Hepatitis C virus (HCV)-induced immunoglobulin hypermutation reduces the affinity and neutralizing activities of antibodies against HCV envelope protein.

Journal of Virology
Keigo MachidaMichael M C Lai

Abstract

Hepatitis C virus (HCV) often causes persistent infection despite the presence of neutralizing antibodies against the virus in the sera of hepatitis C patients. HCV infects both hepatocytes and B cells through the binding of its envelope glycoprotein E2 to CD81, the putative viral receptor. Previously, we have shown that E2-CD81 interaction induces hypermutation of heavy-chain immunoglobulin (V(H)) in B cells. We hypothesize that if HCV infects antibody-producing B cells, the resultant hypermutation of V(H) may lower the affinity and specificity of the HCV-specific antibodies, enabling HCV to escape from immune surveillance. To test this hypothesis, we infected human hybridoma clones producing either neutralizing or non-neutralizing anti-E2 or anti-E1 antibodies with a lymphotropic HCV (SB strain). All of the hybridoma clones, except for a neutralizing antibody-producing hybridoma, could be infected with HCV and support virus replication for at least 8 weeks after infection. The V(H) sequences in the infected hybridomas had a significantly higher mutation frequency than those in the uninfected hybridomas, with mutations concentrating in complementarity-determining region 3. These mutations lowered the antibody affinity against ...Continue Reading

References

Jul 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·J D FingerothD T Fearon
Jan 1, 1995·Annual Review of Immunology·D T Fearon, R H Carter
Dec 1, 1996·Digestive Diseases and Sciences·S J Hadziyannis
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·M YanagiJ Bukh
Oct 6, 1997·Annals of Internal Medicine·E ZuckermanT L Fong
Oct 30, 1998·Science·P PileriS Abrignani
Feb 27, 1999·Current Opinion in Immunology·G Kelsoe
Apr 25, 2000·Journal of Virology·R PetraccaG Grandi
Aug 29, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T F BaumertT J Liang
Dec 22, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K M ChangF V Chisari
Jul 21, 2001·Molecular Cell·V N IvanovZ Ronai
Aug 2, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M LechmannT J Liang
Nov 21, 2001·The Journal of Experimental Medicine·R ThimmeF V Chisari
Jan 10, 2002·The Journal of Experimental Medicine·Stefania CrottaNicholas M Valiante
Jul 12, 2002·The New England Journal of Medicine·Olivier HermineXavier Troussard
Aug 3, 2002·Leukemia & Lymphoma·Daniela GasparottoMauro Boiocchi
Aug 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alberto Martin, Matthew D Scharff
Nov 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Robert ThimmeFrancis V Chisari
Dec 25, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ming QiaoT Jake Liang
Mar 18, 2003·The American Journal of the Medical Sciences·Marlyn J Mayo
Mar 21, 2003·European Journal of Immunology·Elisabetta SoldainiSergio Abrignani
Aug 15, 2003·Leukemia & Lymphoma·Wen-Kai Weng, Shoshana Levy
Sep 13, 2003·Journal of Virology·Laurence CocquerelShoshana Levy
Nov 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Birke BartoschRobert H Purcell
Nov 25, 2003·The New England Journal of Medicine·Alexandra M LevineMichael M C Lai
Feb 6, 2004·Nature Immunology·Stefano CasolaKlaus Rajewsky
Mar 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Keigo MachidaMichael M C Lai
Sep 16, 2004·European Journal of Immunology·Francesca MasciopintoSergio Abrignani
Oct 28, 2004·Gastroenterology·T Jake Liang, Theo Heller

❮ Previous
Next ❯

Citations

Aug 18, 2010·Viral Immunology·Erika A EksiogluChen Liu
Jul 16, 2011·Hepatitis Research and Treatment·Yasuteru KondoTooru Shimosegawa
Apr 21, 2012·International Journal of Microbiology·Yasuteru KondoTooru Shimosegawa
Jan 8, 2013·BMC Medicine·Michela FlegoStefano Vella
Jun 5, 2010·PLoS Pathogens·Jean-Pierre VartanianSimon Wain-Hobson
Nov 10, 2009·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Noha HassunaLynda J Partridge
Dec 4, 2012·Viruses·Samira Fafi-KremerThomas F Baumert
Dec 7, 2013·World Journal of Gastroenterology : WJG·Yasuteru Kondo, Tooru Shimosegawa
Apr 8, 2014·World Journal of Gastroenterology : WJG·Nora A FierroArturo Panduro
May 28, 2014·The Journal of Experimental Medicine·Katharina NothelferArmelle Phalipon
Nov 16, 2011·ISRN Hematology·Kyoko Tsukiyama-KoharaMichinori Kohara
Jul 17, 2009·Kidney International·Edgar D Charles, Lynn B Dustin
Oct 29, 2010·Journal of Medical Virology·Yuu ShimozumaMichio Imawari
Apr 5, 2013·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yasuteru KondoTooru Shimosegawa
Nov 4, 2011·The Journal of General Virology·Victoria C EdwardsJonathan K Ball
Mar 4, 2014·Antiviral Research·Jonathan K BallJane A McKeating
Feb 11, 2015·Nature Reviews. Microbiology·Katharina NothelferArmelle Phalipon
Dec 15, 2015·PloS One·Arturo Ramon Vargas CorreaLuciana Barros de Arruda
Dec 19, 2017·Nature Reviews. Immunology·Mirela Kuka, Matteo Iannacone
Dec 5, 2014·World Journal of Gastroenterology : WJG·Tawfik KhouryMeir Mizrahi
Apr 29, 2020·Cold Spring Harbor Perspectives in Medicine·Mansun Law

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Engineering

Antibody engineering technologies are constantly advancing to improve the clinical effectiveness of monoclonal and bispecific antibodies. Discover the latest research on Antibody Engineering here.