Faculty Opinions recommendation of Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses.

2001 ◽  
Author(s):  
Mary Carrington
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hla B27 ◽  
Lymphocyte Responses ◽  
Hiv 1

scholarly journals Clustered Mutations in HIV-1 Gag Are Consistently Required for Escape from Hla-B27–Restricted Cytotoxic T Lymphocyte Responses

2001 ◽  
Vol 193 (3) ◽  
pp. 375-386 ◽  
Author(s):  
Anthony D. Kelleher ◽  
Chad Long ◽  
Edward C. Holmes ◽  
Rachel L. Allen ◽  
Jamie Wilson ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Phylogenetic Analyses ◽  
High Viral Load ◽  
Hla B27 ◽  
Gag Protein ◽  
Leukocyte Antigen ◽  
Viral Loads ◽  
Lymphocyte Responses ◽  
Hiv 1

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263–272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.

Kinetics of HIV-1 specific cytotoxic T lymphocyte responses and viral load in the natural history of HIV-1 infection

1997 ◽  
Vol 56 ◽  
pp. 25
Author(s):  
O. Pontesilli ◽  
M.R. Klein ◽  
S.R. Kerkhof-Garde ◽  
N. Pakker ◽  
F. de Wolf ◽  
...  
Keyword(s):  
Viral Load ◽  
Natural History ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
History Of ◽  
Lymphocyte Responses ◽  
Kinetics Of ◽  
Hiv 1

Cytotoxic T lymphocyte responses in HIV-1-infected long-term nonprogressors: lessons for vaccine design

2008 ◽  
Vol 2 (4) ◽  
pp. 351-361 ◽  
Author(s):  
Marjon Navis ◽  
Frank Miedema ◽  
Hanneke Schuitemaker
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Vaccine Design ◽  
Lymphocyte Responses ◽  
Hiv 1

HIV-1 Env-specific cytotoxic T-lymphocyte responses in exposed, uninfected Kenyan sex workers

AIDS ◽  
2004 ◽  
Vol 18 (15) ◽  
pp. 2087-2089 ◽  
Author(s):  
Rupert Kaul ◽  
John Rutherford ◽  
Sarah L Rowland-Jones ◽  
Joshua Kimani ◽  
James Isaiah Onyango ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Sex Workers ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Responses ◽  
Exposed Uninfected ◽  
Hiv 1

Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection*

1999 ◽  
Vol 97 (6) ◽  
pp. 707-718 ◽  
Author(s):  
David A. PRICE ◽  
Chris A. O'CALLAGHAN ◽  
Joseph A. WHELAN ◽  
Philippa J. EASTERBROOK ◽  
Rodney E. PHILLIPS
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Evolution ◽  
Case Series ◽  
Effector Cells ◽  
Lymphocyte Responses ◽  
Hiv 1

Efforts to develop immune-based therapies for HIV infection have been impeded by incomplete definition of the immunological correlates of protection. Despite many precedents demonstrating that CD8+ cytotoxic T lymphocytes are key mediators of protective anti-viral immunity in non-human animal models, direct evidence that these effector cells control viral replication in HIV-1 infection has remained elusive. The first part of this paper describes a detailed immunological and genetic study founded on evolutionary considerations. Following infection with HIV-1, virus variants which escaped recognition by autologous cytotoxic T lymphocytes were shown to possess a selection advantage within the host environment. Cytotoxic T lymphocytes therefore exert anti-viral pressure in vivo. This observation provides compelling evidence that cytotoxic T lymphocytes comprise a significant element of anti-retroviral immunity. Subsequently, the quantification of peripheral cytotoxic T lymphocyte frequencies utilizing peptide–(human leucocyte antigen class I) tetrameric complexes is described. Five patients with qualitatively similar immunodominant cytotoxic T lymphocyte responses during symptomatic primary HIV-1 infection were studied longitudinally. Expansions of virus-specific CD8+ lymphocytes comprising up to 2% of the total CD8+ T cell population were observed in the acute phase of infection. Antigenic load was identified as an important determinant of circulating HIV-1-specific CD8+ lymphocyte levels; however, significant numbers of such cells were also found to persist following prolonged therapeutic suppression of plasma viraemia. In addition, an analysis of antigenic sequence variation with time in this case series suggests that the early administration of combination anti-retroviral therapy may limit HIV-1 mutational escape from host cytolytic specificities. The implications of these preliminary data are discussed. The data presented suggest that vaccination protocols should aim to elicit vigorous cytotoxic T lymphocyte responses to HIV-1. Attempts to stimulate polyvalent responses to mutationally intolerant epitopes are likely to be most effective. Optimal management of HIV-1 infection requires an understanding of dynamic host–virus interactions, and may involve strategies designed to enhance cytotoxic T lymphocyte activity following periods of anti-retroviral drug therapy.

scholarly journals Persistent Antibody Responses but Declining Cytotoxic T-Lymphocyte Responses to Multiple Human Immunodeficiency Virus Type 1 Antigens in a Long-Term Nonprogressing Individual with a Defective p17 Proviral Sequence and No Detectable Viral RNA Expression

1998 ◽  
Vol 72 (4) ◽  
pp. 3472-3474 ◽  
Author(s):  
James M. Binley ◽  
Xia Jin ◽  
Yaoxing Huang ◽  
Linqi Zhang ◽  
Yunzhen Cao ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antibody Responses ◽  
The Past ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Long-term nonprogressor AD-18 has been infected with human immunodeficiency virus type 1 (HIV-1) for at least 16 years. During the past 5 years, he has had undetectable levels of plasma viremia, and HIV-1 cannot be isolated from him. Sequencing of proviral DNA indicates that the only HIV-1 sequences that can be identified in AD-18 have gross defects in the p17-encoding regions of the gag gene (Y. Huang, L. Zhang, and D. D. Ho, Virology 240:36–49, 1998). However, AD-18 has strong, sustained antibody responses to several HIV-1 antigens, including p17. Cytotoxic T-lymphocyte responses to Env and Gag antigens have gradually diminished over the past 4 years, at a time when the titers of antibodies to the same proteins have remained stable. We discuss what these observations might mean for the generation and maintenance of immunological memory.

scholarly journals Identification of new HIV-1 Gag-specific cytotoxic T lymphocyte responses in BALB/c mice

2008 ◽  
Vol 5 (1) ◽  
pp. 81 ◽  
Author(s):  
Silvia Cellini ◽  
Cinzia Fortini ◽  
Eleonora Gallerani ◽  
Federica Destro ◽  
Egidio Cofano ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Responses ◽  
Hiv 1
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