Faculty Opinions recommendation of Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model.

Author(s):  
Wade Blair
2014 ◽  
Vol 105 ◽  
pp. 17-21 ◽  
Author(s):  
Lisa Oestereich ◽  
Anja Lüdtke ◽  
Stephanie Wurr ◽  
Toni Rieger ◽  
César Muñoz-Fontela ◽  
...  

2016 ◽  
Vol 90 (20) ◽  
pp. 9209-9223 ◽  
Author(s):  
Robert Kozak ◽  
Shihua He ◽  
Andrea Kroeker ◽  
Marc-Antoine de La Vega ◽  
Jonathan Audet ◽  
...  

ABSTRACTBundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the orderMononegavirales. To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals.IMPORTANCEThe 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genusEbolavirusand has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such a model for BDBV is crucial to evaluating vaccines and therapies and potentially understanding transmission. To address this, we demonstrated that ferrets are susceptible models to BDBV infection as well as to Ebola virus infection and that no virus adaptation is required. Moreover, these animals develop a disease that is similar to that seen in humans and nonhuman primates. We believe that this will improve the ability to study BDBV and provide a platform to test vaccines and therapeutics.


2017 ◽  
pp. JVI.01693-17 ◽  
Author(s):  
Kiyoko Iwatsuki-Horimoto ◽  
Noriko Nakajima ◽  
Yurie Ichiko ◽  
Yuko Sakai-Tagawa ◽  
Takeshi Noda ◽  
...  

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using them as an alternative animal model to mice. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a pdm09 and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were airborne transmissible in these hamsters. Hamsters thus have potential as a small animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as H1N1 virus transmission studies.IMPORTANCEWe found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested are airborne transmitted in these hamsters. Syrian hamsters thus have potential as a small animal model for the study of human influenza viruses.


2012 ◽  
Vol 5 ◽  
pp. IDRT.S10652
Author(s):  
Takashi Irie ◽  
Elena Carnero ◽  
Adolfo García-Sastre ◽  
Ronald N. Harty

The M40 VSV recombinant was engineered to contain overlapping PTAP and PPxY L-domain motifs and flanking residues from the VP40 protein of Ebola virus. Replication of M40 in cell culture is virtually indistinguishable from that of control viruses. However, the presence of the Ebola PTAP motif in the M40 recombinant enabled this virus to interact with and recruit host Tsg101, which was packaged into M40 virions. In this brief report, we compared replication and the pathogenic profiles of M40 and the parental virus M51R in mice to determine whether the presence of the Ebola L-domains and flanking residues altered in vivo characteristics of the virus. Overall, the in vivo characteristics of M40 were similar to those of the parental M51R virus, indicating that the Ebola sequences did not alter pathogenesis of VSV in this small animal model of infection.


2001 ◽  
Vol 82 (9) ◽  
pp. 2125-2129 ◽  
Author(s):  
Alexey Evlashev ◽  
Hélène Valentin ◽  
Pierre Rivailler ◽  
Olga Azocar ◽  
Chantal Rabourdin-Combe ◽  
...  

Analysis of measles virus (MV) pathogenesis requires the development of an adequate small animal model of MV infection. In this study, permissivity to MV infection was compared in human and transgenic murine T lymphocytes, expressing different levels of the human MV receptor, CD46. Whereas MV binding and entry correlated with CD46 expression, higher levels of MV replication were always observed in human T lymphocytes. This suggests the existence of intracellular factors, acting posterior to virus entry, that could limit MV replication in murine lymphocytes and should be considered when creating new animal models of MV infection.


2010 ◽  
Vol 15 (4) ◽  
pp. 661-675 ◽  
Author(s):  
Megan M McCausland ◽  
Mohammed Rafii-El-Idrissi Benhnia ◽  
Lindsay Crickard ◽  
John Laudenslager ◽  
Steven W Granger ◽  
...  

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