title: Influence of HAART on alternative reading frame immune responses over the course of HIV-1 infection.
abstract: BACKGROUND
  Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo.
  
  
  RESULTS
  In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased.
  
  
  CONCLUSIONS
  These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.
authors: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors: Stephane
authors: S
authors: Champiat
authors: Rui André Saraiva
authors: RA
authors: Raposo
authors: Nicholas J
authors: NJ
authors: Maness
authors: John L
authors: JL
authors: Lehman
authors: Sean E
authors: SE
authors: Purtell
authors: Aaron M
authors: AM
authors: Hasenkrug
authors: Jacob C
authors: JC
authors: Miller
authors: Hansi
authors: H
authors: Dean
authors: Wayne C
authors: WC
authors: Koff
authors: Marisa Ailin
authors: MA
authors: Hong
authors: Jeffrey N
authors: JN
authors: Martin
authors: Steven G
authors: SG
authors: Deeks
authors: Gerald E
authors: GE
authors: Spotts
authors: Christopher D
authors: CD
authors: Pilcher
authors: Fredrick M
authors: FM
authors: Hecht
authors: Esper G
authors: EG
authors: Kallas
authors: Keith E
authors: KE
authors: Garrison
authors: Douglas F
authors: DF
authors: Nixon
mesh_terms: D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D002908:Chronic Disease; D018450:Disease Progression; D016679:Genome, Viral / Q000235:genetics; D005843:Geography; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016364:Reading Frames / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic / Q000235:genetics; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics
chemical_list: D009711:Nucleotides; D010455:Peptides; D054299:env Gene Products, Human Immunodeficiency Virus