Ghent University Academic Bibliography

Advanced

A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo

Philip Meuleman UGent, Maria Teresa Catanese, Lieven Verhoye UGent, Isabelle Desombere UGent, Aliasghar Farhoudi Moghadam UGent, Christopher T Jones, Timothy Sheahan, Katarzyna Grzyb, Riccardo Cortese and Charles M Rice, et al. (2012) HEPATOLOGY. 55(2). p.364-372
abstract
Endstage liver disease caused by chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the Western world. However, immediate reinfection of the grafted donor liver by circulating virus is inevitable and liver disease progresses much faster than the original disease. Standard antiviral therapy is not well tolerated and usually ineffective in liver transplant patients, whereas anti-HCV immunotherapy is hampered by the extreme genetic diversity of the virus and its ability to spread by way of cell-cell contacts. We generated a human monoclonal antibody against scavenger receptor class B type I (SR-BI), monoclonal antibody (mAb)16-71, which can efficiently prevent infection of Huh-7.5 hepatoma cells and primary hepatocytes by cell-culture-derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated that mAb16-71 interferes with direct cell-to-cell transmission of HCV. Finally we evaluated the in vivo efficacy of mAb16-71 in human liver urokinase-type plasminogen activator, severe combined immune deficiency (uPA-SCID) mice (chimeric mice). A 2-week anti-SR-BI therapy that was initiated 1 day before viral inoculation completely protected all chimeric mice from infection with serum-derived HCV of different genotypes. Moreover, a 9-day postexposure therapy that was initiated 3 days after viral inoculation (when viremia was already observed in the animals) suppressed the rapid viral spread observed in untreated control animals. After cessation of anti-SR-BI-specific antibody therapy, a rise of the viral load was observed. Conclusion: Using in vitro cell culture and human liver-chimeric mouse models, we show that a human mAb targeting the HCV coreceptor SR-BI completely prevents infection and intrahepatic spread of multiple HCV genotypes. This strategy may be an efficacious way to prevent infection of allografts following liver transplantation in chronic HCV patients, and may even hold promise for the prevention of virus rebound during or following antiviral therapy.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GENOTYPE 1 INFECTION, UPA-SCID MOUSE, TO-CELL TRANSMISSION, HEPATOMA-CELLS, CD81, CULTURE, ENTRY, ANTIVIRAL THERAPY, LIVER-TRANSPLANTATION, NEUTRALIZING ANTIBODIES
journal title
HEPATOLOGY
Hepatology
volume
55
issue
2
pages
364 - 372
Web of Science type
Article
Web of Science id
000299632900005
JCR category
GASTROENTEROLOGY & HEPATOLOGY
JCR impact factor
12.003 (2012)
JCR rank
2/73 (2012)
JCR quartile
1 (2012)
ISSN
0270-9139
DOI
10.1002/hep.24692
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2066059
handle
http://hdl.handle.net/1854/LU-2066059
date created
2012-03-14 14:14:44
date last changed
2012-04-10 08:46:00
@article{2066059,
  abstract     = {Endstage liver disease caused by chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the Western world. However, immediate reinfection of the grafted donor liver by circulating virus is inevitable and liver disease progresses much faster than the original disease. Standard antiviral therapy is not well tolerated and usually ineffective in liver transplant patients, whereas anti-HCV immunotherapy is hampered by the extreme genetic diversity of the virus and its ability to spread by way of cell-cell contacts. We generated a human monoclonal antibody against scavenger receptor class B type I (SR-BI), monoclonal antibody (mAb)16-71, which can efficiently prevent infection of Huh-7.5 hepatoma cells and primary hepatocytes by cell-culture-derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated that mAb16-71 interferes with direct cell-to-cell transmission of HCV. Finally we evaluated the in vivo efficacy of mAb16-71 in human liver urokinase-type plasminogen activator, severe combined immune deficiency (uPA-SCID) mice (chimeric mice). A 2-week anti-SR-BI therapy that was initiated 1 day before viral inoculation completely protected all chimeric mice from infection with serum-derived HCV of different genotypes. Moreover, a 9-day postexposure therapy that was initiated 3 days after viral inoculation (when viremia was already observed in the animals) suppressed the rapid viral spread observed in untreated control animals. After cessation of anti-SR-BI-specific antibody therapy, a rise of the viral load was observed. Conclusion: Using in vitro cell culture and human liver-chimeric mouse models, we show that a human mAb targeting the HCV coreceptor SR-BI completely prevents infection and intrahepatic spread of multiple HCV genotypes. This strategy may be an efficacious way to prevent infection of allografts following liver transplantation in chronic HCV patients, and may even hold promise for the prevention of virus rebound during or following antiviral therapy.},
  author       = {Meuleman, Philip and Catanese, Maria Teresa and Verhoye, Lieven and Desombere, Isabelle and Farhoudi Moghadam, Aliasghar and Jones, Christopher T and Sheahan, Timothy and Grzyb, Katarzyna and Cortese, Riccardo and Rice, Charles M and Leroux-Roels, Geert and Nicosia, Alfredo},
  issn         = {0270-9139},
  journal      = {HEPATOLOGY},
  keyword      = {GENOTYPE 1 INFECTION,UPA-SCID MOUSE,TO-CELL TRANSMISSION,HEPATOMA-CELLS,CD81,CULTURE,ENTRY,ANTIVIRAL THERAPY,LIVER-TRANSPLANTATION,NEUTRALIZING ANTIBODIES},
  language     = {eng},
  number       = {2},
  pages        = {364--372},
  title        = {A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo},
  url          = {http://dx.doi.org/10.1002/hep.24692},
  volume       = {55},
  year         = {2012},
}

Chicago
Meuleman, Philip, Maria Teresa Catanese, Lieven Verhoye, Isabelle Desombere, Aliasghar Farhoudi Moghadam, Christopher T Jones, Timothy Sheahan, et al. 2012. “A Human Monoclonal Antibody Targeting Scavenger Receptor Class B Type I Precludes Hepatitis C Virus Infection and Viral Spread in Vitro and in Vivo.” Hepatology 55 (2): 364–372.
APA
Meuleman, P., Catanese, M. T., Verhoye, L., Desombere, I., Farhoudi Moghadam, A., Jones, C. T., Sheahan, T., et al. (2012). A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo. HEPATOLOGY, 55(2), 364–372.
Vancouver
1.
Meuleman P, Catanese MT, Verhoye L, Desombere I, Farhoudi Moghadam A, Jones CT, et al. A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo. HEPATOLOGY. 2012;55(2):364–72.
MLA
Meuleman, Philip, Maria Teresa Catanese, Lieven Verhoye, et al. “A Human Monoclonal Antibody Targeting Scavenger Receptor Class B Type I Precludes Hepatitis C Virus Infection and Viral Spread in Vitro and in Vivo.” HEPATOLOGY 55.2 (2012): 364–372. Print.