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Open Access

Cathepsin B and Cystatin A as Indicators of a Separate Apoptotic Pathway in HIV-1 Infection

  • Pål Voltersvik1,
  • Leif Bostad2,
  • AnneMa Dyrhol-Riise1, 3 and
  • Birgitta Åsjö1Email author
Retrovirology20052(Suppl 1):P11

https://doi.org/10.1186/1742-4690-2-S1-P11

Published: 8 December 2005

Keywords

CysteinePivotal RoleMultiple Regression AnalysisApoptotic PathwayCysteine Proteinase

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.

Notes

Authors’ Affiliations

(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

Copyright

© The Author(s) 2005

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