title: Detection of HIV-1 matrix protein p17 quasispecies variants in plasma of chronic HIV-1-infected patients by ultra-deep pyrosequencing.
abstract: BACKGROUND
  The HIV-1 matrix protein p17 (p17MA) is a pleiotropic protein that plays a key role in the HIV-1 life cycle. It has been long believed to have a highly conserved primary amino acid sequence and a well-preserved structural integrity to avoid severe fitness consequences. However, recent data revealed that the carboxy (COOH)-terminus of p17MA possesses high levels of predicted intrinsic disorder, which would subtend to at least partially unfolded status of this region. This finding pointed to the need of investigating p17MA heterogeneity.
  
  
  METHODS
  The degree of intrapatient variations in the p17MA primary sequence was assessed on plasma viral RNA by using ultra-deep pyrosequencing.
  
  
  RESULTS
  Data obtained support a complex nature of p17MA quasispecies, with variants present at variable frequency virtually in all patients. Clusters of mutations were scattered along the entire sequence of the viral protein, but they were more frequently detected within the COOH-terminal region of p17MA. Moreover, deletions and insertions also occurred in a restricted area of the COOH-terminal region.
  
  
  CONCLUSIONS
  On the whole, our data show that the intrapatient level of sequence diversity in the p17MA is much higher than predicted before. Our results pave the way for further studies aimed at unraveling possible correlations between the presence of distinct p17MA variants and peculiar clinical evolutions of HIV-1 disease. The presence of p17MA quasispecies diversity may offer new tools to improve our understanding of the viral adaptation during the natural history of HIV-1 infection.
authors.affiliation: *National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy; †Cancer Bio-Immunotherapy Unit, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano (PN), Italy; and ‡Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giombini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Caccuri
authors.forename: Marina
authors.initials: M
authors.lastname: Selleri
authors.forename: Gabriella
authors.initials: G
authors.lastname: Rozera
authors.forename: Isabella
authors.initials: I
authors.lastname: Abbate
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartolini
authors.forename: Debora
authors.initials: D
authors.lastname: Martorelli
authors.forename: Damiana Antonia
authors.initials: DA
authors.lastname: Faè
authors.forename: Simona
authors.initials: S
authors.lastname: Fiorentini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giagulli
authors.forename: Maria R
authors.initials: MR
authors.lastname: Capobianchi
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D015488:HIV Antigens; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1