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Open Access Research article

Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines

Satoshi Taniguchi12, Yusuke Sayama13, Noriyo Nagata4, Tetsuro Ikegami5, Mary E Miranda6, Shumpei Watanabe1, Itoe Iizuka17, Shuetsu Fukushi1, Tetsuya Mizutani1, Yoshiyuki Ishii2, Masayuki Saijo1, Hiroomi Akashi8, Yasuhiro Yoshikawa2, Shigeru Kyuwa2 and Shigeru Morikawa1*

Author Affiliations

1 Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan

2 Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

3 Department of Virology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan

4 Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan

5 Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Mary Moody Northen Pavilion 3.206D, 301 University Boulevard Galveston, Texas, TX, 77555-0436, USA

6 Veterinary Public Health Specialist, Aralia St., Ayala Westgrove Heights, Silang, Cavite, 4118, Philippines

7 Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

8 Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

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BMC Veterinary Research 2012, 8:189  doi:10.1186/1746-6148-8-189

Published: 11 October 2012

Abstract

Background

Ebolaviruses induce lethal viral hemorrhagic fevers (VHFs) in humans and non-human primates, with the exceptions of Reston virus (RESTV), which is not pathogenic for humans. In human VHF cases, extensive analyses of the humoral immune responses in survivors and non-survivors have shown that the IgG responses to nucleoprotein (NP) and other viral proteins are associated with asymptomatic and survival outcomes, and that the neutralizing antibody responses targeting ebolaviruses glycoprotein (GP1,2) are the major indicator of protective immunity. On the other hand, the immune responses in non-human primates, especially naturally infected ones, have not yet been elucidated in detail, and the significance of the antibody responses against NP and GP1,2 in RESTV-infected cynomolgus macaques is still unclear. In this study, we analyzed the humoral immune responses of cynomolgus macaque by using serum specimens obtained from the RESTV epizootic in 1996 in the Philippines to expand our knowledge on the immune responses in naturally RESTV-infected non-human primates.

Results

The antibody responses were analyzed using IgG-ELISA, an indirect immunofluorescent antibody assay (IFA), and a pseudotyped VSV-based neutralizing (NT) assay. Antigen-capture (Ag)-ELISA was also performed to detect viral antigens in the serum specimens. We found that the anti-GP1,2 responses, but not the anti-NP responses, closely were correlated with the neutralization responses, as well as the clearance of viremia in the sera of the RESTV-infected cynomolgus macaques. Additionally, by analyzing the cytokine/chemokine concentrations of these serum specimens, we found high concentrations of proinflammatory cytokines/chemokines, such as IFNγ, IL8, IL-12, and MIP1α, in the convalescent phase sera.

Conclusions

These results imply that both the antibody response to GP1,2 and the proinflammatory innate responses play significant roles in the recovery from RESTV infection in cynomolgus macaques.

Keywords:
Ebola; Ebolavirus; Reston virus; Reston ebolavirus; Filovirus; Zoonosis; Humoral immune response; Cynomolgus macaque; Cytokine; Antibody