Year: 2023
Type: article
Abstract: 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.
Source: Science Advances
Institutions: University of Pittsburgh, Washington University in St. Louis
Language: English
Topic: Viral Infections and Vectors
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G196865702, G2828277731, Comparative Analysis of Bunyavirus Neuropathogenesis, Identification and Characterization of Entry Factors Critical for Rift Valley Fever Virus Infection and Pathogenesis, Characterizing the role of LDL related receptor 1 (Lrp1) as host entry factor for multiple bunyaviruses, Live-attenuated Rift Valley fever vaccines: comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses
OpenAlex ID: W4384296889