250-T. Clinical Relevance of Tandem-Repeat Polymorphisms in the Genetic Sequence of L-SIGN, a Novel HIV-Transreceptor

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Session 44 Poster Session
DC-SIGN and Dendritic Cells
Session Time: 4:30-6:30 pm
Room 4E-F

250-T.

Clinical Relevance of Tandem-Repeat Polymorphisms in the Genetic Sequence of L-SIGN, a Novel HIV-Transreceptor
M. Lichterfeld*, H. D. Nischalke, J. Söhne, N. Quirishi, T. Sauerbruch, U. Spengler, and J. K. Rockstroh
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/µL 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.