By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Fresh data on Oncology are presented in a new report. According to news originating from Chapel Hill, North Carolina, by NewsRx correspondents, research stated, "Tripartite motif proteins are important viral restriction factors and affect processes ranging from uncoating to transcription to immune signaling. Specifically, the promyelocytic leukemia protein (TRIM19; also called PML) is a viral restriction factor inhibiting processes from uncoating to transcription to cell survival."
Our news journalists obtained a quote from the research from the University of North Carolina, "Here we investigated PML's effect on adeno-associated virus (AAV), a parvovirus used for gene delivery. Although dependovirus (AAV) and autonomous parvovirus (minute virus of mice) replication centers can colocalize with PML, PML's functional effect on parvoviruses is unknown. Using PML knockout mice, we determined that PML knockout enhances recombinant AAV2 (rAAV2) transduction at a range of vector doses in both male and female mice. In fact, male and female PML knockout mice exhibited up to 56-fold and 28-fold increases in transduction, respectively. PML inhibited several rAAV serotypes, suggesting a conserved mechanism, and organ specificity correlated with PML expression. Mechanistically, PML inhibited rAAV second-strand DNA synthesis, precluding inhibition of self-complementary rAAV, and did not affect the prior steps in transduction. Furthermore, we confirmed the effect of human PML on rAAV transduction through small interfering RNA (siRNA)-mediated knockdown in HuH7 cells and determined that the highest level of inhibition was due to effects of PML isoform II (PMLII). Overexpression of PMLII resulted in inhibition of second-strand synthesis, vector production, and genome replication. Moreover, wild-type AAV2 production and infectivity were also inhibited by PMLII, demonstrating a PML interaction with wild-type AAV. These data have important implications for AAV-mediated gene therapy."
According to the news editors, the research concluded: "Additionally, PMLII inhibition of AAV second-strand synthesis and replication, which are processes necessary for all parvoviruses, suggests implications for replication of other parvoviruses."
For more information on this research see: Promyelocytic Leukemia Protein Is a Cell-Intrinsic Factor Inhibiting Parvovirus DNA Replication. Journal of Virology, 2014;88(2):925-936. Journal of Virology can be contacted at: Amer Soc Microbiology, 1752 N St NW, Washington, DC 20036-2904, USA. (American Society for Microbiology - www.asm.org; Journal of Virology - jvi.asm.org)
The news correspondents report that additional information may be obtained from A.M. Mitchell, University of North Carolina, Dept. of Pharmacol, Chapel Hill, NC, United States. Additional authors for this research include M.L. Hirsch, C.W. Li and R.J. Samulski (see also Oncology).
Keywords for this news article include: Biotechnology, Genetics, Oncology, Viral DNA, Hematology, Chapel Hill, DNA Research, Mucoproteins, United States, North Carolina, Bioengineering, DNA Replication, Medical Devices, Intrinsic Factor, Leukemia Gene Therapy, Promyelocytic Leukemia, North and Central America
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