Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis

Journal of Clinical Investigation

Volumn 111, Issue 10, 2003, Pages 1547-1554

  Lum, Julian J ^a   Cohen, Oren J ^b   Nie, Zilin ^a,c   Weaver, Joel G ^c   Gomez, Timothy S ^c   Yao, Xiao Jian ^d   Lynch, David ^e   Pilon, André A ^a   Hawley, Nanci ^c   Kim, John E ^f   Chen, Zhaoxia ^f   Montpetit, Michael ^f   Sanchez Dardon, Jaime ^a   Cohen, Eric A ^d   Badley, Andrew D ^a,c  

^a OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c MAYO CLINIC   (United States)

^d UNIVERSITÉ DE MONTRÉAL   (Canada)

^e AMGEN INC   (United States)

^f HEALTH CANADA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DNA FRAGMENT; PROCASPASE 3; PROCASPASE 8; UNCLASSIFIED DRUG; VIRUS PROTEIN; VPR PROTEIN; CASPASE; PEPTIDE FRAGMENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL KILLING; CONTROLLED STUDY; DISEASE COURSE; FLOW CYTOMETRY; GENE; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE DEFICIENCY; IMMUNOPATHOLOGY; LIVER MITOCHONDRION; LONG TERM CARE; LONG TERM NONPROGRESSIVE HIV INFECTION; MEMBRANE POTENTIAL; MITOCHONDRIAL MEMBRANE; MOUSE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DOMAIN; T LYMPHOCYTE; VESICULAR STOMATITIS VIRUS; VIRUS REPLICATION; VPRR77Q GENE; AMINO ACID SUBSTITUTION; CD4 LYMPHOCYTE COUNT; CELL SURVIVAL; DOSE RESPONSE; DRUG EFFECT; ENZYMOLOGY; GENE FREQUENCY; GENETICS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; LEUKEMIA CELL LINE; METABOLISM; MITOCHONDRION; MUTATION; VIROLOGY;

AMINO ACID SUBSTITUTION; APOPTOSIS; CASPASES; CD4 LYMPHOCYTE COUNT; CELL SURVIVAL; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE FREQUENCY; GENE PRODUCTS, VPR; HIV INFECTIONS; HIV LONG-TERM SURVIVORS; HIV-1; HUMANS; JURKAT CELLS; MITOCHONDRIA; MUTATION; PEPTIDE FRAGMENTS; T-LYMPHOCYTES; VESICULAR STOMATITIS-INDIANA VIRUS;

EID: 33044503759     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI16233     Document Type: Article

References (29)

1. Zhang, L., Huang, Y., Yuan, H., Tuttleton, S., and Ho, D.D. 1997. Genetic characterization of vif, vpr, and vpu sequences from long-term survivors of human immunodeficiency virus type 1 infection. Virology. 228:340-349.
2. Buchbinder, S.P., Katz, M.H., Hessol, N.A., O'Malley, P.M., and Holmberg, S.D. 1994. Long-term HIV-1 infection without immunologic progression. AIDS. 8:1123-1128.
3. Cohen, O.J., et al. 1997. Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors. J. Clin. Invest. 100:1581-1589.
4. Deacon, N.J., et al. 1995. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science. 270:988-991.
5. Kaslow, R.A., et al. 1996. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat. Med. 2:405-411.
6. - T cells: implications for the development of therapeutic strategies. Proc. Natl. Acad. Sci. U.S.A. 98:253-258.
7. Matsuda, Z., Yu, X., Yu, Q.C., Lee, T.H., and Essex, M. 1993. A virion-specific inhibitory molecule with therapeutic potential for human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U. S. A. 90:3544-3548.
8. Levy, D.N., Refaeli, Y., MacGregor, R.R., and Weiner, D.B. 1994. Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U. S. A. 91:10873-10877.
9. Stewart, S.A., Poon, B., Jowett, J.B., and Chen, I.S. 1997. Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest. J. Virol. 71:5579-5592.
10. Patel, C.A., Mukhtar, M., and Pomerantz, R.J. 2000. Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells. J. Virol. 74:9717-9726.
11. Macreadie, I.G., et al. 1995. A domain of human immunodeficiency virus type 1 Vpr containing repeated H(S/F)RIG amino acid motifs causes cell growth arrest and structural defects. Proc Natl. Acad. Sci. U. S. A. 92:2770-2774.
12. Jacotot, E., et al. 2001. Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein rR and Bcl-2. J. Exp. Med. 193:509-519.
13. Jacotot, E., et al. 2000. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J. Exp. Med. 191:33-46.
14. Yao, X.J., et al. 1998. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells. J. Virol. 72:4686-4693.
15. Phenix, B.N., Lum, J.J., Nie, Z., Sanchez-Dardon, J., and Badley, A. D. 2001. Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss. Blood. 98:1078-1085.
16. Baudouin, F., Sarda, M.N., Goguel, A., and Bene, M.C. 1999. Multicenter study of reference stabilized human blood for lymphocyte immunophenotyping quality control in flow cytometry. GEIL. Cytometry 38:127-132.
17. + cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry. 34:61-70.
18. Wang, B., et al. 1996. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair: in vivo evolution of vpr quasispecies in blood and plasma. Virology. 223:224-232.
19. Kobayashi, N., et al. 1990. Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc. Natl. Acad. Sci. U. S. A. 87:9620-9624.
20. Badley, A.D., Pilon, A.A., Landay, A., and Lynch, D.H. 2000. Mechanisms of HIV-associated lymphocyte apoptosis. Blood. 96:2951-2964.
21. Estaquier, J., et al. 1994. Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. Proc. Natl. Acad. Sci. U. S. A. 91:9431-943S.
22. +-T-cell counts, spontaneous apoptosis, and Fas expression in peripheral blood mononuclear cells obtained from human immunodeficiency virus type 1-infected subjects. Clin. Diagn. Lab. Immunol. 4:736-741.
23. - cells during human immunodeficiency virus tvpe 1 infection - correlation with clinical progression, viral load, and loss of humoral immunity. Virology. 238:180-188.
24. Badley, A.D., et al. 1999. Dynamic correlation of apoptosis and immune activation during treatment of HIV infection. Cell Death Differ. 6:420-432.
25. Badley, A.D., et al. 1998. In vivo analysis of Fas/FasL interactions in HIV-infected patients. J. Clin. Invest. 102:79-87.
26. Liegler, T.J., et al. 1998. Diminished spontaneous apoptosis in lymphocytes from human immunodeficiency virus-infected long-term nonprogressors. J. Infect. Dis. 178:669-679.
27. Wasmuth, J.C., et al. 2000. Prediction of imminent complications in HIV-1-infected patients by markers of lymphocyte apoptosis. J. Acquire. Immune Defic. Syndr. 23:44-51.
28. Franceschi, C., et al. 1997. Phenotypic characteristics and tendency to apoptosis of peripheral blood mononuclear cells from HIV+ long term non progressors. Cell Death Differ. 4:815-823.
29. Yasuda, J., Miyao, T., Kamata, M., Aida, Y., and Iwakura, Y. 2001. T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene. Virology. 285:181-192.