title: Broadly neutralizing antibodies developed by an HIV-positive elite neutralizer exact a replication fitness cost on the contemporaneous virus.
abstract: Approximately 1% of those infected with HIV-1 develop broad and potent serum cross-neutralizing antibody activities. It is unknown whether or not the development of such immune responses affects the replication of the contemporaneous autologous virus. Here, we defined a pathway of autologous viral escape from contemporaneous potent and broad serum neutralizing antibodies developed by an elite HIV-1-positive (HIV-1(+)) neutralizer. These antibodies potently neutralize diverse isolates from different clades and target primarily the CD4-binding site (CD4-BS) of the viral envelope glycoprotein. Viral escape required mutations in the viral envelope glycoprotein which limited the accessibility of the CD4-binding site to the autologous broadly neutralizing anti-CD4-BS antibodies but which allowed the virus to infect cells by utilizing CD4 receptors on their surface. The acquisition of neutralization resistance, however, resulted in reduced cell entry potential and slower viral replication kinetics. Our results indicate that in vivo escape from autologous broadly neutralizing antibodies exacts fitness costs to HIV-1.
authors.affiliation: Seattle BioMed, Seattle, Washington, USA.
authors.forename: D Noah
authors.initials: DN
authors.lastname: Sather
authors.forename: Sara
authors.initials: S
authors.lastname: Carbonetti
authors.forename: Jenny
authors.initials: J
authors.lastname: Kehayia
authors.forename: Zane
authors.initials: Z
authors.lastname: Kraft
authors.forename: Iliyana
authors.initials: I
authors.lastname: Mikell
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stamatatos
mesh_terms: D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D019302:HIV Envelope Protein gp160 / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D009500:Neutralization Tests; D053586:Virus Internalization; D014779:Virus Replication / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D017931:DNA Primers; D019302:HIV Envelope Protein gp160