The association of hepatitis C virus glycoproteins with apolipoproteins E and B early in assembly is conserved in lipoviral particles.
In patients chronically infected with hepatitis C virus and in the HCV cell culture system (HCVcc), it is known that highly infectious virus particles have low to very low buoyant densities. These low densities have been attributed to the association of HCV with lipoprotein components, which occur during the viral morphogenesis. The resulting hybrid particles are known as lipoviral particles (LVP); however, very little is known about how these particles are created. In our study, we used Huh7.5 cells to investigate the intracellular association between envelope proteins and apolipoproteins B and E (ApoB and ApoE, respectively). In particular, we were interested in the role of this association in initiating LVP morphogenesis. Co-immunoprecipitation assays revealed that ApoB, ApoE, and HCV glycoproteins formed a protein complex early in the HCV lifecycle. Confocal analyses of naïve, E1E2-transduced and HCVcc-infected cells showed that HCV glycoproteins, ApoB and ApoE were found strongly colocalized only in the endoplasmic reticulum. We also found that HCV glycoproteins, ApoB and ApoE were already associated with intracellular infectious viral particles and, furthermore, that the protein complex was conserved in the infectious viral particles present in the supernatant of infected Huh7.5 cells. The association of HCV glycoproteins with ApoE was also evidenced in the HCVpp system, using the non-hepatic HEK293T cell line. We suggest that the complex formed by HCV E1E2, ApoB, and ApoE may initiate lipoviral particle morphogenesis.
From the INSERM U966, Université François Rabelais and CHRU de Tours, 37032 Tours, France.
Audrey
A
Boyer
From the INSERM U966, Université François Rabelais and CHRU de Tours, 37032 Tours, France.
Amélie
A
Dumans
From the INSERM U966, Université François Rabelais and CHRU de Tours, 37032 Tours, France.
Elodie
E
Beaumont
From the INSERM U966, Université François Rabelais and CHRU de Tours, 37032 Tours, France.
Loïc
L
Etienne
From the INSERM U966, Université François Rabelais and CHRU de Tours, 37032 Tours, France.
Philippe
P
Roingeard
From the INSERM U966, Université François Rabelais and CHRU de Tours, 37032 Tours, France Jean.meunier@univ-tours.fr.
Jean-Christophe
JC
Meunier
D001055:Apolipoproteins B / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000378:metabolism*; D019065:Virus Assembly
D001055:Apolipoproteins B; D001057:Apolipoproteins E; C087035:E1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus
Apolipoprotein; Glycoprotein; Hepatitis C Virus (HCV); Lipoprotein; Morphogenesis