A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

Abstract

Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

Post-exposure treatments for Ebola and Marburg virus infections

“…Small animals including mice, hamsters and guinea pigs have been used as animal models of filovirus haemorrhagic fever [226][227][228][229][230][231][232][233][234] . Mice and guinea pigs were historically used to screen post-exposure interventions against filoviruses, but these models have often failed to predict efficacy of candidate therapies in the more robust non-human primate (NHP) models 8,9 .…”

丝状病毒感染的动物模型

“… Marzi et al ( 2016 ) recently developed a novel Syrian golden hamster model for MARV infection using a hamster-adapted MARV variant Angola (HA-MARV). This model provides new insight on virus pathogenesis in hamsters, and moreover closely resembles MARV infection in humans and NHPs, including hemorrhagic manifestations and coagulation abnormalities.…”

“…Animal models against filoviruses have been developed in mice, guinea pigs, hamsters, ferrets and NHPs ( Bente et al, 2009 ; Bradfute et al, 2012 ; Connolly et al, 1999 ; Marzi et al, 2016 ; Kozak et al, 2016 ; Kroeker et al, 2017b ; Yamaoka et al, 2017 ). The development of animal models that recapitulates hallmarks of human filoviral disease is crucial in understanding the pathogenesis of these viruses.…”

Filovirus Strategies to Escape Antiviral Responses

“…Antigen-presenting cells, including monocytes, macrophages, and myeloid dendritic cells, are considered the primary target cells of filoviruses and play crucial roles in filovirus pathogenesis (Bray and Geisbert 2005;Martinez et al 2012). Infection of these cells by filoviruses severely impacts their function in mediating an appropriate innate immune response and might play a role in the excessive pro-inflammatory response observed during filovirus disease (Geisbert et al 2003a, c;Hensley et al 2002;Leroy et al 2001;Rubins et al 2007;Baize et al 2002;Wauquier et al 2010;Ruibal et al 2016;Rougeron et al 2015;Feldmann and Geisbert 2011;Villinger et al 1999;McElroy et al 2016;Gupta et al 2001;McElroy et al 2014a, b;Sanchez et al 2004;Hutchinson and Rollin 2007;Ignatiev et al 2000;Ebihara et al 2011;Marzi et al 2013;Martins et al 2015;van Paassen et al 2012;Fritz et al 2008;Hensley et al 2011;Alves et al 2010;Geisbert et al 2007;Lin et al 2015;Connor et al 2015;Fernando et al 2015;Ignat'ev et al 1995;Caballero et al 2014Caballero et al , 2016Marzi et al 2016). In addition, comparative data on the cytokine and chemokine responses in EBOV-infected patients and nonhuman primates suggest that a broadly dysregulated inflammatory response is associated with severe or fatal EBOV disease (Baize et al 1999(Baize et al , 2002McElroy et al 2014a;…”