This article is part of the supplement: 2005 International Meeting of The Institute of Human Virology
Poster presentation
Cathepsin B and Cystatin A as Indicators of a Separate Apoptotic Pathway in HIV-1 Infection
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* Corresponding author: Birgitta Åsjö birgitta.asjo@gades.uib.no
1 Center f. Res. in Virology, The Gade Institute, Univ. of Bergen, Bergen, Norway
2 Dept. of Pathology, Bergen, Norway
3 Inst. of Medicine Haukeland University Hospital, Bergen, Norway
Retrovirology 2005, 2(Suppl 1):P11 doi:10.1186/1742-4690-2-S1-P11
The electronic version of this article is the complete one and can be found online at:
| Published: | 8 December 2005 |
©
Poster presentation
Apoptosis has been proposed to explain the dysfunction in HIV-1 infection and FAS has been given a pivotal role. However, apoptosis in lymphoid follicles has also been explained by a follicular dendritic cell (FDC) dependent pathway regulated by a cathepsin-dependent endonuclease activity in germinal centre (GC) cells. Cystatin A is present in FDCs and is a natural inhibitor of cysteine proteinase, as Cathepsin B. As yet, the Cystatin A and Cathepsin B interaction in HIV-1 infection has not been studied.
Methods
Tonsillar tissue was obtained from 20 patients at various stages of HIV-1 infection and 10 controls. Eleven of the patients received HAART for 48 weeks. Cathepsin B, Cystatin A, FAS(CD95) and HIV-1 p24 in the GC cells were analyzed by immunohistochemi-cal staining. Cathepsin B/Cystatin A ratios were calculated for controls and for patients before and after 48 weeks of therapy.
Results
Cathepsin B/Cystatin A ratio was 2-fold higher in patients as compared to controls; 1.03 and 0.43, respectively. After 48 weeks of therapy, this ratio was normalized (0.32). In patients, Cathepsin B correlated negatively with Cystatin A (r = -0.686, p = 0.002), and both markers correlated with the p24 antigen; r = 0.777 (p = 0.001) and r = -0.622 (p = 0.013), respectively. In multiple regression analysis presence of p24 antigen could not fully explain this relationship. There was no correlation with FAS(CD 95) for these parameters.
Conclusion
A 2-fold higher Cathepsin B/Cystatin A ratio was found in patients before HAART, suggesting a HIV-1 driven cathepsin-dependent pathway of apoptosis. Thus, Cathepsin B and Cystatin A possibly represent an apoptotic pathway distinguishable from the FAS-FAS Ligand pathway.