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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

Velho, Tarciso A. F. and Lovell, Peter V. and Friedrich, Samantha R. and Olson, Christopher R. and Miles, Joshua and Mueller, Paul A. and Tavori, Hagai and Fazio, Sergio and Lois, Carlos and Mello, Claudio V. (2021) Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches. Proceedings of the National Academy of Sciences of the United States of America, 118 (18). Art. No. e2025167118. ISSN 0027-8424. PMCID PMC8106303. doi:10.1073/pnas.2025167118. https://resolver.caltech.edu/CaltechAUTHORS:20210429-075617746

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.2025167118DOIArticle
https://www.pnas.org/content/suppl/2021/04/25/2025167118.DCSupplementalPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8106303/PubMed CentralArticle
ORCID:
AuthorORCID
Velho, Tarciso A. F.0000-0001-6348-0011
Friedrich, Samantha R.0000-0003-0570-6080
Olson, Christopher R.0000-0002-8351-0633
Miles, Joshua0000-0003-0022-1965
Mueller, Paul A.0000-0001-9315-0152
Fazio, Sergio0000-0002-8145-8034
Lois, Carlos0000-0002-7305-2317
Mello, Claudio V.0000-0002-9826-8421
Additional Information:© 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). Edited by Scott V. Edwards, Harvard University, Cambridge, MA, and approved March 9, 2021 (received for review December 23, 2020). We thank Morgan Wirthlin for help with searches for an LDLR ortholog in early versions of the zebra finch genome assembly. This work was supported by funding from Instituto Serrapilheira (Grant 1709-17844 to T.A.F.V.), NIH/Office of Research Infrastructure Program (Grant R21OD028874 to C.V.M.) and NSF (Enabling Discovery Through Genomics Grant 1645199 to C.V.M., T.A.F.V., and C.L.). Data Availability: All study data are included in the article and/or supporting information. Author contributions: T.A.F.V., C.L., and C.V.M. designed research; T.A.F.V., P.V.L., S.R.F., C.R.O., J.M., P.A.M., H.T., and S.F. performed research; T.A.F.V., S.F., C.L., and C.V.M. contributed new reagents/analytic tools; T.A.F.V., P.V.L., P.A.M., H.T., and C.V.M. analyzed data; and T.A.F.V. and C.V.M. wrote the paper with input from all authors. The authors declare no competing interest. See online for related content such as Commentaries. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2025167118/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
Instituto Serrapilheira1709-17844
NIHR21OD028874
NSFIOS-1645199
Subject Keywords:cholesterol; LDLR; VSG G; lentivirus; viral transduction
Issue or Number:18
PubMed Central ID:PMC8106303
DOI:10.1073/pnas.2025167118
Record Number:CaltechAUTHORS:20210429-075617746
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210429-075617746
Official Citation:Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches. Tarciso A. F. Velho, Peter V. Lovell, Samantha R. Friedrich, Christopher R. Olson, Joshua Miles, Paul A. Mueller, Hagai Tavori, Sergio Fazio, Carlos Lois, Claudio V. Mello. Proceedings of the National Academy of Sciences May 2021, 118 (18) e2025167118; DOI: 10.1073/pnas.2025167118
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108861
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:29 Apr 2021 15:34
Last Modified:04 Aug 2021 23:45

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