue structure much more efficiently than is cell-associated HIV, in which the virus remains inside a cell. Dr. Gupta and his colleagues are continuing research to further test these findings.
According to Dr. Gupta, plans also call for using the model to test rectal tissue in an effort to determine virologic and host factors in transmission between men.
This study was supported by the National Institutes of Health. It is a collaboration between Dr. Gupta's laboratory, including graduate student Kelly Brown Collins, and the laboratories of Daniel V. Landers, M.D., and Gregory J. Naus, M.D., of the Magee-Womens Hospital of the UPMC Health System.
For additional information about the Graduate School of Public Health at the University of Pittsburgh, access http://www.pitt.edu/~gsphhome/ . For information about UPMC Health System, access http://www.upmc.edu .
Journal
Nature Medicine