Project description:To identify functional lncRNAs in microglia-neurotropic virus interaction, high-throughput RNA sequencing was performed to obtain differential expressed lncRNAs (DELs) in microglia isolated from C57BL/6J mice, infected with or without neurotropic virus herpes simplex virus type 1 (HSV-1) (MOI 1 per group). All samples contain three mice’s microglia as a mixture given the isolated amount is low.
Project description:Acute influenza infection can be associated with neurological symptoms. Especially after the major pandemics reports about neuropsychiatric complications accumulated. However, the long-term consequences for the CNS of an infection with neurotropic but also non-neurotropic influenza A virus (IAV) variants remain largely elusive. The results presented here show that synapse loss in the hippocampus upon an infection with neurotropic H7N7 (rSC35M) as well as non-neurotropic H3N2 (maHK68) persists well beyond the acute phase of the disease. While hippocampal synapse number was significantly reduced 30 days post infection with both H7N7 and H3N2, full recovery could be observed 120 days post infection. Notably, infection with H1N1 (PR8) which was shown previously to affect spine number and hippocampus-dependent learning during the acute phase had no significant long-term effects. Spine loss was associated with an increase in the number of activated microglia, reduced long-term potentiation and an impairment in spatial memory formation in the water maze indicating long-term inflammation induced functional and structural alterations in the hippocampus. Our data, therefore, provide evidence that while neuroinflammation induced by neurotropic H7N7 showed the strongest effect, also the systemic infection with a non-neurotropic influenza virus can result in long-term impairments in synapse number and function in the hippocampus. While young animals fully recover the outcome might be different in aged or otherwise compromised individuals, thereby directing future treatment strategies to pay attention to IAV induced processes of neuroinflammation.
Project description:Neurotropic viral infections of the central nervous system (CNS) cause a broad spectrum of clinical manifestations, which include neuropathological changes and subsequent neurological conditions. Currently utilized antiviral drugs are targeted towards specific viruses or members of a specific family. However, the recent COVID-19 pandemic caused by the neurotropic virus SARS-CoV-2 has highlighted the importance of having broad spectrum agents available in our armamentarium that can limit replication of emerging and reemerging neurotropic viruses and future unidentified pathogens that can pose a risk for the next pandemic. Neural progenitor cells (NPCs) were derived from hiPSC-neurons as previously described (D’Aiuto et al. Organogenesis. 2014;10(4):365-77).
Project description:Goal: Determine the role of microglia in the antiviral response during neurotropic picornavirus infection of C57BL/6J and SJL/J mice and whether absence of microglia would affect CD4 and CD8 T cell functions. Methods: Brains from C57BL/6J and SJL/J mice treated with PLX5622 (to deplete microlgia) or control diet were harvested at 6 days post TMEV-infection. CD4+ T cells and CD8+ T cells were obtained using Easy Sep Mouse CD4+ T cell isolation Kit and Easy Sep Mouse CD8+ T cell isolation Kit (Stemcell). RNA was obtained using RNeasy (QIAGEN) and Illumina TruSeq stranded RNA Kit with Ribo-Zero Gold was then utilized to prepare cDNA library for RNA-seq. Results: Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.
Project description:We used the high-throughput sequencing and inhibitors to screen microRNAs that play the role in anti-porcine reproductive and respiratory syndrome virus (PRRSV) responses in porcine alveolar macrophages (PAMs).
Project description:The pig is important for agriculture and as an animal model in human and veterinary medicine, yet, despite over 20 years of effort, it has proved a difficult species from which to generate pluripotent stem cells analogous to those derived from mouse embryos. Here we report the production of LIF-dependent, so called naïve type, pluripotent stem cells from the inner cell mass of porcine blastocysts by up-regulating expression of KLF4 and POU5F1. These cells resemble mouse ES cells and are distinct from the FGF2-dependent, induced pluripotent cell type derived from porcine somatic cells. High throughput SNP chip genotyping was conducted on Illumina's Porcine SNP60 BeadChip (WG-410, a service provided by Geneseek, NE, http://www.neogen.com/GeneSeek/). The results exhibited that the two lines pluripotent stem cells from the inner cell mass of porcine blastocysts were porcine origin and genetically distinct.
Project description:We performed small RNA-seq on Dicer KD and control porcine oocyte, and report endo-siRNAs corresponding to SINE1B are significantly down-regulated by Dicer knockdown and are essential for in vitro maturation of porcine oocyte