TY - JOUR
T1 - Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
AU - Schwarz, Madeline M.
AU - Ganaie, Safder S.
AU - Feng, Annie
AU - Brown, Griffin
AU - Yangdon, Tenzin
AU - White, J. Michael
AU - Hoehl, Ryan M.
AU - McMillen, Cynthia M.
AU - Rush, Rachael E.
AU - Connors, Kaleigh A.
AU - Cui, Xiaoxia
AU - Leung, Daisy W.
AU - Egawa, Takeshi
AU - Amarasinghe, Gaya K.
AU - Hartman, Amy L.
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/7/12
Y1 - 2023/7/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85164759150&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adh2264
DO - 10.1126/sciadv.adh2264
M3 - Article
C2 - 37450601
AN - SCOPUS:85164759150
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 28
M1 - adh2264
ER -