Chauhan, S. S. | Search bioRxiv

bioRxiv2020

Complete genome and phylogenetic analysis of bovine papillomavirus type 15 in Southern Xinjiang dairy cow

In this study, the complete genome sequence of bovine papillomavirus (BPV) type 15 (BPV Aks-02), a novel putative BPV type from a skin sample of a cow in southern Xinjiang, China was determined by collecting cutaneous neoplastic lesion, followed by DNA extraction and amplicon sequencing. The complete genome consisted of 7189 base pairs (G+C content of 42.50%) that encoded five early (E8, E7, E1, E2, E4) and two late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX2C zinc-binding domain and an LxCxE motif. The nucleotide sequence of the L1 open reading frame (ORF) was related mostly (99%) to the L1 ORF of putative type BAPV-3 reference strain from GenBank. Phylogenetic analysis and sequence similarities based on the L1 ORF suggest that BPV type (BPV Aks-02) clustered with members of genus Xipapillomavirus as BPV15, and closely related to Xipapillomavirus 1.

microbiology↗

bioRxiv2019

PIM Kinases Alter Mitochondrial Dynamics and Chemosensitivity in Lung Cancer

Resistance to chemotherapy represents a major obstacle to the successful treatment of non-small cell lung cancer (NSCLC). The goal of this study was to determine how PIM kinases impact mitochondrial dynamics, ROS production, and response to chemotherapy in lung cancer. Live cell imaging and microscopy were used to determine the effect of PIM loss or inhibition on mitochondrial phenotype and ROS. Inhibition of PIM kinases caused excessive mitochondrial fission and significant upregulation of mitochondrial superoxide, increasing intercellular ROS. Mechanistically, we define a signaling axis linking PIM1 to Drp1 and mitochondrial fission in lung cancer. PIM inhibition significantly increased the protein levels and mitochondrial localization of Drp1, causing marked fragmentation of mitochondria. An inverse correlation between PIM1 and Drp1 was confirmed in NSCLC patient samples. Inhibition of PIM sensitized NSCLC to chemotherapy and produced a synergistic anti-tumor response in vitro and in vivo. Immunohistochemistry and transmission electron microscopy verified that PIM inhibitors promote mitochondrial fission and apoptosis in vivo. These data improve our knowledge about how PIM1 regulates mitochondria and provide justification for combining PIM inhibition with chemotherapy in NSCLC.

cancer biology↗