Camouflage and misdirection: the full-on assault of ebola virus disease

Abstract

Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and nonhuman primates. Ebola protein interactions with host cellular proteins disrupt type I and type II interferon responses, RNAi antiviral responses, antigen presentation, T-cell-dependent B cell responses, humoral antibodies, and cell-mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and "cytokine storm" that is characteristic of fatal ebolavirus infection. Here, we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade antiviral defenses.

Figure 1

Ebolavirus life cycle: (Left) Virus particles attach to cell surface, inducing macropinocytosis and virus uptake, possibly using apoptotic mimicry to suppress inflammatory responses. The particle is brought to a low pH compartment where it is cleaved by cysteine proteases to reveal its NPC1 receptor binding domain (RBD). Following fusion and uncoating, the viral genome is transcribed into mRNA and viral proteins produced. Eventually, a signal to begin genome replication occurs, followed by particle assembly and budding. Immune avoidance mechanisms: Expression and secretion of sGP serves as an antibody decoy for antibodies generated against GP. Viral proteins VP35, VP30 and VP24 are expressed and mediate innate immune avoidance in all cell types. (Left) VP35 interferes with RIG-I/MDA-5 signaling and induction of interferon. Additionally, VP35 and VP30 block the RNAi response against viral gene expression. (Right) VP24 acts to inhibit Type I and II interferon (IFN) signaling. This prevents interferon-induced gene expression and in antigen presenting cells blocks enhancement of antigen presentation to T cells.