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Probability of N332 glycan occupancy on HIV-1 gp120 modulates sensitivity to broadly neutralizing antibodies.

Probability of N332 glycan occupancy on HIV-1 gp120 modulates sensitivity to broadly neutralizing antibodies.
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van den Kerkhof TL, van Gils MJ, Boeser-Nunnink BD, Burger JA, Schuitemaker H, Sanders RW,


van den Kerkhof TL, van Gils MJ, Boeser-Nunnink BD, Burger JA, Schuitemaker H, Sanders RW, (click to view)

van den Kerkhof TL, van Gils MJ, Boeser-Nunnink BD, Burger JA, Schuitemaker H, Sanders RW,

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AIDS (London, England) 30(14) 2179-84 doi 10.1097/QAD.0000000000001177

Abstract
OBJECTIVE(S)
The glycan shield of the HIV-1 envelope glycoprotein complex (Env), in particular the glycan at position 332 in gp120, is frequently targeted by broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals. We investigated the role of the second amino acid position of the N332 glycosylation motif Asn-X-Ser in HIV-1 evolution and neutralization sensitivity.

DESIGN AND METHODS
Viral variants harbouring glycosylation motifs with different probabilities of glycan occupancy were tested for their sensitivity to a subset of N332-dependent bNAbs. Furthermore, longitudinal Env sequences of 37 HIV-1 infected individuals were used to analyse the evolution of the N332 glycosylation motif within these individuals. Finally, early Env sequences from 31 historical and 21 contemporaneous seroconverters were compared to analyse this evolution on a population level.

RESULTS
Viral variants with a higher probability of N332 occupancy were more sensitive to neutralization by some N332-dependent bNAbs. Furthermore, the longitudinal analyses revealed an increase in probability of glycan occupancy of the N332 site over time, both within patients, and at the population level over the course of 20 years of HIV-1 epidemic.

CONCLUSIONS
These observations suggest that modulation of N332 glycan occupancy by the second amino acid position of the canonical glycosylation motif Asn-X-Ser plays a previously unappreciated role in viral escape from immune responses, and should be considered in Env-based vaccine design.

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