Chapter Nineteen. Infection And Ecology: Calomys Callosus, Machupo Virus, and Acute Hemorrhagic Fever

2010 ◽  
pp. 404-422
Author(s):  
Karl M. Johnson
Keyword(s):  
Hemorrhagic Fever ◽  
Calomys Callosus ◽  
Machupo Virus

Immune Tolerance in Calomys callosus infected with Machupo Virus

Nature ◽  
1969 ◽  
Vol 222 (5198) ◽  
pp. 1090-1091 ◽  
Author(s):  
GUSTAVO JUSTINES ◽  
KARL M. JOHNSON
Keyword(s):  
Immune Tolerance ◽  
Calomys Callosus ◽  
Machupo Virus

scholarly journals Machupo Virus Expressing GPC of the Candid#1 Vaccine Strain of Junin Virus Is Highly Attenuated and Immunogenic

2015 ◽  
Vol 90 (3) ◽  
pp. 1290-1297 ◽  
Author(s):  
Takaaki Koma ◽  
Michael Patterson ◽  
Cheng Huang ◽  
Alexey V. Seregin ◽  
Payal D. Maharaj ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vaccine Strain ◽  
Causative Agent ◽  
Transmembrane Domain ◽  
Hemorrhagic Fever ◽  
Single Amino Acid ◽  
Junin Virus ◽  
Machupo Virus ◽  
Junín Virus

ABSTRACTMachupo virus (MACV) is the causative agent of Bolivian hemorrhagic fever. Our previous study demonstrated that a MACV strain with a single amino acid substitution (F438I) in the transmembrane domain of glycoprotein is attenuated but genetically unstable in mice. MACV is closely related to Junin virus (JUNV), the causative agent of Argentine hemorrhagic fever. Others and our group have identified the glycoprotein to be the major viral factor determining JUNV attenuation. In this study, we tested the compatibility of the glycoprotein of the Candid#1 live-attenuated vaccine strain of JUNV in MACV replication and its ability to attenuate MACVin vivo. Recombinant MACV with the Candid#1 glycoprotein (rMACV/Cd#1-GPC) exhibited growth properties similar to those of Candid#1 and was genetically stablein vitro. In a mouse model of lethal infection, rMACV/Cd#1-GPC was fully attenuated, more immunogenic than Candid#1, and fully protective against MACV infection. Therefore, the MACV strain expressing the glycoprotein of Candid#1 is safe, genetically stable, and highly protective against MACV infection in a mouse model.IMPORTANCECurrently, there are no FDA-approved vaccines and/or treatments for Bolivian hemorrhagic fever, which is a fatal human disease caused by MACV. The development of antiviral strategies to combat viral hemorrhagic fevers, including Bolivian hemorrhagic fever, is one of the top priorities of the Implementation Plan of the U.S. Department of Health and Human Services Public Health Emergency Medical Countermeasures Enterprise. Here, we demonstrate for the first time that MACV expressing glycoprotein of Candid#1 is a safe, genetically stable, highly immunogenic, and protective vaccine candidate against Bolivian hemorrhagic fever.

Some Characteristics of Machupo Virus, Causative Agent of Bolivian Hemorrhagic Fever

1967 ◽  
Vol 16 (4) ◽  
pp. 531-538 ◽  
Author(s):  
P. A. Webb ◽  
M. L. Kuns ◽  
K. M. Johnson ◽  
R. B. Mackenzie
Keyword(s):  
Causative Agent ◽  
Hemorrhagic Fever ◽  
Machupo Virus

Isolation of Machupo Virus from Wild Rodent Calomys callosus

1966 ◽  
Vol 15 (1) ◽  
pp. 103-106 ◽  
Author(s):  
K. M. Johnson ◽  
P. A. Webb ◽  
R. B. Mackenzie ◽  
C. E. Yunker ◽  
M. L. Kuns
Keyword(s):  
Wild Rodent ◽  
Calomys Callosus ◽  
Machupo Virus

scholarly journals Machupo virus with mutations in the transmembrane domain and glycosylation sites is attenuated and immunogenic in animal models of Bolivian Hemorrhagic Fever

2021 ◽  
Author(s):  
Emily K Mantlo ◽  
Junki Maruyama ◽  
John T Manning ◽  
Timothy G Wanninger ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Animal Models ◽  
Mouse Model ◽  
Guinea Pigs ◽  
Rational Design ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Hemorrhagic Fever ◽  
Highly Pathogenic ◽  
Glycosylation Sites ◽  
Machupo Virus

AbstractSeveral highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans, for which vaccines and antivirals are limited or unavailable. New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuate MACV in an IFN-αβ/γ receptor knockout mouse model. However, some capability to induce neurological pathology still remained. Highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. A F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in GPC TMD. The MACV mutant is fully attenuated in IFN-αβ/γ receptor knockout mice and outbred guinea pigs. Furthermore, inoculation with this mutant MACV fully protected guinea pigs from wild-type MACV lethal challenge. Lastly, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which informs the rational design of potential vaccine candidates for highly pathogenic arenaviruses.ImportanceFor arenaviruses, the only vaccine available is the live-attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. Nevertheless, mutating either of them is not sufficient for full and stable attenuation of JUNV. Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC, and also introduced the corresponding F438I substitution in the GPC TMD. This MACV mutant is fully attenuated in two animal models and protects animals from lethal infection. Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism.

scholarly journals Validation of Сhoice of Laboratory Model for Preclinical Estimation of Medical Protectors Against Bolivian Hemorrhagic Fever

2019 ◽  
Vol 3 (4) ◽  
pp. 319-328
Keyword(s):  
Animal Models ◽  
Guinea Pigs ◽  
Macaca Fascicularis ◽  
Hemorrhagic Fever ◽  
Laboratory Animals ◽  
Laboratory Model ◽  
Small Laboratory ◽  
Quantitative Indices ◽  
Machupo Virus

Th is review is dedicated to the peculiarities of pathogenesis of the experimental Bolivian hemorrhagic fever (BHF) – the disease, caused by Machupo virus (Arenaviridae family). Th e authors come to the conclusion that for carrying out preclinical researches of the medical means of protection (MMP) in vivo on small laboratory animals it is expedient to use guinea pigs, infected with a strain of Chicava or with a variant of Carvallo strain, adapted for these animals. Th e use of guinea pigs as small laboratory animals when studying pathogenesis of the disease caused by Machupo virus allows to carry out statistically reliable defi nition of quantitative indices of an experimental infection and to select medicines for the fi nal stage of preclinical assessment. As arenaviruses block the process of formation of interferon (IFN) in the infected organism, mice, defective by IFN formation, are the perspective animal models for the study of BHF pathogenesis and may be used for the study of attenuated variants of Machupo virus. Th e Javanese macaques (Macaca fascicularis) are the laboratory animals, modeling the pathogenetic manifestations of BHF in humans. Th ey can be used when carrying out the fi nal stages of preclinical assessment of means of medical protection

Organisms of Concern But Not Foodborne or Confirmed Foodborne: Bolivian Hemorrhagic Fever Virus (Machupo Virus)

2019 ◽  
Author(s):  
Alfonso J. Rodriguez-Morales ◽  
Diana M. Castañeda-Hernández ◽  
Juan Pablo Escalera-Antezana ◽  
Lucia Elena Alvarado-Arnez
Keyword(s):  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Hemorrhagic Fever Virus ◽  
Machupo Virus

scholarly journals Unusual Molecular Architecture of the Machupo Virus Attachment Glycoprotein

2009 ◽  
Vol 83 (16) ◽  
pp. 8259-8265 ◽  
Author(s):  
Thomas A. Bowden ◽  
Max Crispin ◽  
Stephen C. Graham ◽  
David J. Harvey ◽  
Jonathan M. Grimes ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
New World ◽  
Hemorrhagic Fever ◽  
Affinity Binding ◽  
Protein Fold ◽  
Molecular Architecture ◽  
Viral Attachment ◽  
Virus Attachment ◽  
High Affinity ◽  
Machupo Virus

ABSTRACT New World arenaviruses, which cause severe hemorrhagic fever, rely upon their envelope glycoproteins for attachment and fusion into their host cell. Here we present the crystal structure of the Machupo virus GP1 attachment glycoprotein, which is responsible for high-affinity binding at the cell surface to the transferrin receptor. This first structure of an arenavirus glycoprotein shows that GP1 consists of a novel α/β fold. This provides a blueprint of the New World arenavirus attachment glycoproteins and reveals a new architecture of viral attachment, using a protein fold of unknown origins.

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