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

作者：Giombini Emanuela; Dolcetti Riccardo; Caccuri Francesca; Selleri Marina; Rozera Gabriella; Abbate Isabella; Bartolini Barbara; Martorelli Debora; Fae Damiana Antonia; Fiorentini Simona; Giagulli Cinzia; Capobianchi Maria R; Caruso Arnaldo^*

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2014, 66(3): 332-339.

DOI：10.1097/QAI.0000000000000164

• HIV-1
• matrix protein p17
• COOH-terminal region
• quasispecies
• amino acid diversity

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.

• 出版日期2014-7-1