scholarly journals Idiopathic Chronic Diarrhea in Rhesus Macaques Is Not Associated with Enteric Viral Infections

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2503
Author(s):  
Eric Delwart ◽  
Michael J. Tisza ◽  
Eda Altan ◽  
Yanpeng Li ◽  
Xutao Deng ◽  
...  
Keyword(s):  
Late Stage ◽  
Viral Infections ◽  
Chronic Diarrhea ◽  
Rhesus Macaques ◽  
Viral Metagenomics ◽  
Primate Research ◽  
Healthy Controls ◽  
Viral Loads ◽  
Common Causes ◽  
Human Primate

While recent changes in treatment have reduced the lethality of idiopathic chronic diarrhea (ICD), this condition remains one of the most common causes of rhesus macaque deaths in non-human primate research centers. We compared the viromes in fecal swabs from 52 animals with late stage ICD and 41 healthy animals. Viral metagenomics targeting virus-like particles was used to identify viruses fecally shed by each animal. Five viruses belonging to the Picornaviridae, one to the Caliciviridae, one to the Parvoviridae, and one to the Adenoviridae families were identified. The fraction of reads matching each viral species was then used to estimate and compare viral loads in ICD cases versus healthy controls. None of the viruses detected in fecal swabs were strongly associated with ICD.

scholarly journals Idiopathic chronic diarrhea in rhesus macaques is not associated with enteric viral infections

2021 ◽  
Author(s):  
Eric Delwart ◽  
Michael J Tisza ◽  
Eda Altan ◽  
Yanpeng Li ◽  
Xutao Deng ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Viral Infections ◽  
Chronic Diarrhea ◽  
Rhesus Macaques ◽  
Viral Metagenomics ◽  
Primate Research ◽  
Healthy Controls ◽  
Viral Loads ◽  
Common Causes ◽  
Human Primate

While recent changes in treatment have reduced the lethality of idiopathic chronic diarrhea (ICD), this condition remains one of the most common causes of rhesus macaque deaths in non-human primate research centers. We compared the eukaryotic viromes in fecal swabs from 52 animals with ICD and 41 healthy animals. Viral metagenomics targeting virus-like particles was used to identify viruses shed by each animal. Five viruses belonging to the Picornaviridae, one to the Caliciviridae, one to the Parvoviridae, and one to the Adenoviridae families were identified. The fraction of reads matching each viral species was then used to estimate and compare viral loads in ICD cases versus healthy controls. None of the eukaryotic viruses detected in fecal swabs were strongly associated with ICD. Other potential causes of ICD are discussed.

scholarly journals Enteric viruses nucleic acids distribution along the digestive tract of rhesus macaques with idiopathic chronic diarrhea

2021 ◽  
Author(s):  
Eric Delwart ◽  
David Merriam ◽  
Amir Ardeshir ◽  
Eda Altan ◽  
Yanpeng Li ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Chronic Diarrhea ◽  
Rhesus Macaques ◽  
Distal Colon ◽  
Viral Metagenomics ◽  
Dna Viruses ◽  
Mucosal Scraping ◽  
Rna And Dna ◽  
Lower Digestive Tract

AbstractIdiopathic chronic diarrhea (ICD) is a common clinical condition in captive rhesus macaques, claiming 33% of medical culls (i.e. deaths unrelated to research). Using viral metagenomics we characterized the eukaryotic virome in digestive tract tissues collected at necropsy from nine animals with ICD. We show the presence of multiple viruses in the Parvoviridae and Picornaviridae family. We then compared the distribution of viral reads in the stomach, duodenum, jejunum, ileum, and the proximal, transverse, and distal colons. Tissues and mucosal scraping from the same locations showed closely related results while different gut tissues from the same animal varied widely. Picornavirus reads were generally more abundant in the lower digestive tract, particularly in the descending (distal) colon. Parvoviruses were more abundant in the upper reach particularly in the stomach. In situ hydridization (ISH) of fixed tissues showed punctuated staining for both these RNA and DNA viruses in the distal colon. Parvovirus ISH staining was also detected in the stomach/duodenum/jejunum in distinct oval-shaped structures. Therefore, the location of enteric viral nucleic acid differed widely between different viral families and along the length of the digestive tract.

scholarly journals Divergent Enteroviruses from Macaques with Chronic Diarrhea

2021 ◽  
Vol 10 (31) ◽  
Author(s):  
Kathie A. Mihindukulasuriya ◽  
Lindsay Droit ◽  
Margaret H. Gilbert ◽  
Peter J. Didier ◽  
Anne Paredes ◽  
...  
Keyword(s):  
Macaca Mulatta ◽  
Chronic Diarrhea ◽  
Rhesus Macaques ◽  
Draft Genome ◽  
Research Center ◽  
Primate Research ◽  
Genome Sequences ◽  
Content Type ◽  
The Family ◽  
National Primate Research

We report the draft genome sequences of five novel members of the family Picornaviridae that were isolated from the stool of rhesus macaques ( Macaca mulatta ) with chronic diarrhea. The strains were named NOLA-1 through NOLA-5 because the macaques were residents of the Tulane National Primate Research Center.

scholarly journals Combination therapy protects macaques against advanced Marburg virus disease

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.

scholarly journals Virome biogeography in the lower gastrointestinal tract of rhesus macaques with chronic diarrhea

Virology ◽  
2019 ◽  
Vol 527 ◽  
pp. 77-88 ◽  
Author(s):  
Guoyan Zhao ◽  
Lindsay Droit ◽  
Margaret H. Gilbert ◽  
Faith R. Schiro ◽  
Peter J. Didier ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Chronic Diarrhea ◽  
Rhesus Macaques ◽  
Lower Gastrointestinal Tract

scholarly journals Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections

2015 ◽  
Vol 22 (9) ◽  
pp. 1025-1032 ◽  
Author(s):  
Per Venge ◽  
Lena Douhan-Håkansson ◽  
Daniel Garwicz ◽  
Christer Peterson ◽  
Shengyuan Xu ◽  
...  
Keyword(s):  
Whole Blood ◽  
Human Neutrophil ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Response Times ◽  
Clinical Performance ◽  
Point Of Care ◽  
Signs And Symptoms ◽  
Healthy Controls ◽  
Acute Infections

ABSTRACTThe distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P< 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P< 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

scholarly journals Viral route of infection determines the effect of Drosophila melanogaster gut bacteria on host resistance and tolerance to disease

2021 ◽  
Author(s):  
Miguel Landum ◽  
Marta Salvado Silva ◽  
Nelson Martins ◽  
Luís Teixeira
Keyword(s):  
Drosophila Melanogaster ◽  
Viral Infections ◽  
Systemic Infection ◽  
Lactobacillus Brevis ◽  
Gut Bacteria ◽  
Associated Bacteria ◽  
Germ Free ◽  
Viral Loads ◽  
Route Of Infection ◽  
The Impact

AbstractThe microbial community interacting with a host can modulate the outcome of pathogenic infections. For instance, Wolbachia, one of the most prevalent invertebrate endosymbionts, strongly increases resistance of Drosophila melanogaster and other insect hosts, to many RNA viruses. D. melanogaster is also in continuous association with gut bacteria, whose role in antiviral immunity is poorly characterized. Here we asked how gut-colonizing bacteria impact viral titres and host survival, and how these interact with route of infection or Wolbachia presence. We compared germ-free flies and flies associated with two gut bacteria species recently isolated from wild flies (Acetobacter thailandicus and Lactobacillus brevis). We found that Wolbachia-conferred protection to both DCV or FHV is not affected by the presence or absence of these gut bacteria. Flies carrying A. thailandicus have lower DCV loads than germ-free flies, upon systemic infection, but reduced survival, indicating that these bacteria increase resistance to virus and decrease disease tolerance. Association with L. brevis, alone or in combination with A. thailandicus, did not lead to changes in survival to systemic infection. In contrast to the effect on systemic infection, we did not observe an impact of these bacteria on survival or viral loads after oral infection. Overall, the impact of gut-associated bacteria in resistance and tolerance to viruses was mild, when compared with Wolbachia. These results indicate that the effect of gut-associated bacteria to different viral infections, and different routes of infection, is complex and understanding it requires a detailed characterization of several parameters of infection.

scholarly journals The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253487
Author(s):  
Conrad E. Z. Chan ◽  
Shirley G. K. Seah ◽  
De Hoe Chye ◽  
Shane Massey ◽  
Maricela Torres ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Neutralizing Antibodies ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Effector Functions ◽  
Viral Loads ◽  
Therapeutic Doses ◽  
Dose Dependent

Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development of SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from a convalescent patient. Antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the SARS-CoV-2 Spike protein. SC31 exhibited potent anti-SARS-CoV-2 activities in multiple animal models. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, treatment with SC31 greatly reduced viral loads and attenuated pro-inflammatory responses linked to the severity of COVID-19. Importantly, a comparison of the efficacies of SC31 and its Fc-null LALA variant revealed that the optimal therapeutic efficacy of SC31 requires Fc-mediated effector functions that promote IFNγ-driven anti-viral immune responses, in addition to its neutralization ability. A dose-dependent efficacy of SC31 was observed down to 5mg/kg when administered before viral-induced lung inflammatory responses. In addition, antibody-dependent enhancement was not observed even when infected mice were treated with SC31 at sub-therapeutic doses. In SARS-CoV-2-infected hamsters, SC31 treatment significantly prevented weight loss, reduced viral loads, and attenuated the histopathology of the lungs. In rhesus macaques, the therapeutic potential of SC31 was evidenced through the reduction of viral loads in both upper and lower respiratory tracts to undetectable levels. Together, the results of our preclinical studies demonstrated the therapeutic efficacy of SC31 in three different models and its potential as a COVID-19 therapeutic candidate.

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