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

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 re...

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Autores principales: Schwarz, Madeline M., Ganaie, Safder S., Feng, Annie, Brown, Griffin, Yangdon, Tenzin, White, J. Michael, Hoehl, Ryan M., McMillen, Cynthia M., Rush, Rachael E., Connors, Kaleigh A., Cui, Xiaoxia, Leung, Daisy W., Egawa, Takeshi, Amarasinghe, Gaya K., Hartman, Amy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348670/
https://www.ncbi.nlm.nih.gov/pubmed/37450601
http://dx.doi.org/10.1126/sciadv.adh2264
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author Schwarz, Madeline M.
Ganaie, Safder S.
Feng, Annie
Brown, Griffin
Yangdon, Tenzin
White, J. Michael
Hoehl, Ryan M.
McMillen, Cynthia M.
Rush, Rachael E.
Connors, Kaleigh A.
Cui, Xiaoxia
Leung, Daisy W.
Egawa, Takeshi
Amarasinghe, Gaya K.
Hartman, Amy L.
author_facet Schwarz, Madeline M.
Ganaie, Safder S.
Feng, Annie
Brown, Griffin
Yangdon, Tenzin
White, J. Michael
Hoehl, Ryan M.
McMillen, Cynthia M.
Rush, Rachael E.
Connors, Kaleigh A.
Cui, Xiaoxia
Leung, Daisy W.
Egawa, Takeshi
Amarasinghe, Gaya K.
Hartman, Amy L.
author_sort Schwarz, Madeline M.
collection PubMed
description 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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spelling pubmed-103486702023-07-15 Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice Schwarz, Madeline M. Ganaie, Safder S. Feng, Annie Brown, Griffin Yangdon, Tenzin White, J. Michael Hoehl, Ryan M. McMillen, Cynthia M. Rush, Rachael E. Connors, Kaleigh A. Cui, Xiaoxia Leung, Daisy W. Egawa, Takeshi Amarasinghe, Gaya K. Hartman, Amy L. Sci Adv Biomedicine and Life Sciences 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. American Association for the Advancement of Science 2023-07-14 /pmc/articles/PMC10348670/ /pubmed/37450601 http://dx.doi.org/10.1126/sciadv.adh2264 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Schwarz, Madeline M.
Ganaie, Safder S.
Feng, Annie
Brown, Griffin
Yangdon, Tenzin
White, J. Michael
Hoehl, Ryan M.
McMillen, Cynthia M.
Rush, Rachael E.
Connors, Kaleigh A.
Cui, Xiaoxia
Leung, Daisy W.
Egawa, Takeshi
Amarasinghe, Gaya K.
Hartman, Amy L.
Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
title Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
title_full Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
title_fullStr Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
title_full_unstemmed Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
title_short Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
title_sort lrp1 is essential for lethal rift valley fever hepatic disease in mice
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348670/
https://www.ncbi.nlm.nih.gov/pubmed/37450601
http://dx.doi.org/10.1126/sciadv.adh2264
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