ABSTRACT
Although 2-long terminal repeat (2-LTR) circles are only a fraction of the total viral DNA in infected cells, sequence analysis of 2-LTR circles reveals critical information regarding viral DNA synthesis and the nature of actively replicating virus. It was observed that a large proportion of the 2-LTR circular molecules in the peripheral blood mononuclear cell (PBMC) DNA of infected individuals are mutated at the circle junction. The integrase inhibitor raltegravir (RAL) blocks the strand transfer step of the integration of HIV-1; as a consequence of abortive integration a significant increase of episomal 2-LTR circles is observed. Moreover, it was demonstrated that in patients treated with highly active retroviral therapy (HAART) changes in 2-LTR concentration did not affect junction sequences and flanking regions of 2-LTR. Here we evaluated whether RAL therapy could have a differential impact on the 2-LTR circle junctional sequences in patients with different virological profiles at the time of starting RAL therapy. Sequence analysis indicates that RAL acts differently in the two populations.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV Long Terminal Repeat/drug effects , HIV-1/drug effects , Pyrrolidinones/therapeutic use , Adult , Female , HIV-1/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Raltegravir Potassium , Sequence Analysis, DNAABSTRACT
INTRODUCTION: The development of new strategies for the induction of potent and broad immune responses is of high priority in the vaccine field. In this setting, integrase-defective lentiviral vectors (IDLV) represent a new and promising delivery system for immunization purposes. AREAS COVERED: In this review we describe the development and application of IDLV for vaccination. IDLV are turning out to be a new class of vectors endowed with peculiar characteristics, setting them apart from the parental integration-competent lentiviral vectors. Recent data suggest that IDLV are able to induce strong antigen-specific immune responses in terms of quantity, persistence and quality of CD8(+) T cell response following a single immunization in mice. EXPERT OPINION: IDLV are a recent acquisition in the field of genetic immunization, thus allowing for the opportunity of further upgrading, including increasing antigen expression and potency of immune response. Based on recent reports showing the potential of IDLV for immunization in mouse models, further development and validation of IDLV, including comparison with other vaccine protocols and use in non-human primate models, are warranted.
