Molecular Evasion and Immune Responses to Ebola Virus- an Approach to Ebola Evasion Mechanism and Immunotherapeutic

Abstract

Ebola virus (EBOV; species Zaire ebolavirus, family Filoviridae) causes Ebola virus disease (EVD), a severe hemorrhagic fever of humans and non-human primates with case fatality rates that have ranged from 25% to 90% in past outbreaks. The 2013–2016 West African epidemic — more than 28,600 cases and 11,325 deaths — transformed EVD from a neglected zoonosis into a test case for modern vaccinology, immunotherapeutics and outbreak science. This review integrates current understanding of the molecular biology of EBOV with the host immune response it provokes. We describe the 18.9-kb negative-sense RNA genome and its seven genes; the architecture of the filamentous virion; and the replication cycle, from glycoprotein-mediated attachment and Niemann–Pick C1–dependent endosomal fusion to VP40-driven assembly and budding. We then examine the virus's multi-layered interference with innate immunity — VP35-mediated blockade of interferon induction, VP24-mediated blockade of interferon signaling, and glycoprotein-based shielding, decoy and counter-tetherin strategies — and show how these mechanisms shape the systemic immunopathology of EVD: abrupt activation of monocytes and macrophages, a dysregulated "cytokine storm", bystander lymphocyte apoptosis, dendritic-cell failure, coagulopathy and vascular leakage. Correlates of survival — early humoral responses, controlled inflammation and timely T-cell immunity — are contrasted with the signatures of fatal disease. Finally, we review the countermeasure landscape built on this knowledge: the rVSV-vectored vaccine Ervebo, the Ad26/MVA-BN-Filo regimen, the monoclonal-antibody therapeutics ansuvimab (mAb114) and REGN-EB3 validated in the PALM randomized trial, and the remaining gaps for Sudan, Bundibugyo and other ebolaviruses — thrown into sharp relief by the 2025–2026 outbreaks in the Democratic Republic of the Congo. Understanding the molecular dialogue between EBOV and the immune system remains the foundation for the next generation of pan-filovirus vaccines and therapeutics.