Specific acquisition of functional CD59 but not CD46 or CD55 by hepatitis C virus.
Viruses of different families encode for regulators of the complement system (RCAs) or acquire such RCAs from the host to get protection against complement-mediated lysis (CML). As hepatitis C virus (HCV) shares no genetic similarity to any known RCA and is detectable at high titers in sera of infected individuals, we investigated whether HCV has adapted host-derived RCAs to resist CML. Here we report that HCV selectively incorporates CD59 while neither CD55, nor CD46 are associated with the virus. The presence of CD59 was shown by capture assays using patient- and cell culture-derived HCV isolates. Association of CD59 with HCV was further confirmed by Western blot analysis using purified viral supernatants from infected Huh 7.5 cells. HCV captured by antibodies specific for CD59 remained infectious for Huh 7.5 cells. In addition, blocking of CD59 in the presence of active complement reduced the titer of HCV most likely due to CML. HCV produced in CD59 knock-down cells were more significantly susceptible to CML compared to wild type virus, but neither replication, assembly nor infectivity of the virus seemed to be impaired in the absence of CD59. In summary our data indicate that HCV incorporates selectively CD59 in its envelope to gain resistance to CML in serum of infected individuals.
Institute of Virology, Innsbruck Medical University, Innsbruck, Austria.
Asim
A
Ejaz
Eike
E
Steinmann
Zoltán
Z
Bánki
Anggakusuma
Sana
S
Khalid
Susanne
S
Lengauer
Corinne
C
Wilhelm
Heinz
H
Zoller
Anna
A
Schloegl
Joerg
J
Steinmann
Elena
E
Grabski
Michael
M
Kleines
Thomas
T
Pietschmann
Heribert
H
Stoiber
D000328:Adult; D000368:Aged; D018958:CD55 Antigens / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000276:immunology; D003165:Complement System Proteins; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005838:Genotype; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008297:Male; D051916:Membrane Cofactor Protein / Q000378:metabolism*; D008875:Middle Aged
D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; D051916:Membrane Cofactor Protein; D003165:Complement System Proteins