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Fas antigen expression and apoptosis of lymphocytes in macaques infected with simian immunodeficiency virus strain
T Iida1, T Igarashi, H Ichimura
1Department of Microbiology, Kyoto Prefectural University of Medicine, Japan.
Abstract:
To investigate the role of apoptosis in the pathogenesis of HIV infection we used macaques infected with simian immunodeficiency virus (SIV) as a primate model and examined the characteristics of the apoptosis of lymphocytes in SIV mac-infected macaques. In vitro apoptosis was more strongly induced in peripheral blood mononuclear cells (PBMC) from SIV mac239-infected macaques than those from uninfected controls. We found that the frequency of Fas antigen-positive cells was higher in PBMC from SIV mac-infected macaques than from uninfected controls, and in vitro apoptosis of PBMC was suppressed by an inhibitor of the interleukin-1 beta converting enzyme (ICE) family proteases. In biopsied lymph nodes, the number of apoptotic nuclei in T cell-dependent areas was higher in SIV mac-infected macaques than in uninfected controls. A higher number of apoptotic nuclei in lymph nodes of SIV mac-infected macaques was observed in the stage of persistent general lymphadenopathy than in those with AIDS-related complex, while there was no significant difference in the extent of apoptosis of cultured PBMC among the SIV mac-infected macaques. These results suggest that in vitro apoptosis is mediated by the Fas/Fas ligand and ICE system and that apoptosis in lymph nodes may be more closely related to the stage of SIV mac infection than is that of cultured PBMC.
Insights
Simian immunodeficiency virus (SIV) infection in macaques shows increased lymphocyte apoptosis, particularly in lymph nodes during early stages. This apoptosis is linked to the Fas/Fas ligand and ICE protease systems.
Area of Science:
- Immunology
- Virology
- Pathogenesis
Background:
- Human immunodeficiency virus (HIV) infection leads to immune system destruction.
- Apoptosis, or programmed cell death, is implicated in lymphocyte depletion during HIV pathogenesis.
- Simian immunodeficiency virus (SIV) in macaques serves as a relevant model for studying HIV infection.
Purpose of the Study:
- To investigate the role and characteristics of lymphocyte apoptosis in SIV-infected macaques.
- To explore the mechanisms underlying apoptosis in SIV infection, including the Fas/Fas ligand and ICE protease pathways.
- To correlate apoptosis levels with the stage of SIV mac infection.
Main Methods:
- Used SIV-infected macaques as a primate model.
- Examined apoptosis in peripheral blood mononuclear cells (PBMC) and lymph node biopsies.
- Assessed Fas antigen expression on PBMC.
- Utilized an inhibitor of interleukin-1 beta converting enzyme (ICE) family proteases to study apoptosis.
- Compared apoptosis in macaques with persistent general lymphadenopathy versus those with AIDS-related complex.
Main Results:
- In vitro apoptosis was significantly higher in PBMC from SIV-infected macaques compared to controls.
- Fas antigen-positive cells were more frequent in PBMC of SIV-infected macaques.
- In vitro PBMC apoptosis was inhibited by an ICE protease inhibitor.
- Lymph nodes of SIV-infected macaques showed increased apoptotic nuclei, especially during persistent lymphadenopathy.
- Apoptosis levels in cultured PBMC did not significantly differ among SIV-infected macaques.
Conclusions:
- In vitro apoptosis in SIV infection is mediated by the Fas/Fas ligand and ICE protease systems.
- Lymph node apoptosis correlates with the stage of SIV mac infection, unlike cultured PBMC apoptosis.
- Apoptosis plays a significant role in the pathogenesis of SIV infection, particularly in lymph nodes.