Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches
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.
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.Attached Files
Published - e2025167118.full.pdf
Supplemental Material - pnas.2025167118.sapp.pdf
Supplemental Material - pnas.2025167118.sd01.xlsx
Files
Additional details
- PMCID
- PMC8106303
- Eprint ID
- 108861
- Resolver ID
- CaltechAUTHORS:20210429-075617746
- 1709-17844
- Instituto Serrapilheira
- R21OD028874
- NIH
- IOS-1645199
- NSF
- Created
-
2021-04-29Created from EPrint's datestamp field
- Updated
-
2023-07-18Created from EPrint's last_modified field