title: Emergence of autologous neutralization-resistant variants from preexisting human immunodeficiency virus (HIV) quasi species during virus rebound in HIV type 1-infected patients undergoing highly active antiretroviral therapy.
abstract: The role of neutralizing antibodies (NAbs) during virus rebound in human immunodeficiency virus type 1 (HIV-1)-infected patients undergoing highly active antiretroviral therapy is poorly understood. Three patients in this study had NAbs to preexisting autologous HIV-1 and an episode of virus rebound after a prolonged period of virus suppression. To investigate the influence of NAbs on virus evolution, envelope genotypes of preexisting and rebound viruses were examined. Phylogenetic analysis of env (V1-V5) sequences indicated that rebound viruses had evolved from or preexisted in baseline populations. By use of envelope pseudotype viruses, rebound viruses were found to be significantly resistant to neutralization by autologous antibody in all 3 patients, indicating that rebound viruses were selected by NAbs. The site responsible for conferring neutralization resistance against autologous antibody was identified in the upstream C3 region in 2 of 3 patients.
authors.affiliation: Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan. 993d9775@gsst.kumamoto-u.ac.jp
authors.forename: Feng-Xiang
authors.initials: FX
authors.lastname: Wang
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nishihara
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koito
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsushita
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D002460:Cell Line; D015752:Genes, env / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments