title: A possible origin of emerged HIV-1 after interrupting anti-retroviral therapy.
abstract: Although HIV-1 can be successfully eradicated from the circulating blood of HIV-1-infected individuals using anti-retroviral therapy (ART), HIV-1 virions emerge immediately after the interruption of ART. This study was aimed to investigate the origin of the emerged HIV-1. After obtaining informed consent, blood samples from nine HIV-1-infected individuals and endoscopic ileum samples from five of the individuals were obtained. Purified peripheral mononuclear cells (PBMCs)and ileum cells were analyzed by flow-cytometry, and the V3 loop sequences of the HIV-1 envelope protein were determined. By comparing the V3 loop sequences of the samples, we confirmed that the provirus hidden in the CD4(+) PBMCs was not the source of the HIV-1 that emerged after the interruption of ART. Although free virus and HIV-1-p24 antigen (p24)-positive cells were not seen in the blood of patients receiving ART, proviral DNA and p24 could be detected in the ileum from the same patient. Among the HIV-1-infected CD4(+) cells in the ileum samples, Vα24(+) natural killer T (NKT) cells were the major p24-positive cells. These results suggest that the innate NKTcells in the mucosal compartment are the most likely candidates for the origin of the HIV-1 that emerged after ART was interrupted.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Matsumura
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Kyoko
authors.initials: K
authors.lastname: Omi
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Nagata
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinya
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments