PMID- 22222209
OWN - NLM
STAT- MEDLINE
DCOM- 20120320
LR  - 20211021
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 424
IP  - 1
DP  - 2012 Mar 1
TI  - Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine 
      reproductive and respiratory syndrome virus GP4 glycoprotein and its 
      co-localization with CD163 in lipid rafts.
PG  - 18-32
LID - 10.1016/j.virol.2011.12.009 [doi]
AB  - The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 
      (GP4) resembles a typical type I membrane protein in its structure but lacks a 
      hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored 
      membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known 
      glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs 
      were made to substitute the GPI-anchor domain of DAF with the putative 
      lipid-anchor domain of GP4, and their membrane association and lipase cleavage 
      were determined in cells. The DAF-GP4 fusion protein was transported to the 
      plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C 
      (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. 
      Mutational studies for residues adjacent to the GPI modification site and 
      characterization of respective mutant viruses generated from infectious cDNA 
      clones show that the ability of GP4 for membrane association corresponded to 
      virus viability and growth characteristics. The residues T158 (omega-2, where omega is 
      the GPI moiety at E160), P159 (omega-1), and M162 (omega+2) of GP4 were determined to be 
      important for virus replication, with M162 being of particular importance for 
      virus infectivity. The complete removal of the peptide-anchor domain in GP4 
      resulted in a complete loss of virus infectivity. The depletion of cholesterol 
      from the plasma membrane of cells reduced the virus production, suggesting a role 
      of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with 
      CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as 
      a cellular receptor for PRRSV and GP4 has been shown to interact with this 
      receptor, our data implicates an important role of lipid rafts during entry of 
      the virus.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Du, Yijun
AU  - Du Y
AD  - Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, 
      IL 61802, USA.
FAU - Pattnaik, Asit K
AU  - Pattnaik AK
FAU - Song, Cheng
AU  - Song C
FAU - Yoo, Dongwan
AU  - Yoo D
FAU - Li, Gang
AU  - Li G
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120104
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD163 antigen)
RN  - 0 (CD55 Antigens)
RN  - 0 (Glycosylphosphatidylinositols)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Virus)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, CD/genetics/*metabolism
MH  - Antigens, Differentiation, Myelomonocytic/genetics/*metabolism
MH  - CD55 Antigens/genetics/metabolism
MH  - Cell Line
MH  - Glycosylphosphatidylinositols/*metabolism
MH  - Humans
MH  - Membrane Microdomains/*metabolism/virology
MH  - Molecular Sequence Data
MH  - Porcine Reproductive and Respiratory Syndrome/genetics/*metabolism/virology
MH  - Porcine respiratory and reproductive syndrome virus/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Receptors, Virus/genetics/metabolism
MH  - Sequence Alignment
MH  - Swine
MH  - Viral Envelope Proteins/chemistry/genetics/*metabolism
PMC - PMC7111931
EDAT- 2012/01/10 06:00
MHDA- 2012/03/21 06:00
PMCR- 2012/01/04
CRDT- 2012/01/07 06:00
PHST- 2011/09/21 00:00 [received]
PHST- 2011/10/22 00:00 [revised]
PHST- 2011/12/11 00:00 [accepted]
PHST- 2012/01/07 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/03/21 06:00 [medline]
PHST- 2012/01/04 00:00 [pmc-release]
AID - S0042-6822(11)00569-1 [pii]
AID - 10.1016/j.virol.2011.12.009 [doi]
PST - ppublish
SO  - Virology. 2012 Mar 1;424(1):18-32. doi: 10.1016/j.virol.2011.12.009. Epub 2012 
      Jan 4.