title: Human immunodeficiency virus type 1 evasion of a neutralizing anti-V3 antibody involves acquisition of a potential glycosylation site in V2.
abstract: It has been reported that the addition of a potential N-linked glycosylation site (PNGS) to the gp120 human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein provides protection against neutralizing antibodies (NAbs) by acting as a 'glycan shield'. In this study, we induced insertion of a PNGS into the V2 region of HIV-1(BaL) with the KD-247 anti-V3 neutralizing monoclonal antibody. In the presence of KD-247 (200 microg ml(-1)) at passage five, viruses with 3 aa mutations in the C2 (T240S and I283T) and V3 (T319A) regions expanded from pre-existing variants. After six passages with KD-247 (>300 microg ml(-1)), a PNGS emerged in the V2 region in addition to C2 (T240S) and V3 mutations (R315K and F317L). A variant with a PNGS insertion in V2, but no V3 mutations was sensitive to KD-247, whereas a clone with a V2 PNGS insertion and mutations in V3 demonstrated a high level of resistance to KD-247. Replication kinetic analysis revealed that the F317L mutation in V3 played a compensatory role for fitness-loss caused by the PNGS insertion in V2. The evading HIV-1 variant did not revert back to the wild-type virus after 14 passages without KD-247. These findings demonstrate that the virus with fitness-loss mutations can replicate equally as well as the wild-type virus to acquire some key mutations in the V3 stem and the C2 region, and the compensated variants containing PNGS do not revert back to the ancestral virus even in the absence of NAb.
authors.affiliation: Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Hatada
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Harada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kawanami
authors.forename: Junji
authors.initials: J
authors.lastname: Shibata
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsushita
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D057134:Antibodies, Neutralizing / Q000276:immunology*; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral