TY  - JOUR
A1  - Rowinska, Zuzanna
A1  - Gorressen, Simone
A1  - Merx, Marc W.
A1  - Koeppel, Thomas A.
A1  - Liehn, Elisa A.
A1  - Zernecke, Alma
T1  - Establishment of a New Murine Elastase-Induced Aneurysm Model Combined with Transplantation
JF  - PLOS ONE
N2  - Introduction: The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation. 
Methods: Adult male mice (n = 6-9 per group) underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting. 
Results: Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11 +/- 0.10 mm vs. 0.75 +/- 0.03 mm; p <= 0.001). Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts. 
Conclusions: We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals.
KW  - abdominal aortic-aneurysm
KW  - mouse models
KW  - prediction
KW  - dilation
KW  - rupture
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115774
SN  - 1932-6203
VL  - 9
IS  - 7
ER  - 
TY  - JOUR
A1  - Kincaid, Rodney P.
A1  - Chen, Yating
A1  - Cox, Jennifer E.
A1  - Rethwilm, Axel
A1  - Sullivan, Christopher S.
T1  - Noncanonical MicroRNA (miRNA) Biogenesis Gives Rise to Retroviral Mimics of Lymphoproliferative and Immunosuppressive Host miRNAs
JF  - mBio
N2  - MicroRNAs (miRNAs) play regulatory roles in diverse processes in both eukaryotic hosts and their viruses, yet fundamental questions remain about which viruses code for miRNAs and the functions that they serve. Simian foamy viruses (SFVs) of Old World monkeys and apes can zoonotically infect humans and, by ill-defined mechanisms, take up lifelong infections in their hosts. Here, we report that SFVs encode multiple miRNAs via a noncanonical mode of biogenesis. The primary SFV miRNA transcripts (pri-miRNAs) are transcribed by RNA polymerase III (RNAP III) and take multiple forms, including some that are cleaved by Drosha. However, these miRNAs are generated in a context-dependent fashion, as longer RNAP II transcripts spanning this region are resistant to Drosha cleavage. This suggests that the virus may avoid any fitness penalty that could be associated with viral genome/transcript cleavage. Two SFV miRNAs share sequence similarity and functionality with notable host miRNAs, the lymphoproliferative miRNA miR-155 and the innate immunity suppressor miR-132. These results have important implications regarding foamy virus biology, viral miRNAs, and the development of retroviral-based vectors. IMPORTANCE Fundamental questions remain about which viruses encode miRNAs and their associated functions. Currently, few natural viruses with RNA genomes have been reported to encode miRNAs. Simian foamy viruses are retroviruses that are prevalent in nonhuman host populations, and some can zoonotically infect humans who hunt primates or work as animal caretakers. We identify a cluster of miRNAs encoded by SFV. Characterization of these miRNAs reveals evolutionarily conserved, unconventional mechanisms to generate small RNAs. Several SFV miRNAs share sequence similarity and functionality with host miRNAs, including the oncogenic miRNA miR-155 and innate immunity suppressor miR-132. Strikingly, unrelated herpesviruses also tap into one or both of these same regulatory pathways, implying relevance to a broad range of viruses. These findings provide new insights with respect to foamy virus biology and vectorology.
KW  - MIR-155
KW  - simian foamy viruses
KW  - long terminal repeat
KW  - viral microRNAs
KW  - RNA
KW  - infection
KW  - herpesvirus
KW  - recognition
KW  - prediction
KW  - ortholog
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117216
SN  - 2150-7511
VL  - 5
IS  - 2
ER  -