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

Satoshi Taniguchi, Yusuke Sayama, Noriyo Nagata, Tetsuro Ikegami, Mary E. Miranda, Shumpei Watanabe, Itoe Iizuka, Shuetsu Fukushi, Tetsuya Mizutani, Yoshiyuki Ishii, Masayuki Saijo, Hiroomi Akashi, Yasuhiro Yoshikawa, Shigeru Kyuwa, Shigeru Morikawa

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number189
JournalBMC Veterinary Research
Volume8
DOIs
StatePublished - Oct 11 2012

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Philippines
Macaca fascicularis
Macaca
Humoral Immunity
humoral immunity
Disease Outbreaks
Viruses
viruses
nucleoproteins
Nucleoproteins
Antibody Formation
Viral Hemorrhagic Fevers
Ebolavirus
Primates
Serum
antibodies
chemokines
Chemokines
neutralization
fever

Keywords

  • Antibody
  • Cynomolgus macaque
  • Cytokine
  • Ebola
  • Ebolavirus
  • Filovirus
  • Humoral immune response
  • Reston ebolavirus
  • Reston virus
  • Zoonosis

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines. / Taniguchi, Satoshi; Sayama, Yusuke; Nagata, Noriyo; Ikegami, Tetsuro; Miranda, Mary E.; Watanabe, Shumpei; Iizuka, Itoe; Fukushi, Shuetsu; Mizutani, Tetsuya; Ishii, Yoshiyuki; Saijo, Masayuki; Akashi, Hiroomi; Yoshikawa, Yasuhiro; Kyuwa, Shigeru; Morikawa, Shigeru.

In: BMC Veterinary Research, Vol. 8, 189, 11.10.2012.

Research output: Contribution to journalArticle

Taniguchi, S, Sayama, Y, Nagata, N, Ikegami, T, Miranda, ME, Watanabe, S, Iizuka, I, Fukushi, S, Mizutani, T, Ishii, Y, Saijo, M, Akashi, H, Yoshikawa, Y, Kyuwa, S & Morikawa, S 2012, 'Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines', BMC Veterinary Research, vol. 8, 189. https://doi.org/10.1186/1746-6148-8-189
Taniguchi, Satoshi ; Sayama, Yusuke ; Nagata, Noriyo ; Ikegami, Tetsuro ; Miranda, Mary E. ; Watanabe, Shumpei ; Iizuka, Itoe ; Fukushi, Shuetsu ; Mizutani, Tetsuya ; Ishii, Yoshiyuki ; Saijo, Masayuki ; Akashi, Hiroomi ; Yoshikawa, Yasuhiro ; Kyuwa, Shigeru ; Morikawa, Shigeru. / Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines. In: BMC Veterinary Research. 2012 ; Vol. 8.
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AU - Ikegami, Tetsuro

AU - Miranda, Mary E.

AU - Watanabe, Shumpei

AU - Iizuka, Itoe

AU - Fukushi, Shuetsu

AU - Mizutani, Tetsuya

AU - Ishii, Yoshiyuki

AU - Saijo, Masayuki

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N2 - 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.

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KW - Zoonosis

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