Early immune responses accompanying human asymptomatic Ebola infections

Abstract

SUMMARYIn a recent study we identified certain asymptomatic individuals infected by Ebola virus (EBOV) who mounted specific IgG and early and strong inflammatory responses. Here, we further characterized the primary immune response to EBOV during the course of asymptomatic infection in humans. Inflammatory responses occurred in temporal association with anti-inflammatory phase composed by soluble antagonist IL-1RA, circulating TNF receptors, IL-10 and cortisol. At the end of the inflammatory process, mRNA expression of T-cell cytokines (IL-2 and IL-4) and activation markers (CD28, CD40L and CTLA4) was up-regulated, strongly suggesting T-cell activation. This T-cell activation was followed by EBOV-specific IgG responses (mainly IgG3 ang IgG1), and by marked and sustained up-regulation of IFNg, FasL and perforin mRNA expression, suggesting activation of cytotoxic cells. The terminal down-regulation of these latter markers coincided with the release of the apoptotic marker 41/7 NMP in blood and with the disappearance of viral RNA from PBMC, suggesting that infected cells are eliminated by cytotoxic mechanisms. Finally, RT-PCR analysis of TCR-Vb repertoire usage showed that TCR-Vb12 mRNA was never expressed during the infection. Taken together, these findings improve our understanding about immune response during human asymptomatic Ebola infection, and throw new light on protection against Ebola virus.

Ebola virus-like particles protect from lethal Ebola virus infection

“…EBOV infection has been associated with massive release of inflammatory chemokines and cytokines late in the course of disease (40)(41)(42)(43)(44)(45), either as a cause or effect of pathogenic events. Considering the morphologic similarity of eVLPs to the live virus, serum cytokines were tested at 6 h and 1, 3, 5, 7, 10, 14, and 21 days postvaccination to determine whether eVLPs also induced systemic cytokine release.…”

Ebola Virus Does Not Block Apoptotic Signaling Pathways

“…Lymphocytes remain uninfected by EBOV, but a decrease in lymphocyte numbers due to bystander apoptosis is observed during EBOV infection (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Increased expression levels of inducers of apoptosis, including the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL), have been observed during EBOV infection and might play a role in the observed bystander lymphocyte apoptosis (3,9,10,(13)(14)(15). Only limited and contradictory data are available about apoptosis of EBOV-infected cells (7,8,10,16).…”

Aerosol Exposure to the Angola Strain of Marburg Virus Causes Lethal Viral Hemorrhagic Fever in Cynomolgus Macaques

“…For example, patients who recover from EBOV-Zaire infection develop an early immune response involving specific humoral factors and a tightly regulated cytotoxic T-lymphocyte response. 53 However, fatal outcome has been associated with suboptimum humoral immunity, unregulated T-cell activation, lymphocyte apoptosis, and uncontrolled mononuclear phagocyte activation resulting in elevated cytokine levels that contribute to the multisystemic dysfunction seen terminally. 4,86 Autopsy studies of EBOV and MARV cases are limited 24,26,67,93 in large part because of the difficulty of performing autopsies in isolated areas where these cases occur and because of the biosafety concerns of performing such autopsies.…”