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. 2014;10(2):512-8.
doi: 10.4161/hv.27125. Epub 2013 Nov 15.

VSports - Host genomic HIV restriction factors modulate the response to dendritic cell-based treatment against HIV-1

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Host genomic HIV restriction factors modulate the response to dendritic cell-based treatment against HIV-1

VSports在线直播 - Alessandra Pontillo et al. Hum Vaccin Immunother. 2014.

Abstract

Host genome is still poorly investigated in the context of vaccine or immunotherapy, however recently findings emphasized that it may affect the response to those treatments VSports手机版. In our retrospective study we evaluated the effect of HIV-1 genetic restriction factors on the response to dendritic cell (DC)-based immunotherapy in a Brazilian cohort of HIV positive (HIV+) patients that underwent a phase I clinical trial in 2004. Genomic DNA from 18 HIV+ individuals that underwent DC-based immunotherapy was analyzed for selected polymorphisms known to be associated with susceptibility to HIV-1 infection and/or AIDS progression. Allelic and genotypic distribution of the 22 polymorphisms was evaluated considering the response to the treatment. The rs11884476 SNP in PARD3B resulted associated with good response to immune treatment according to an over-dominant model. Even if functional effect of this variation is still unknown, our data suggested that it could play a role in the control of viral replication. Our findings, being aware of the limitation represented by the small number of subjects analyzed, suggest that genetic factors involved in AIDS progression could affect the response to immunotherapy, reinforcing the idea that deeper investigation on host genetic variations will be fundamental for a rational vaccine development. .

Keywords: DC-based immune-treatment; HIV vaccine; PARD3B; host genome and response to vaccine V体育安卓版. .

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Figures

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Figure 1. Plasma viral load (PVL) reduction and cellular response in 18 HIV+ patients who’s underwent DC-based immune treatment against HIV-1 according to PARD3B rs11884476 genotypes. Change in PVL expressed as log change (∆log), change in CD4+ and CD8+ cells counts (∆cells/µl) and change in percentage of CD4+ and CD8+ cells producing IFN-ϒ (∆%) are reported for the 18 HIV+ patients included in the phase I clinical trial of DC-based immune-therapy classified according to PARD3B rs11884476 genotypes. The data, obtained from Lu et al., represent difference (∆) between values presented 1 y after immunization and before the starting of the trial. Individual data and media were reported. (A) Plasma viral load (PVL). Individual blood CD4+ (B) and CD8+ (C) cell counts. (D and E) Intracellular IFN-γ detection of T cells following stimulation with HIV-1-pulsed DC. Percentage of total CD4+ (D) or CD8+ (E) cell secreting IFN-γ is reported. T test analysis was performed between C/C and C/G groups and between C/C+G/G and C/G groups according to an over-dominant model. Being unique value the G/G has been excluded from the analysis. *P < 0.05; **P < 0.01.
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Figure 2. Possible interactions between PARD3B and SMAD proteins influencing TGFß signaling. The two hypotheses concerning the dual role of PARD3 in terms of viral replication control or DC-mediated lymphocytes activation are reported according to rs11884476 genotypes (2A: wild type C/C genotype; 2B: G/G genotype). The up or downregulation of TGFß signaling and the consequences in terms of AIDS progression or DC immune-regulation are evidenced in red rectangles.

References

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