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Publication : Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice.

First Author  Schwarz MM Year  2023
Journal  Sci Adv Volume  9
Issue  28 Pages  eadh2264
PubMed ID  37450601 Mgi Jnum  J:338364
Mgi Id  MGI:7510683 Doi  10.1126/sciadv.adh2264
Citation  Schwarz MM, et al. (2023) Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice. Sci Adv 9(28):eadh2264
abstractText  Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice.
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