Research Group Heussler (Malaria I) - Bernhard-Nocht-Institut für ...

CXCR4 expressing cells. Thus, these cells are the first
targets for viruses developing CXCR4-specificity in addition
to CCR5. In late stage of infection, when neutralizing
antibody activity in human serum is low, gp120
mutants emerge lacking g15. These viruses show higher
replication rates on CXCR4 cells compared to the
glycosylated R5X4 or X4 viruses.
The data demonstrate that N-glycans on gp120 and
CXCR4 play an important role for the development of
the viral quasispecies in patients.
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Selected Publications
• Polzer, S.;Dittmar, M. T.;Schmitz, H. and Schreiber,
M. (2002). The N-linked glycan g15 within the V3 loop
of the HIV-1 external glycoprotein gp120 affects coreceptor
usage, cellular tropism, and neutralization. Virology
304: 70-80.
• Thordsen, I.;Polzer, S. and Schreiber, M. (2002). Infection
of cells expressing CXCR4 mutants lacking Nglycosylation
at the N-terminal extracellular domain is
enhanced for R5X4-dualtropic human immunodeficiency
virus type-1. BMC Infect Dis 2: 31.
Investigators
• Michael Schreiber
• Svenja Polzer
• Ingo Thordsen,
• Herbert Schmitz
Medical Microbiology Section
Figure 2: Complex carbohydrates involved in the interaction of gp120 and the CXCR4 coreceptor.
The HIV-1 envelope of NL4-3 virus contains 24 sites for N-glycosylation. Five of these sites g13-g17 are
located next to the V3 loop. The gp120 V3 loop is a hypervariable region, which binds to the CXCR4
coreceptor. The N-glycan g15, located within the V3 loop, was found to play the major role for masking
the V3 loop. The g15 N glycan is blocking neutralizing antibodies, which is important for HIV-1 in
the early stage of infection. On CXCR4 two complex carbohydrate structures g1 and g2 are present.
The N-glycan g1 within the N-terminal region of CXCR4 plays a role in the entry process of HIV-1 also.
Cells expressing a CXCR4 mutant lacking the g1 N-glycan showed higher permissiveness for R5X4 dualtropic
viruses.