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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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2021-05, Vol.118 (18), p.1-3 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | 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. |
| 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. |
| doi_str_mv | 10.1073/pnas.2025167118 |
| format | Article |
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F. ; Lovell, Peter V. ; Friedrich, Samantha R. ; Olson, Christopher R. ; Miles, Joshua ; Mueller, Paul A. ; Tavori, Hagai ; Fazio, Sergio ; Lois, Carlos ; Mello, Claudio V.</creator><creatorcontrib>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.</creatorcontrib><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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2025167118</identifier><identifier>PMID: 33903244</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biological Sciences ; Biological Transport - genetics ; BRIEF REPORTS ; Cellular structure ; Cholesterol ; Cholesterol - genetics ; Cholesterol - metabolism ; Density ; Divergence ; Domains ; Finches - blood ; Finches - genetics ; Gene Expression Regulation - genetics ; Genetics ; Glycoproteins ; High density lipoprotein ; Humans ; Infectivity ; Ligands ; Lipids ; Lipids - blood ; Lipoproteins ; Low density lipoprotein receptors ; Membrane Glycoproteins - genetics ; Receptor density ; Receptors ; Receptors, LDL - blood ; Receptors, LDL - genetics ; Songbirds ; Stomatitis ; Structure-function relationships ; Vertebrates ; Viral Envelope Proteins - genetics ; Viruses</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-05, Vol.118 (18), p.1-3</ispartof><rights>Copyright © 2021 the Author(s). 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F.</au><au>Lovell, Peter V.</au><au>Friedrich, Samantha R.</au><au>Olson, Christopher R.</au><au>Miles, Joshua</au><au>Mueller, Paul A.</au><au>Tavori, Hagai</au><au>Fazio, Sergio</au><au>Lois, Carlos</au><au>Mello, Claudio V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2021-05-04</date><risdate>2021</risdate><volume>118</volume><issue>18</issue><spage>1</spage><epage>3</epage><pages>1-3</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><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). 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| subjects | Animals Biological Sciences Biological Transport - genetics BRIEF REPORTS Cellular structure Cholesterol Cholesterol - genetics Cholesterol - metabolism Density Divergence Domains Finches - blood Finches - genetics Gene Expression Regulation - genetics Genetics Glycoproteins High density lipoprotein Humans Infectivity Ligands Lipids Lipids - blood Lipoproteins Low density lipoprotein receptors Membrane Glycoproteins - genetics Receptor density Receptors Receptors, LDL - blood Receptors, LDL - genetics Songbirds Stomatitis Structure-function relationships Vertebrates Viral Envelope Proteins - genetics Viruses |
| title | Divergent low-density lipoprotein receptor (LDLR) linked to low VSV G-dependent viral infectivity and unique serum lipid profile in zebra finches |
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