Lichterfeld M, Nischalke HD, Sohne J, Quirishi N, Sauerbruch T, Spengler U, Rockstroh JK; Conference on Retroviruses and Opportunistic Infections.
9th Conf Retrovir Oppor Infect Feb 24 28 2002 Wash State Conv Trade Cent Seattle Wash Conf Retrovir Oppor Infect 9th 2002 Seattle Wash. 2002 Feb 24-28; 9: abstract no. 250-T.
Univ. of Bonn, Germany
BACKGROUND: L-SIGN, a cell-surface C-type lectin primarily expressed on lymph node epithelium has recently been identified as a transreceptor for HIV that binds the HIV with high affinity and can increase virus transmission to HIV target cells. The extracellular domain of this molecule comprises several 23-residue tandem repeats whose number varies interindividually, ranging from 3-9. The variable number of repeats could possibly affect functional characteristics of the L-SIGN molecule and might alter HIV binding properties. In the present study, we determined the distribution of the various L-SIGN-associated tandem repeat allels in HIV patients and analyzed their potential impact for the clinical progression of HIV infection.METHODS: The L-SIGN genotype of 391 HIV patients was determined. Within these patients, 57 individuals were characterized as long-term non-progressors (no AIDS-defining event, CD4 cell count > 450/micro-L and HIV-RNA < 10.000 for a minimum of 5 years, no antiretroviral treatment exposure). 51 patients who had an AIDS-defining event at the time of initial HIV-infection were considered as rapid progressors. 134 healthy subjects served as a control group. Gene analysis was based on PCR-mediated amplification of the polymorphic gene sequence.RESULTS: Allele distribution was fairly similar in HIV patients and healthy subjects (3 repeats: 0.1% vs. 0%, 4 repeats: 3% vs 3.4%, 5 repeats: 27.5% vs 28.6%, 7 repeats: 50.7% vs 53%, 8 repeats: 0.4% vs 0%, 9 repeats: 2.1% vs 1.9%). L-SIGN allels containing 6 tandem repeats were slighlty more frequent in HIV patients as compared to healthy individuals (16.2% vs 13.2%, p>0.1). This difference reached statistical significance when HIV patients with a rapid clinical progression were compared to healthy controls (18.6% vs 13.2%, p<0.05). The frequency of 6-repeat containing allels in long-term non-progressing patients was 14.8%. Moreover, among rapidly progressing HIV patients, relative CD4 cell counts were significantly lower in patients with at least 1 6-repeat containg L-SIGN allel (7% vs 12.6%, p<0.05).CONCLUSIONS: 6-repeat containing alleles of the L-SIGN gene may be associated with a faster HIV disease progression and lower CD4 cell count.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Alleles
- Base Sequence
- CD4 Lymphocyte Count
- Disease Progression
- Genotype
- HIV Infections
- HIV Seropositivity
- Humans
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Tandem Repeat Sequences
- genetics
Other ID:
UI: 102263625
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