The Role of Interleukin-converting Enzyme in Fas-mediated Apoptosis in HIV-1 Infection

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1998 Feb 14

PMID 9421482

Citations 7

Authors

E M Sloand

J P Maciejewski

T Sato

J Bruny

P Kumar

S Kim

F F Weichold

N S Young

Affiliations

Soon will be listed here.

Abstract

Apoptosis of CD4+ lymphocytes is partially responsible for the depletion of these cells in HIV-infected individuals. CD4+ lymphocytes from HIV-1-infected patients express higher membrane levels of the Fas receptor, and are particularly susceptible to apoptosis after Fas triggering. IL-1beta- converting enzyme (ICE) is a key enzyme of the apoptotic machinery involved in Fas-mediated apoptosis of normal lymphocytes. The role of ICE in mediating the increased susceptibility of CD4+ lymphocytes from HIV-1-infected patients to apoptosis has not been examined. In this study, we found that ICE mRNA was present in T cells from both HIV-1-infected patients and controls. Active ICE proteins, p10 and p20, were demonstrated by immunoblot in lymphocytes from HIV-1-infected patients and in normal lymphocytes after treatment with Fas agonist, CH11 mAb. Cocultivation of lymphocytes from HIV-1-infected persons with Fas antagonist, antibody ZB4, resulted in decreased expression of ICE protein in lymphocytes from HIV-infected patients, and decreased apoptosis. Similar effects were obtained when cells were treated with synthetic ICE inhibitors, which blocked apoptosis in response to Fas triggering. When CD4+ and CD8+ cells were sorted by flow cytometry and analyzed by reverse transcriptase PCR, ICE mRNA was present in both CD8+ and CD4+ cells. However, flow cytometric analysis of lymphocytes with intracellular staining for ICE demonstrated ICE protein in the CD4+ but not the CD8+ cell fraction derived from blood of HIV-1-infected patients. These data suggest that activation of ICE occurs in vivo in CD4+ lymphocytes from HIV-1-infected individuals, and may account for the increased susceptibility of CD4+ cells to apoptosis.

Citing Articles

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.

Laforge M, Silvestre R, Rodrigues V, Garibal J, Campillo-Gimenez L, Mouhamad S J Clin Invest. 2018; 128(4):1627-1640.

PMID: 29553486 PMC: 5873886. DOI: 10.1172/JCI95127.

Some findings of FADD knockdown in inhibition of HIV-1 replication in Jurkat cells and PBMCs.

Wang X, Tan J, Zhao J, Ragupathy V, Haleyurgirisetty M, Hewlett I Mol Cell Biochem. 2014; 393(1-2):181-90.

PMID: 24752353 DOI: 10.1007/s11010-014-2058-7.

The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or....

Priceputu E, Rodrigue I, Chrobak P, Poudrier J, Mak T, Hanna Z J Virol. 2005; 79(10):6377-91.

PMID: 15858021 PMC: 1091671. DOI: 10.1128/JVI.79.10.6377-6391.2005.

Correlates of immune activation marker changes in human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women who use illicit drugs.

Landay A, Benning L, Bremer J, Weiser B, Burger H, Nowicki M J Infect Dis. 2003; 188(2):209-18.

PMID: 12854075 PMC: 3164115. DOI: 10.1086/376509.

Effects of antiretroviral drugs on human immunodeficiency virus type 1-induced CD4(+) T-cell death.

Estaquier J, Lelievre J, Petit F, Brunner T, Moutouh-de Parseval L, Richman D J Virol. 2002; 76(12):5966-73.

PMID: 12021329 PMC: 136220. DOI: 10.1128/jvi.76.12.5966-5973.2002.

References

Kuida K, Lippke J, Ku G, Harding M, Livingston D, Su M . Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science. 1995; 267(5206):2000-3. DOI: 10.1126/science.7535475. View

Brunner T, Mogil R, LaFace D, Yoo N, Mahboubi A, Echeverri F . Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature. 1995; 373(6513):441-4. DOI: 10.1038/373441a0. View

Los M, van de Craen M, Penning L, Schenk H, Westendorp M, Baeuerle P . Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature. 1995; 375(6526):81-3. DOI: 10.1038/375081a0. View

Faucheu C, Diu A, Chan A, Blanchet A, Miossec C, Herve F . A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells. EMBO J. 1995; 14(9):1914-22. PMC: 398290. DOI: 10.1002/j.1460-2075.1995.tb07183.x. View

Maciejewski J, Selleri C, Anderson S, Young N . Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro. Blood. 1995; 85(11):3183-90. View

Katsikis P, Wunderlich E, Smith C, Herzenberg L . Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals. J Exp Med. 1995; 181(6):2029-36. PMC: 2192074. DOI: 10.1084/jem.181.6.2029. View

Tewari M, Quan L, ORourke K, Desnoyers S, Zeng Z, Beidler D . Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995; 81(5):801-9. DOI: 10.1016/0092-8674(95)90541-3. View

Kumar S, Harvey N . Role of multiple cellular proteases in the execution of programmed cell death. FEBS Lett. 1995; 375(3):169-73. DOI: 10.1016/0014-5793(95)01186-i. View

Nicholson D, Ali A, Thornberry N, Vaillancourt J, Ding C, Gallant M . Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995; 376(6535):37-43. DOI: 10.1038/376037a0. View

10.

Munday N, Vaillancourt J, Ali A, Casano F, Miller D, Molineaux S . Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases. J Biol Chem. 1995; 270(26):15870-6. DOI: 10.1074/jbc.270.26.15870. View

11.

Dhawan S, Heredia A, Wahl L, Epstein J, Meltzer M, Hewlett I . Interferon-gamma-induced downregulation of CD4 inhibits the entry of human immunodeficiency virus type-1 in primary monocytes. Pathobiology. 1995; 63(2):93-9. DOI: 10.1159/000163939. View

12.

Oyaizu N, Pahwa S . Role of apoptosis in HIV disease pathogenesis. J Clin Immunol. 1995; 15(5):217-31. DOI: 10.1007/BF01540879. View

13.

Mashima T, Naito M, Fujita N, Noguchi K, Tsuruo T . Identification of actin as a substrate of ICE and an ICE-like protease and involvement of an ICE-like protease but not ICE in VP-16-induced U937 apoptosis. Biochem Biophys Res Commun. 1995; 217(3):1185-92. DOI: 10.1006/bbrc.1995.2894. View

14.

Lippke J, Gu Y, Sarnecki C, Caron P, Su M . Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32. J Biol Chem. 1996; 271(4):1825-8. DOI: 10.1074/jbc.271.4.1825. View

15.

Piasecki E, Ledwon T, INGLOT A, Knysz B, Simon K, Inglot M . Interferon and tumor necrosis factor responses of HIV+ patients as markers for monitoring of the AIDS progression. Arch Immunol Ther Exp (Warsz). 1994; 42(5-6):439-45. View

16.

Martin S, Amarante-Mendes G, Shi L, Chuang T, Casiano C, OBrien G . The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO J. 1996; 15(10):2407-16. PMC: 450172. View

17.

Selleri C, Sato T, Del Vecchio L, Luciano L, Barrett A, Rotoli B . Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-alpha in chronic myelogenous leukemia. Blood. 1997; 89(3):957-64. View

18.

Sloand E, Young N, Kumar P, Weichold F, Sato T, Maciejewski J . Role of Fas ligand and receptor in the mechanism of T-cell depletion in acquired immunodeficiency syndrome: effect on CD4+ lymphocyte depletion and human immunodeficiency virus replication. Blood. 1997; 89(4):1357-63. View

19.

Chinnaiyan A, Woffendin C, Dixit V, Nabel G . The inhibition of pro-apoptotic ICE-like proteases enhances HIV replication. Nat Med. 1997; 3(3):333-7. DOI: 10.1038/nm0397-333. View

20.

Naito M, Nagashima K, Mashima T, Tsuruo T . Phosphatidylserine externalization is a downstream event of interleukin-1 beta-converting enzyme family protease activation during apoptosis. Blood. 1997; 89(6):2060-6. View