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Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches

The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks domains critical for ligand binding and cellular trafficking, inc...

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Autores principales: Velho, Tarciso A. F., Lovell, Peter V., Friedrich, Samantha R., Olson, Christopher R., Miles, Joshua, Mueller, Paul A., Tavori, Hagai, Fazio, Sergio, Lois, Carlos, Mello, Claudio V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106303/
https://www.ncbi.nlm.nih.gov/pubmed/33903244
http://dx.doi.org/10.1073/pnas.2025167118
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author Velho, Tarciso A. F.
Lovell, Peter V.
Friedrich, Samantha R.
Olson, Christopher R.
Miles, Joshua
Mueller, Paul A.
Tavori, Hagai
Fazio, Sergio
Lois, Carlos
Mello, Claudio V.
author_facet Velho, Tarciso A. F.
Lovell, Peter V.
Friedrich, Samantha R.
Olson, Christopher R.
Miles, Joshua
Mueller, Paul A.
Tavori, Hagai
Fazio, Sergio
Lois, Carlos
Mello, Claudio V.
author_sort Velho, Tarciso A. F.
collection PubMed
description The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks domains critical for ligand binding and cellular trafficking, inconsistent with universal structure conservation and function across vertebrates. Linked to the LDLR functional domain loss, zebra finches show inefficient infectivity by lentiviruses (LVs) pseudotyped with VSV G, which can be rescued by the expression of human LDLR. Finches also show an atypical plasma lipid distribution that relies largely on high-density lipoprotein (HDL). These findings provide insights into the genetics and evolution of viral infectivity and cholesterol transport mechanisms in vertebrates.
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spelling pubmed-81063032021-05-12 Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches Velho, Tarciso A. F. Lovell, Peter V. Friedrich, Samantha R. Olson, Christopher R. Miles, Joshua Mueller, Paul A. Tavori, Hagai Fazio, Sergio Lois, Carlos Mello, Claudio V. Proc Natl Acad Sci U S A Biological Sciences The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks domains critical for ligand binding and cellular trafficking, inconsistent with universal structure conservation and function across vertebrates. Linked to the LDLR functional domain loss, zebra finches show inefficient infectivity by lentiviruses (LVs) pseudotyped with VSV G, which can be rescued by the expression of human LDLR. Finches also show an atypical plasma lipid distribution that relies largely on high-density lipoprotein (HDL). These findings provide insights into the genetics and evolution of viral infectivity and cholesterol transport mechanisms in vertebrates. National Academy of Sciences 2021-05-04 2021-04-26 /pmc/articles/PMC8106303/ /pubmed/33903244 http://dx.doi.org/10.1073/pnas.2025167118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Velho, Tarciso A. F.
Lovell, Peter V.
Friedrich, Samantha R.
Olson, Christopher R.
Miles, Joshua
Mueller, Paul A.
Tavori, Hagai
Fazio, Sergio
Lois, Carlos
Mello, Claudio V.
Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
title Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
title_full Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
title_fullStr Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
title_full_unstemmed Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
title_short Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
title_sort divergent low-density lipoprotein receptor (ldlr) linked to low vsv g-dependent viral infectivity and unique serum lipid profile in zebra finches
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106303/
https://www.ncbi.nlm.nih.gov/pubmed/33903244
http://dx.doi.org/10.1073/pnas.2025167118
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