title: Changes in host cell molecules acquired by circulating HIV-1 in patients treated with highly active antiretroviral therapy and interleukin-2.
abstract: OBJECTIVE
  To analyse cell membrane proteins (CMP) acquired by HIV-1 present in the plasma of asymptomatic patients, and their modifications after a cycle of highly active antiretroviral therapy (HAART) and interleukin (IL)-2.
  
  
  METHODS
  Plasma samples from eight drug-naive asymptomatic subjects underwent immobilized antibody capture (IAC) to detect CMP on the surface of circulating HIV-1. The CMP considered were lymphocyte subset markers (CD45RA, CD45RO), activation markers (HLA-DR), adhesion molecules (LFA-3), costimulatory proteins (B7-2), lymph-node homing receptors (CD62L) and pro-apoptosis molecules (FasL). This analysis was repeated after one cycle of HAART + IL-2, after virus rebound.
  
  
  RESULTS
  LFA-3, followed by CD45RO and HLA-DR, are the most represented CMP on the surface of circulating virions in naive asymptomatic patients; CD45RA, CD62L, B7-2 and FasL are detected only occasionally. After rebound, a significant reduction of CD45RO and HLA-DR, but not of LFA-3, is observed on virions, whereas CD45RA and CD62L, as well as other molecules, are not affected, remaining almost undetectable.
  
  
  CONCLUSIONS
  Assuming that CMP on HIV-1 reflect the cellular origin of virions, activated T cells expressing CD45RO, HLA-DR, and LFA-3 may be the main source of HIV-1 in asymptomatic patients. After a cycle of HAART + IL-2, followed by therapy interruption, CD45RA and CD62L are detected on virions rarely, indicating that even during virus rebound, expanded naive T cells do not become a major target of virus replication. Furthermore, the presence of HLA-DR on rebound HIV-1 is decreased, consistent with decreased activation of the HIV-producing cells. More extensive investigation may clarify the significance of these findings with respect to pathogenesis.
authors.affiliation: Laboratory of Microbiology, Sandro Pertini Hospital, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Abbate
authors.forename: F
authors.initials: F
authors.lastname: Dianzani
authors.forename: O
authors.initials: O
authors.lastname: Turriziani
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
authors.forename: G
authors.initials: G
authors.lastname: D'Offizi
authors.forename: V
authors.initials: V
authors.lastname: Galati
authors.forename: M
authors.initials: M
authors.lastname: Pierdominici
authors.forename: F
authors.initials: F
authors.lastname: Pandolfi
authors.forename: M R
authors.initials: MR
authors.lastname: Capobianchi
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D051940:B7-2 Antigen; D018791:CD4 Lymphocyte Count; D018968:CD58 Antigens / Q000378:metabolism; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D019041:L-Selectin / Q000378:metabolism; D019259:Lamivudine / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D014766:Viremia; D014771:Virion / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D051940:B7-2 Antigen; D018968:CD58 Antigens; C497964:CD86 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017320:HIV Protease Inhibitors; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018894:Reverse Transcriptase Inhibitors; D019041:L-Selectin; D019259:Lamivudine; D019469:Indinavir; D018119:Stavudine; D017493:Leukocyte Common Antigens