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Collection, Isolation, and Flow Cytometric Analysis of Human Endocervical Samples
Published on: July 6, 2014
In vitro HIV1 infection of human cervical tissue
J Palacio1, B E Souberbielle, R J Shattock
1Communicable Disease Unit, St George's Hospital Medical School, Tooting, London.
Insights
Human immunodeficiency virus (HIV) primarily infects macrophages in the cervix, not T cells, according to a new in vitro study. This research advances understanding of female genital tract HIV infection and prevention strategies.
Area of Science:
- Virology
- Immunology
- Gynecology
Background:
- Heterosexual intercourse is the primary mode of human immunodeficiency virus (HIV) transmission globally.
- HIV infection of the female genital tract and its primary cellular targets remain incompletely understood.
- Understanding cervical HIV infection is crucial for developing effective prevention and treatment strategies.
Purpose of the Study:
- To establish and utilize an in vitro model for studying HIV infection in the human adult cervix.
- To identify the primary cellular targets of HIV within the human cervix.
- To investigate the tropism of HIV strains responsible for cervical infection.
Main Methods:
- Human cervical mucosal explants were cultured in vitro.
- Explants were exposed to different HIV strains (macrophage-tropic and T-cell-tropic).
- HIV infection was detected using immunohistochemistry and in situ hybridization over a 7-day period.
Main Results:
- Only macrophage-tropic HIV (HIV-1Ba-L) successfully infected cervical explants.
- Infected cells were identified as macrophages located in the submucosa.
- T-cell-tropic HIV strains did not infect explants, despite the presence of CD4+/CD3+ T cells.
Conclusions:
- Macrophages, not T cells, are the primary cellular targets for HIV infection in the human cervix.
- This in vitro model provides a valuable tool for studying cervical HIV dynamics.
- The findings support further research into prophylactic and therapeutic strategies targeting macrophage infection in the cervix.
Abstract:
Heterosexual intercourse is the major mode of transmission of the human immunodeficiency virus (HIV) worldwide. Heterosexual transmission of HIV is particularly important in Africa and is increasing in the developed world. The mechanism of HIV infection of the female genital tract with HIV and subsequent events leading to clinical infection are not fully understood. In particular, the primary cellular targets of HIV infection in the female genital tract have not been determined. We have established an in vitro model for studying HIV infection of the human adult cervix by HIV. Human cervical mucosal explants were briefly exposed to HIV strains of different tropism and maintained in organ culture for 7 days. HIV infection detected by immunohistochemistry and in situ hybridization was only observed in cervical explants exposed to macrophage tropic strain HIV1Ba-L. HIV-infected cells were located in submucosa and had the morphology and distribution of macrophages. While CD4+/CD3+ T cells were still present at day 7 in the organ culture tissue, no infection of cervical explants was seen with T cell tropic strains even in the presence of phytohaemagglutinin and IL2. This model system will enable study of the dynamics of HIV infection of the human cervix and analysis of possible prophylactic or therapeutic strategies.
