Effects of mutations on HIV-1 infectivity and neutralization involving the conserved NNNT amino acid sequence in the gp120 V3 loop.
The N-glycan g15 within the HIV-1 gp120 V3 loop efficiently blocks antibodies to facilitate viral escape from humoral immune responses. However, we have isolated primary viruses all lacking the N-glycosylation site g15 due to mutations (NNNT>YRNA, HNTV, SIQK), which showed resistance to neutralizing antibodies present in autologous or heterologous HIV-1 positive sera. When introduced into the NL4-3 background, the sequences YRNA, HNTV and SIQK caused an increase of viral infectivity and resistance to neutralization. Thus, despite the lack of g15, primary isolates can escape from neutralization because of specific mutations of the NNNT sequence altering coreceptor usage.
Polzer
Svenja
S
Bernhard Nocht Institute for Tropical Medicine, Department of Virology, Hamburg, Germany.
Müller
Harm
H
Schreiber
Michael
M
D020816:Amino Acid Motifs / Q000235:genetics; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D009154:Mutation
D000906:Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1