Skip Navigation LinksHome > July 1, 2014 - Volume 66 - Issue 3 > Detection of HIV-1 Matrix Protein p17 Quasispecies Variants...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000164
Epidemiology and Prevention

Detection of HIV-1 Matrix Protein p17 Quasispecies Variants in Plasma of Chronic HIV-1–Infected Patients by Ultra-Deep Pyrosequencing

Giombini, Emanuela PhD*; Dolcetti, Riccardo MD; Caccuri, Francesca PhD; Selleri, Marina PhD*; Rozera, Gabriella PhD*; Abbate, Isabella PhD*; Bartolini, Barbara PhD*; Martorelli, Debora PhD; Faè, Damiana Antonia PhD; Fiorentini, Simona PhD; Giagulli, Cinzia PhD; Capobianchi, Maria R. PhD*; Caruso, Arnaldo MD

Supplemental Author Material
Collapse Box

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.

© 2014 by Lippincott Williams & Wilkins

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.