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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number2025167118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number18
DOIs
StatePublished - May 4 2021

Keywords

  • Cholesterol
  • LDLR
  • Lentivirus
  • VSG G
  • Viral transduction

ASJC Scopus subject areas

  • General

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