scholarly journals In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy

EBioMedicine ◽  
2019 ◽  
Vol 44 ◽  
pp. 516-529 ◽  
Author(s):  
Vidyleison N. Camargos ◽  
Giselle Foureaux ◽  
Daniel C. Medeiros ◽  
Vivian T. da Silveira ◽  
Celso M. Queiroz-Junior ◽  
...  
Keyword(s):  
Peptide Therapy ◽  
Antibody Dependent Enhancement ◽  
Congenital Zika Syndrome ◽  
Antiviral Peptide ◽  
Immunocompetent Mice

Assembly of HIV-1 gag-proteins: A new target for antiviral peptide therapy?

Peptides 1992 ◽  
1993 ◽  
pp. 133-135 ◽  
Author(s):  
Susanne Modrow ◽  
A. v. Poblotzki ◽  
R. Wagner ◽  
H. R. Gelderblom ◽  
G. Pauli ◽  
...  
Keyword(s):  
Peptide Therapy ◽  
Gag Proteins ◽  
Antiviral Peptide ◽  
Hiv 1

scholarly journals Generation and Characterization of a Mouse-Adapted Makona Variant of Ebola Virus

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 987 ◽  
Author(s):  
Mable Chan ◽  
Anders Leung ◽  
Bryan D. Griffin ◽  
Robert Vendramelli ◽  
Nikesh Tailor ◽  
...  
Keyword(s):  
Mouse Model ◽  
Reverse Genetics ◽  
Ebola Virus ◽  
Lethal Dose ◽  
West African ◽  
Zoonotic Pathogen ◽  
Immunocompetent Mice ◽  
Pro Inflammatory Cytokines ◽  
Prior Adaptation

Ebola virus (EBOV) is a zoonotic pathogen that poses a significant threat to public health, causing sporadic yet devastating outbreaks that have the potential to spread worldwide, as demonstrated during the 2013–2016 West African outbreak. Mouse models of infection are important tools for the development of therapeutics and vaccines. Exposure of immunocompetent mice to clinical isolates of EBOV is nonlethal; consequently, EBOV requires prior adaptation in mice to cause lethal disease. Until now, the only immunocompetent EBOV mouse model was based on the Mayinga variant, which was isolated in 1976. Here, we generated a novel mouse-adapted (MA)-EBOV based on the 2014 Makona isolate by inserting EBOV/Mayinga-MA mutations into the EBOV/Makona genome, followed by serial passaging of the rescued virus in suckling mice. The resulting EBOV/Makona-MA causes lethal disease in adult immunocompetent mice within 6 to 9 days and has a lethal dose (LD50) of 0.004 plaque forming units (PFU). Two additional mutations emerged after mouse-adaptation in the viral nucleoprotein (NP) and membrane-associated protein VP24. Using reverse genetics, we found the VP24 mutation to be critical for EBOV/Makona-MA virulence. EBOV/Makona-MA infected mice that presented with viremia, high viral burden in organs, increased release of pro-inflammatory cytokines/chemokines, and lymphopenia. Our mouse model will help advance pre-clinical development of countermeasures against contemporary EBOV variants.

scholarly journals Characterization of Transmission of Pneumocystis carinii f. sp. muris through Immunocompetent BALB/c Mice

2003 ◽  
Vol 71 (7) ◽  
pp. 3852-3856 ◽  
Author(s):  
F. Gigliotti ◽  
A. G. Harmsen ◽  
T. W. Wright
Keyword(s):  
Pneumocystis Carinii ◽  
Opportunistic Pathogen ◽  
Lung Compliance ◽  
Scid Mice ◽  
Symptomatic Infection ◽  
Normal Host ◽  
Active Replication ◽  
Immunocompetent Mice ◽  
Dynamic Lung Compliance

ABSTRACT By using mouse models, it has been shown that Pneumocystis carinii f. sp. muris can be transmitted to immunocompetent mice that are exposed to immunosuppressed mice with active P. carinii pneumonia. We sought to determine whether P. carinii f. sp. muris could be transmitted between normal mice. The rationale for these experiments was to demonstrate whether the normal host could serve as the reservoir of organisms that produce Pcp when the organism is acquired by the immunosuppressed host. Under the conditions of these experiments, normal mice are able to be infected by brief cohousing with P. carinii-infected SCID mice. There was active replication of organisms in the normal host such that the organism could be transmitted to other normal mice, again with active replication. Mice that had seroconverted after exposure to P. carinii-infected SCID mice were more resistant to infection when reexposed. Infection in normal mice was well tolerated with minimal effects on dynamic lung compliance. We speculate, based on these results, that transmission from normal host to normal host, as an asymptomatic or minimally symptomatic infection, could be a way to maintain this opportunistic pathogen in the environment.

Characterization of Visual Pathway Abnormalities in Infants With Congenital Zika Syndrome Using Computed Tomography and Magnetic Resonance Imaging

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Amanda D. Henderson ◽  
Camila V. Ventura ◽  
Thierry A. G. M. Huisman ◽  
Avner Meoded ◽  
Adriano N. Hazin ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Computed Tomography ◽  
Magnetic Resonance ◽  
Visual Pathway ◽  
Resonance Imaging ◽  
Congenital Zika Syndrome

scholarly journals Characterization of the contemporary Zika virus in immunocompetent mice

2016 ◽  
Vol 12 (12) ◽  
pp. 3107-3109 ◽  
Author(s):  
Na-Na Zhang ◽  
Min Tian ◽  
Yong-Qiang Deng ◽  
Jia-Nan Hao ◽  
Hong-Jiang Wang ◽  
...  
Keyword(s):  
Zika Virus ◽  
Immunocompetent Mice

scholarly journals Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection

2021 ◽  
Vol 102 (9) ◽  
Author(s):  
Constantina Borg ◽  
Aminu S. Jahun ◽  
Lucy Thorne ◽  
Frédéric Sorgeloos ◽  
Dalan Bailey ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Persistent Infection ◽  
Reverse Genetics ◽  
Viral Fitness ◽  
Murine Norovirus ◽  
Viral Loads ◽  
Immunocompetent Mice

Murine norovirus (MNV) is widely used as a model for studying norovirus biology. While MNV isolates vary in their pathogenesis, infection of immunocompetent mice mostly results in persistent infection. The ability of a virus to establish a persistent infection is dependent on its ability to subvert or avoid the host immune response. Previously, we described the identification and characterization of virulence factor 1 (VF1) in MNV, and demonstrated its role as an innate immune antagonist. Here, we explore the role of VF1 during persistent MNV infection in an immunocompetent host. Using reverse genetics, we generated MNV-3 viruses carrying a single or a triple termination codon inserted in the VF1 ORF. VF1-deleted MNV-3 replicated to comparable levels to the wildtype virus in tissue culture. Comparative studies between MNV-3 and an acute MNV-1 strain show that MNV-3 VF1 exerts the same functions as MNV-1 VF1, but with reduced potency. C57BL/6 mice infected with VF1-deleted MNV-3 showed significantly reduced replication kinetics during the acute phase of the infection, but viral loads rapidly reached the levels seen in mice infected with wildtype virus after phenotypic restoration of VF1 expression. Infection with an MNV-3 mutant that had three termination codons inserted into VF1, in which reversion was suppressed, resulted in consistently lower replication throughout a 3 month persistent infection in mice, suggesting a role for VF1 in viral fitness in vivo. Our results indicate that VF1 expressed by a persistent strain of MNV also functions to antagonize the innate response to infection. We found that VF1 is not essential for viral persistence, but instead contributes to viral fitness in mice. These data fit with the hypothesis that noroviruses utilize multiple mechanisms to avoid and/or control the host response to infection and that VF1 is just one component of this.

scholarly journals Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

2009 ◽  
Vol 83 (13) ◽  
pp. 6404-6415 ◽  
Author(s):  
Kelly L. Warfield ◽  
Steven B. Bradfute ◽  
Jay Wells ◽  
Loreen Lofts ◽  
Meagan T. Cooper ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hemorrhagic Fever ◽  
Sampling Studies ◽  
Time To Death ◽  
Adult Mice ◽  
Serial Sampling ◽  
Liver Homogenates ◽  
Immunocompetent Mice ◽  
Spleen And Lymph Nodes

ABSTRACT The lack of a mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV), and has created a bottleneck in the development of antiviral therapeutics. Primary isolates of the filoviruses, i.e., ebolavirus (EBOV) and MARV, are not lethal to immunocompetent adult mice. Previously, pathological, virologic, and immunologic evaluation of a mouse-adapted EBOV, developed by sequential passages in suckling mice, identified many similarities between this model and EBOV infections in nonhuman primates. We recently demonstrated that serially passaging virus recovered from the liver homogenates of MARV-infected immunodeficient (SCID) mice was highly successful in reducing the time to death in these mice from 50 to 70 days to 7 to 10 days after challenge with the isolate MARV-Ci67, -Musoke, or -Ravn. In this study, we extended our findings to show that further sequential passages of MARV-Ravn in immunocompetent mice caused the MARV to kill BALB/c mice. Serial sampling studies to characterize the pathology of mouse-adapted MARV-Ravn revealed that this model is similar to the guinea pig and nonhuman primate MHF models. Infection of BALB/c mice with mouse-adapted MARV-Ravn caused uncontrolled viremia and high viral titers in the liver, spleen, lymph node, and other organs; profound lymphopenia; destruction of lymphocytes within the spleen and lymph nodes; and marked liver damage and thrombocytopenia. Sequencing the mouse-adapted MARV-Ravn strain revealed differences in 16 predicted amino acids from the progenitor virus, although the exact changes required for adaptation are unclear at this time. This mouse-adapted MARV strain can now be used to develop and evaluate novel vaccines and therapeutics and may also help to provide a better understanding of the virulence factors associated with MARV.

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