Abstract
BackgroundEbolaviruses 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.ResultsThe 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.ConclusionsThese 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.
Highlights
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
We found that the antiGP1,2 responses, but not the anti-NP responses, were closely correlated with the neutralization antibody responses, as well as the clearance of viremia, in the sera of RESTV-infected cynomolgus macaques
RESTV NP-and GP1,2-specific antibodies, neutralizing antibody responses, and the viral antigens in the cynomolgus macaque sera from the 1996 RESTV epizootic Twenty-seven serum samples derived from cynomolgus macaques that were either found already dead or had been euthanized at the facility were available
Summary
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. 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. 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. Filoviruses induce lethal viral hemorrhagic fevers (VHFs) in both humans and nonhuman primates, while RESTV infection in humans is probably subclinical, yet it causes highly lethal VHF in macaques [2,3]. Considering the social impact of ebolaviruses, it is important to understand the endemic and epizootic status of RESTV in the Philippines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
