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Increased expression of LDL receptor-related protein 1 during human cytomegalovirus infection reduces virion cholesterol and infectivity.

Abstract：

:In response to virus infection, cells can alter protein expression to modify cellular functions and limit viral replication. To examine host protein expression during infection with human cytomegalovirus (HCMV), an enveloped DNA virus, we performed a semiquantitative, temporal analysis of the cell surface proteome in infected fibroblasts. We determined that resident low density lipoprotein related receptor 1 (LRP1), a plasma membrane receptor that regulates lipid metabolism, is elevated early after HCMV infection, resulting in decreased intracellular cholesterol. siRNA knockdown or antibody-mediated inhibition of LRP1 increased intracellular cholesterol and concomitantly increased the infectious virus yield. Virions produced under these conditions contained elevated cholesterol, resulting in increased infectivity. Depleting cholesterol from virions reduced their infectivity by blocking fusion of the virion envelope with the cell membrane. Thus, LRP1 restricts HCMV infectivity by controlling the availability of cholesterol for the virion envelope, and increased LRP1 expression is likely a defense response to infection.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Gudleski-O'Regan N,Greco TM,Cristea IM,Shenk T

doi

10.1016/j.chom.2012.05.012

subject

Has Abstract

pub_date

2012-07-19 00:00:00

pages

86-96

issue

1

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(12)00198-9

journal_volume

12

pub_type

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