Molecular pathogenesis of viral hemorrhagic fever

Abstract

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

“…Some viruses are known to activate the coagulation cascade, mainly by promoting tissue factor on endothelial cells (HSV and Dengue virus) as well as on lymphoid macrophages and circulating blood cells (Ebola virus) [32]. Clinical manifestations with Dengue and Ebola viruses are disseminated intravascular coagulation with an hemorrhagic pattern [33]. Our patients with COVID-19 had no such phenotype but were highly thrombotic without evidence of DIC.…”

When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses

“…Moreover, DCs are early and sustained targets of EBOV that can disseminate infection from the portals of viral entry to the regional lymph nodes, spleen, and liver [11]. Since Siglec-1 is expressed in all these EBOV replicating-tissues [23,156], this receptor could also boost systemic viral spread as previously suggested for HIV-1 [11,13,139,157,158]. Collectively, these data indicate that Siglec-1 on DCs may not only participate in viral transmission at the mucosa, but also promote systemic viral dissemination to secondary lymphoid tissues.…”

Cytokine storms in infectious diseases

“…The aberrant inflammatory response that accompanies Ebola virus infection, termed viral hemorrhagic fever (VHF), can be caused by multiple RNA viruses, including arenaviruses, bunyaviruses, filoviruses, and flaviviruses. Basler reviews the linkages between excessive inflammatory responses, hemorrhage and disseminated intravascular coagulation in the pathological manifestation of VHF in humans and non-human primates [13]. The review highlights potential sources of inflammatory cytokines during multiple VHF infections and points out that while dendritic cells are targets of viral replication by multiple VHF viruses, these cells secrete minimal amounts of cytokines/chemokines while monocytes and macrophages appear to be significant sources of inflammatory cytokines during these infections.…”