Cytotoxic T Lymphocyte Lysis Inhibited by Viable HIV Mutants

Immune evasion by the human immunodeficiency virus (HIV) is unexplained but may involve the mutation of viral antigens. When cytotoxic T lymphocytes engaged CD4-positive cells that were acutely infected with HIV bearing natural variant epitopes in reverse transcriptase, substantial inhibition of specific antiviral lysis was observed. Mutant viruses capable of these transactive effects could facilitate the persistence of a broad range of HIV variants in the face of an active and specific immune response.

[1]  J. Coffin Lines drawn in epitope wars , 1995, Nature.

[2]  P. Klenerman,et al.  Immunogenic HIV variant peptides that bind to HLA-B8 can fail to stimulate cytotoxic T lymphocyte responses. , 1995, Journal of immunology.

[3]  Paul Kellam,et al.  Convergent combination therapy can select viable multidrug-resistant HIV-1 in vitro , 1993, Nature.

[4]  Paul M. Allen,et al.  Partial T cell signaling: Altered phospho-ζ and lack of zap70 recruitment in APL-induced T cell anergy , 1994, Cell.

[5]  Nigel Bosworth,et al.  Scintillation proximity assay , 1989, Nature.

[6]  P. Klenerman,et al.  The effects of natural altered peptide ligands on the whole blood cytotoxic T lymphocyte response to human immunodeficiency virus , 1995, European journal of immunology.

[7]  L. Samelson,et al.  Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists , 1995, Science.

[8]  W. Paul Can the immune response control HIV infection? , 1995, Cell.

[9]  P. Illei,et al.  Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements. , 1994, The Journal of general virology.

[10]  M. Bevan,et al.  Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells , 1993, The Journal of experimental medicine.

[11]  A. Sette,et al.  Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells , 1994, Nature.

[12]  H. Temin,et al.  Spontaneous variation and synthesis in the U3 region of the long terminal repeat of an avian retrovirus , 1982, Journal of virology.

[13]  H. Temin,et al.  Retrovirus variation and reverse transcription: abnormal strand transfers result in retrovirus genetic variation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Andreas Meyerhans,et al.  Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations , 1989, Cell.

[15]  J. Eberle,et al.  A new method for measuring reverse transcriptase activity by ELISA. , 1992, Journal of virological methods.

[16]  U. Koszinowski,et al.  Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein , 1991, Cell.

[17]  L. Comstock,et al.  The tac promoter: a functional hybrid derived from the trp and lac promoters. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Martin A. Nowak,et al.  Antigenic oscillations and shifting immunodominance in HIV-1 infections , 1995, Nature.

[19]  W. James,et al.  A rat CD4 mutant containing the gp120-binding site mediates human immunodeficiency virus type 1 infection , 1993, The Journal of experimental medicine.

[20]  A. Townsend,et al.  Antigen recognition by class I-restricted T lymphocytes. , 1989, Annual review of immunology.

[21]  R. Young,et al.  Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S D Kemp,et al.  Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). , 1989, Science.

[23]  M. Bevan The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens , 1975, The Journal of experimental medicine.

[24]  P. Allen,et al.  Tickling the TCR: selective T-cell functions stimulated by altered peptide ligands. , 1993, Immunology today.

[25]  P. Simmonds,et al.  Detection, quantification and sequencing of HIV-1 from the plasma of seropositive individuals and from factor VIII concentrates. , 1991, AIDS.

[26]  J. Levy,et al.  Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main immunogenic region of the human immunodeficiency virus 1 NEF protein , 1994, The Journal of experimental medicine.

[27]  B. Larder,et al.  Infectious potential of human immunodeficiency virus type 1 reverse transcriptase mutants with altered inhibitor sensitivity. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Charles R. M. Bangham,et al.  Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition , 1991, Nature.

[29]  R. Koup Virus escape from CTL recognition , 1994, The Journal of experimental medicine.