Amino Acid Sequence ; Blood Donors ; Gene Deletion ; Gene Products, nef ; chemistry ; genetics ; Humans ; Molecular Sequence Data ; nef Gene Products, Human Immunodeficiency Virus

BACKGROUNDThe correlation between HIV-1 Nef-specific CD8 T-cell responses and markers of HIV-1 disease progression still remains unclear. This study analysed and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with different disease status.

METHODSTwo groups of patients with HIV-1 subtype B infection were selected according to CD4 count and clinical manifestations: long-term nonprogressors (LTNPs, n = 20) and advanced progressors (APs, CD4 count < 500 cells/microl, n = 34). Nef-specific CD8 T-cell responses were studied by interferon-gamma ELISpot assay against 3 pools of HIV-Nef peptides.

RESULTSNef-specific CD8 T-cell responses did not correlate with viral load or CD4 count in all patients and no significant differences were found in the magnitude of Nef-specific CD8 T-cell responses between groups LTNPs and APs (670 SFC/10(6) peripheral blood mononuclear cells vs 1107 SFC/10(6) peripheral blood mononuclear cells, P = 0.255). Further comparisons showed that there were also no significant correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated negatively with viral load (r = -0.397, P = 0.020) and positively with CD4 count (r = 0.364, P = 0.034) in group APs.

CONCLUSIONThese data suggest that different correlation patterns between Nef-specific CD8 T-cell responses and disease progression exist in LTNPs and APs. Although a negative association was observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses might fail to play a protective role in different stages of HIV-1 infection.

Acquired Immunodeficiency Syndrome ; immunology ; Adult ; CD4 Lymphocyte Count ; CD8-Positive T-Lymphocytes ; immunology ; Disease Progression ; Female ; Gene Products, nef ; immunology ; HIV-1 ; classification ; Humans ; Male ; Middle Aged ; RNA, Viral ; blood ; nef Gene Products, Human Immunodeficiency Virus

OBJECTIVETo study the genetic diversity of HIV-1 nef genes from a patient with AIDS dementia complex(ADC) , so as to research the amino acid variability and the pathogenesis of ADC.

METHODSThe nef gene was amplified with PCR from genomic DNA which was extracted from spleen and different brain tissues(basal ganglia, frontal gray matter, meninges, temporal lobe)of a patient who died of ADC. PCR products were cloned into the pMD19-T vector, after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced and confirmed with BLAST. HIV-1 nef sequences were processed with BioEdit and MEGA4 to do Neighbor-Joining tree, p-Distances, and values of ds/dn.

RESULTSThe samples were all identified as HIV-1 B and genetic variation exists in HIV-1 nef gene isolated from different tissues compared with HXB2. In addition,part of the changes were different between periphery and brain.

CONCLUSIONVariations exist in the HIV-1 nef gene extracted from the ADC patient and the variations from peripheral and central nerve tissues were different,these variations may change the function of Nef,and it needs more research.

AIDS Dementia Complex ; virology ; Adult ; DNA, Viral ; genetics ; Genetic Variation ; HIV Infections ; virology ; HIV-1 ; genetics ; Humans ; Male ; nef Gene Products, Human Immunodeficiency Virus ; genetics