Antibody-Dependent Enhancement of Ebola Virus Infection

ABSTRACT Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the Zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and by complement component C1q. Our results suggest a novel mechanism of antibody-dependent enhancement of Ebola virus infection, one that would account for the dire outcome of Ebola outbreaks in human populations.

[1]  Shinji Watanabe,et al.  Identification of Protective Epitopes on Ebola Virus Glycoprotein at the Single Amino Acid Level by Using Recombinant Vesicular Stomatitis Viruses , 2003, Journal of Virology.

[2]  P. Jahrling,et al.  Evidence against an important role for infectivity-enhancing antibodies in Ebola virus infections. , 2002, Virology.

[3]  Y. Kawaoka,et al.  The pathogenesis of Ebola hemorrhagic fever. , 2001, Trends in microbiology.

[4]  G. Neumann,et al.  Ebola Virus VP40-Induced Particle Formation and Association with the Lipid Bilayer , 2001, Journal of Virology.

[5]  Shinji Watanabe,et al.  Infectivity-Enhancing Antibodies to Ebola Virus Glycoprotein , 2001, Journal of Virology.

[6]  C. Issel,et al.  In vitro antibody-dependent enhancement assays are insensitive indicators of in vivo vaccine enhancement of equine infectious anemia virus. , 1999, Virology.

[7]  D. Haburchak,et al.  Topley and Wilson's Microbiology and Microbial Infections , 1999 .

[8]  P. Debré,et al.  Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients , 1999, Nature Medicine.

[9]  L. Klickstein,et al.  C1q-binding proteins and C1q receptors. , 1999, Current opinion in immunology.

[10]  A. Rowe,et al.  Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. , 1999, The Journal of infectious diseases.

[11]  Ignatyev Gm.  Immune response to filovirus infections. , 1999 .

[12]  J. McCormick,et al.  Experimental filovirus infections. , 1999, Current topics in microbiology and immunology.

[13]  G. Ignatyev,et al.  Immune response to filovirus infections. , 1999, Current topics in microbiology and immunology.

[14]  H. Feldmann,et al.  Classification, structure, and replication of filoviruses. , 1999, Current topics in microbiology and immunology.

[15]  H. Feldmann,et al.  Molecular pathogenesis of filovirus infections: role of macrophages and endothelial cells. , 1999, Current topics in microbiology and immunology.

[16]  P. Eggleton,et al.  C1q--how many functions? How many receptors? , 1998, Trends in cell biology.

[17]  P. Bates,et al.  Characterization of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of Receptor-Deficient Cell Lines , 1998, Journal of Virology.

[18]  S. Meri.  Complement Fixation Test , 1998 .

[19]  Max Sussman,et al.  Topley and Wilson's Microbiology and Microbial infections , 1998 .

[20]  I. Roitt,et al.  Encyclopedia of immunology , 1998 .

[21]  A. Sanchez,et al.  A system for functional analysis of Ebola virus glycoprotein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Füst.  Enhancing antibodies in HIV infection , 1997, Parasitology.

[23]  N. Thielens,et al.  Two parallel routes of the complement‐mediated antibody‐dependent enhancement of HIV‐1 infection , 1997, AIDS.

[24]  U. Krüger,et al.  Complement activation by HIV-1-infected cells: the role of transmembrane glycoprotein gp41. , 1997, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[25]  J. Ravetch.  Fc receptors. , 1997, Current opinion in immunology.

[26]  A. Sanchez,et al.  The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  V. Volchkov,et al.  GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. , 1995, Virology.

[28]  M. Bloom,et al.  Aleutian mink disease parvovirus infection of mink macrophages and human macrophage cell line U937: demonstration of antibody-dependent enhancement of infection , 1993, Journal of virology.

[29]  H. Ochiai,et al.  Infection enhancement of influenza A NWS virus in primary murine macrophages by anti‐hemagglutinin monoclonal antibody , 1992, Journal of medical virology.

[30]  K.,et al.  Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages , 1992, Journal of virology.

[31]  D. Montefiori,et al.  ANTIBODY-DEPENDENT ENHANCEMENT OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION , 1988, The Lancet.

[32]  J. S. Porterfield.  Antibody-dependent enhancement of viral infectivity. , 1986, Advances in virus research.

[33]  S. Lylecummins.  [Complement fixation test]. , 1982, Zentralblatt fur Bakteriologie, Mikrobiologie und Hygiene. 1. Abt. Originale A, Medizinische Mikrobiologie, Infektionskrankheiten und Parasitologie = International journal of microbiology and hygiene. A, Medical microbiology, infectious....

[34]  M. Frank,et al.  Complement receptors. , 1981, Clinical immunology reviews.

[35]  SB Halstead,et al.  Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody , 1977, The Journal of experimental medicine.