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Interaction of cultured human Kupffer cells with HIV-infected CEM cells: an electron microscopic study
J L Gendrault1, A M Steffan, M P Schmitt
1Laboratoire de Virologie de la Faculté de Médecine, Unité INSERM 74, Strasbourg, France.
Abstract:
Evidence has accumulated indicating that macrophages could play a role in the physiopathology of AIDS. We recently demonstrated that cultured human liver macrophages, the so-called Kupffer cells (KC), are permissive for HIV. Their infection in vivo would lead these cells to constitute a target for the virus and a reservoir as well. Since they occupy a strategic position within the liver sinusoid, their opportunity to interact with blood-borne virus or already infected T lymphocytes may be very high. In the present study, we investigated the possibility for KC to be infected via HIV-infected CEM cells, a lymphoid cell line. Therefore, we cocultured both cell types for various times before fixing them for electron microscopy. Syncytia appeared within 20 h of infection as well as a large amount of virus particles. HIV in the way of budding was also easily observed. This has to be compared to the direct infection of KC with free virus which needs, at least, about 10 days to give the same results.
Insights
Human liver macrophages, Kupffer cells (KC), can be infected by HIV through direct contact with infected lymphoid cells. This interaction leads to rapid viral replication and syncytia formation, suggesting KC are a significant target and reservoir for HIV.
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Macrophages, specifically Kupffer cells (KC) in the liver, are implicated in Acquired Immunodeficiency Syndrome (AIDS) pathogenesis.
- Previous research demonstrated that cultured human Kupffer cells are permissive to Human Immunodeficiency Virus (HIV) infection.
- Kupffer cells' strategic location in liver sinusoids suggests frequent interaction with blood-borne viruses and infected lymphocytes.
Purpose of the Study:
- To investigate the susceptibility of Kupffer cells to HIV infection mediated by direct cell-to-cell contact.
- To compare the kinetics of HIV infection in Kupffer cells via infected lymphoid cells versus free virus.
Main Methods:
- Co-culturing of human Kupffer cells with HIV-infected CEM cells (a lymphoid cell line).
- Observation of cellular interactions and viral replication using electron microscopy at various time points.
- Assessment of syncytia formation and HIV particle budding.
Main Results:
- Syncytia formation and abundant HIV particles were observed within 20 hours of co-culturing Kupffer cells with HIV-infected CEM cells.
- HIV budding was readily detected in the co-culture system.
- This rapid infection contrasts with the approximately 10-day incubation period required for infection of Kupffer cells by cell-free HIV.
Conclusions:
- Kupffer cells can be efficiently infected by HIV through direct interaction with infected lymphoid cells.
- Cell-to-cell transmission of HIV to Kupffer cells is significantly faster than infection by free virus.
- These findings highlight Kupffer cells as a crucial target and potential reservoir for HIV, contributing to AIDS pathogenesis.