Immunologic and virologic studies in long-term nonprogressors with HIV-1 infection.
BACKGROUND
It is not known whether clinical latency in long-term nonprogressors (LTNP) with HIV-1 infection is due to a strong HIV-1 specific immune response of the host or to virologic factors. -


METHODS
Peripheral blood mononuclear cells (PBMC) of 6 LTNP were analyzed for their phenotype, proliferation rates, natural killer (NK) cell activity, antibody dependent cellular cytotoxicity (ADCC), and CCR5 chemokine receptor genotype. Furthermore sequence analyses of the HIV-1 gene were performed. -


RESULTS
Phenotypic analyses of lymphocyte subsets revealed increased CD8+ as well as HLA-DR+ expressing cells in LTNP and patients with progressive disease (PRO). Proliferation assays in LTNP and PRO showed a reduction of stimulation by polyclonal mitogens (PHA, ConA, PWM) of up to 60%. NK activity was within normal ranges in LTNP but reduced in PRO. 1 LTNP exhibited heterozygosity for CCR5-D32. A mutant HIV nef gene was not discovered by PCR in any of the LTNP. HIV-V3 loop PCR in 5 LTNP revealed the HIV-1B (NSI) subtype. In 2 patients further sequence analyses of the HIV-1 genome showed homozygous mutations in the Sp1 and NF-kB binding sites.


CONCLUSIONS
The non-progression of HIV-1 infection in some LTNP seems to be due to single mutations in the viral genome resulting in a less replicative HIV-1 subtype or to a mutant chemokine receptor leading to a reduced HIV-1 entry into CD4+ cells. NK cell activity might be an additional contributing factor in controlling viremia.
Mendila
M
M
Department of Medicine, Division of Clinical Immunology, Hannover Medical School, D-30625 Hannover, Germany. immunologie@mh-hannover. de.
Heiken
H
H
Becker
S
S
Stoll
M
M
Kemper
A
A
Jacobs
R
R
Schmidt
R E
RE
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D005260:Female; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019713:Receptors, CCR5 / Q000235:genetics
D019713:Receptors, CCR5