New Insights Into Marburg Virus Disease Pathogenesis in the Rhesus Macaque Model

Ebola virus (EBOV) is a negative-sense RNA virus that can infect humans and nonhuman primates with severe health consequences. Development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. The goal of this study was to further characterize EBOV disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. Rhesus macaques were intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger-to-treat” for use in therapeutic studies.

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Combination therapy protects macaques against advanced Marburg virus disease

Nature Communications ◽

10.1038/s41467-021-22132-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Robert W. Cross ◽

Zachary A. Bornholdt ◽

Abhishek N. Prasad ◽

Viktoriya Borisevich ◽

Krystle N. Agans ◽

...

Keyword(s):

Combination Therapy ◽

Rhesus Monkeys ◽

Viral Infections ◽

Virus Disease ◽

Marburg Virus ◽

Therapeutic Window ◽

Post Inoculation ◽

Primate Model ◽

Lethal Infection ◽

Human Primate

AbstractMonoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.

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Fractal Dimensions of Subviral Particle Movement

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2018-0020 ◽

2018 ◽

Vol 4 (1) ◽

pp. 79-82 ◽

Cited By ~ 1

Author(s):

Andreas Rausch ◽

Thomas Schanze

Keyword(s):

Virus Disease ◽

Fractal Dimensions ◽

Real Data ◽

Marburg Virus ◽

Virus Infections ◽

Fluorescence Image ◽

Good Potential ◽

Infected Cells ◽

Subviral Particle ◽

Subviral Particles

AbstractThe development of new medicines against virus infections like the Marburg virus disease requires an accurate knowledge of the respective pathogens. Conventionally, this process is very time expensive. In cooperation with the Virology of the Philipps-University in Marburg an automatic tracking algorithm for subviral particles in fluorescence image sequences was developed and programmed. To expand the benefit for the pharmaceutical researchers, also the trackevaluations need to be widely automated. In this work, a new parameterizing-method facing the fractal dimensions of spline interpolated subviral particle tracks is presented and tested with simulated and real data. The results reveal a good potential to classify tracks and, thus, types of subviral particles in infected cells.

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Clinical Documentation and Data Transfer from Ebola and Marburg Virus Disease Wards in Outbreak Settings: Health Care Workers’ Experiences and Preferences

Viruses ◽

10.3390/v6020927 ◽

2014 ◽

Vol 6 (2) ◽

pp. 927-937 ◽

Cited By ~ 12

Author(s):

Silja Bühler ◽

Paul Roddy ◽

Ellen Nolte ◽

Matthias Borchert

Keyword(s):

Health Care ◽

Health Care Workers ◽

Data Transfer ◽

Virus Disease ◽

Marburg Virus ◽

Clinical Documentation ◽

Care Workers

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Defining HIV/SIV Particle Localization and Infection after Rectal Challenge in the Rhesus Macaque Model using Reporter Systems

AIDS Research and Human Retroviruses ◽

10.1089/aid.2014.5387.abstract ◽

2014 ◽

Vol 30 (S1) ◽

pp. A181-A182

Author(s):

Wesley A. Grimm ◽

Luis Barcena ◽

Danijela Maric ◽

Gianguido C. Cianci ◽

Daniel Stieh ◽

...

Keyword(s):

Rhesus Macaque ◽

Macaque Model ◽

Reporter Systems ◽

Particle Localization

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Comparative Pathogenesis of Epidemic and Enzootic Chikungunya Viruses in a Pregnant Rhesus Macaque Model

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.2010.10-0290 ◽

2010 ◽

Vol 83 (6) ◽

pp. 1249-1258 ◽

Cited By ~ 44

Author(s):

Ching-I Chen ◽

William K. Reisen ◽

Aaron C. Brault ◽

Patricia Pesavento ◽

David C. Clark ◽

...

Keyword(s):

Rhesus Macaque ◽

Macaque Model

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Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

Journal of Diabetes Research ◽

10.1155/2017/3601708 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10

Author(s):

Tingfu Du ◽

Shuaiyao Lu ◽

Qinfang Jiang ◽

Yun Li ◽

Kaili Ma

Keyword(s):

Rhesus Macaque ◽

Differentially Expressed ◽

Hepatic Tissue ◽

Expression Change ◽

Macaque Model ◽

Genome Wide ◽

Proteomic Study ◽

Pathway Analyses ◽

High Sucrose

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ-) induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

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