TY - JOUR
T1 - Changing sensitivity to broadly neutralizing antibodies b12, 2G12, 2F5, and 4E10 of primary subtype B human immunodeficiency virus type 1 variants in the natural course of infection
AU - Bunnik, Evelien M.
AU - van Gils, Marit J.
AU - Lobbrecht, Marilie S. D.
AU - Pisas, Linaida
AU - van Nuenen, Ad C.
AU - Schuitemaker, Hanneke
PY - 2009
Y1 - 2009
N2 - The conserved nature of the epitopes of the four broadly neutralizing antibodies (BNAbs), b12, 2G12, 2F5, and 4E10, may imply that the sensitivity of HIV-1 for these BNAbs remains fairly constant over the course of infection. Here, we demonstrate that viruses isolated early during the course of infection were mostly sensitive to HIVIg and antibody neutralization, although variation was observed in neutralization sensitivity of coexisting viruses to the different antibodies as well as between viruses from different patients. HIV-1 resistance to HIVIg developed relatively early during follow-up in three out of five patients, while early, b12 sensitive viruses in three out of five patients were replaced by b12 resistant variants relatively late in infection. In contrast, viruses generally remained sensitive to 2F5 and 4E10 neutralization over the Course of infection, although 2F5 and/or 4E10 resistant variants did emerge later in infection in four out of five patients. In most patients, HIV-1 resistance to 2F5 or 4E10 did not correlate with mutations at critical amino acid positions in their defined epitopes. Viruses resistant to 2G12-mediated neutralization were present throughout the course of infection. As viral resistance against BNAb-mediated neutralization generally developed when autologous serum neutralizing activity had faded, it seems unlikely that these changes are driven by escape from autologous humoral immunity. (C) 2009 Elsevier Inc. All rights reserved
AB - The conserved nature of the epitopes of the four broadly neutralizing antibodies (BNAbs), b12, 2G12, 2F5, and 4E10, may imply that the sensitivity of HIV-1 for these BNAbs remains fairly constant over the course of infection. Here, we demonstrate that viruses isolated early during the course of infection were mostly sensitive to HIVIg and antibody neutralization, although variation was observed in neutralization sensitivity of coexisting viruses to the different antibodies as well as between viruses from different patients. HIV-1 resistance to HIVIg developed relatively early during follow-up in three out of five patients, while early, b12 sensitive viruses in three out of five patients were replaced by b12 resistant variants relatively late in infection. In contrast, viruses generally remained sensitive to 2F5 and 4E10 neutralization over the Course of infection, although 2F5 and/or 4E10 resistant variants did emerge later in infection in four out of five patients. In most patients, HIV-1 resistance to 2F5 or 4E10 did not correlate with mutations at critical amino acid positions in their defined epitopes. Viruses resistant to 2G12-mediated neutralization were present throughout the course of infection. As viral resistance against BNAb-mediated neutralization generally developed when autologous serum neutralizing activity had faded, it seems unlikely that these changes are driven by escape from autologous humoral immunity. (C) 2009 Elsevier Inc. All rights reserved
U2 - https://doi.org/10.1016/j.virol.2009.05.028
DO - https://doi.org/10.1016/j.virol.2009.05.028
M3 - Article
C2 - 19539340
SN - 0042-6822
VL - 390
SP - 348
EP - 355
JO - Virology
JF - Virology
IS - 2
ER -