Natural rodent model of viral transmission reveals biological features of virus population dynamics

2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Elizabeth J. Fay ◽  
Keir M. Balla ◽  
Shanley N. Roach ◽  
Frances K. Shepherd ◽  
Dira S. Putri ◽  
...  
Keyword(s):  
Virus Transmission ◽  
Experimental Models ◽  
Model System ◽  
Host Factors ◽  
Virus Population ◽  
Laboratory Mice ◽  
Emerging Viruses ◽  
New Host ◽  
New Members ◽  
Biological Features

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats—which harbor natural rodent pathogens—are cohoused with laboratory mice. This “dirty” mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.

scholarly journals 491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S312-S312
Author(s):  
Seth D Judson ◽  
Vincent J Munster
Keyword(s):  
High Risk ◽  
Severe Disease ◽  
Experimental Studies ◽  
Virus Transmission ◽  
Nosocomial Transmission ◽  
Medical Procedures ◽  
Emerging Viruses ◽  
Zoonotic Viruses ◽  
Increased Risk ◽  
Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

scholarly journals Decreased Virus Population Diversity in p53-Null Mice Infected with Weakly Oncogenic Abelson Virus

2005 ◽  
Vol 79 (18) ◽  
pp. 11618-11626 ◽  
Author(s):  
Erica Marchlik ◽  
Richard Kalman ◽  
Naomi Rosenberg
Keyword(s):  
Tumor Suppressor ◽  
Recombination Event ◽  
Leukemia Virus ◽  
Population Diversity ◽  
Virus Population ◽  
Wild Type ◽  
Emerging Viruses ◽  
Host Genes ◽  
Murine Leukemia

ABSTRACT The Abelson murine leukemia virus (Ab-MLV), like other retroviruses that contain v-onc genes, arose following a recombination event between a replicating retrovirus and a cellular oncogene. Although experimentally validated models have been presented to address the mechanism by which oncogene capture occurs, very little is known about the events that influence emerging viruses following the recombination event that incorporates the cellular sequences. One feature that may play a role is the genetic makeup of the host in which the virus arises; a number of host genes, including oncogenes and tumor suppressor genes, have been shown to affect the pathogenesis of many murine leukemia viruses. To examine how a host gene might affect an emerging v-onc gene-containing retrovirus, we studied the weakly oncogenic Ab-MLV-P90A strain, a mutant that generates highly oncogenic variants in vivo, and compared the viral populations in normal mice and mice lacking the p53 tumor suppressor gene. While variants arose in both p53 +/+ and p53 − / − tumors, the samples from the wild-type animals contained a more diverse virus population. Differences in virus population diversity were not observed when wild-type and null animals were infected with a highly oncogenic wild-type strain of Ab-MLV. These results indicate that p53, and presumably other host genes, affects the selective forces that operate on virus populations in vivo and likely influences the evolution of oncogenic retroviruses such as Ab-MLV.

scholarly journals Identification of unrecognized host factors promoting HIV-1 latency

2020 ◽  
Vol 16 (12) ◽  
pp. e1009055
Author(s):  
Zichong Li ◽  
Cyrus Hajian ◽  
Warner C. Greene
Keyword(s):  
Rna Polymerase Ii ◽  
Full Range ◽  
Screening Strategy ◽  
Host Factors ◽  
Host Cells ◽  
Hiv Latency ◽  
New Host ◽  
High Background ◽  
Hiv 1 ◽  
Host Genes

To counter HIV latency, it is important to develop a better understanding of the full range of host factors promoting latency. Their identification could suggest new strategies to reactivate latent proviruses and subsequently kill the host cells (“shock and kill”), or to permanently silence these latent proviruses (“block and lock”). We recently developed a screening strategy termed “Reiterative Enrichment and Authentication of CRISPRi Targets” (REACT) that can unambiguously identify host genes promoting HIV latency, even in the presence of high background “noise” produced by the stochastic nature of HIV reactivation. After applying this strategy in four cell lines displaying different levels of HIV inducibility, we identified FTSJ3, TMEM178A, NICN1 and the Integrator Complex as host genes promoting HIV latency. shRNA knockdown of these four repressive factors significantly enhances HIV expression in primary CD4 T cells, and active HIV infection is preferentially found in cells expressing lower levels of these four factors. Mechanistically, we found that downregulation of these newly identified host inhibitors stimulates different stages of RNA Polymerase II-mediated transcription of HIV-1. The identification and validation of these new host inhibitors provide insight into the novel mechanisms that maintain HIV latency even when cells are activated and undergo cell division.

scholarly journals Hepatitis C Virus Envelope Glycoprotein Fitness Defines Virus Population Composition following Transmission to a New Host

2012 ◽  
Vol 86 (22) ◽  
pp. 11956-11966 ◽  
Author(s):  
R. J. P. Brown ◽  
N. Hudson ◽  
G. Wilson ◽  
S. U. Rehman ◽  
S. Jabbari ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Envelope Glycoprotein ◽  
Virus Population ◽  
Population Composition ◽  
Virus Envelope ◽  
New Host

scholarly journals Unstressing intemperate models: how cold stress undermines mouse modeling

2012 ◽  
Vol 209 (6) ◽  
pp. 1069-1074 ◽  
Author(s):  
Christopher L. Karp
Keyword(s):  
Cold Stress ◽  
Biomedical Research ◽  
Current Model ◽  
Environmental Variable ◽  
Model System ◽  
Laboratory Mice ◽  
Therapeutic Approaches ◽  
Mechanistic Analysis ◽  
Mouse Modeling

Mus musculus enjoys pride of place at the center of contemporary biomedical research. Despite being the current model system of choice for in vivo mechanistic analysis, mice have clear limitations. The literature is littered with examples of therapeutic approaches that showed promise in mouse models but failed in clinical trials. More generally, mice often provide poor mimics of the human diseases being modeled. Available data suggest that the cold stress to which laboratory mice are ubiquitously subjected profoundly affects mouse physiology in ways that impair the modeling of human homeostasis and disease. Experimental attention to this key, albeit largely ignored, environmental variable is likely to have a broad transformative effect on biomedical research.

scholarly journals Animal Virus Ecology and Evolution Are Shaped by the Virus Host-Body Infiltration and Colonization Pattern

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 72
Author(s):  
Jan Slingenbergh
Keyword(s):  
Virus Transmission ◽  
Mass Rearing ◽  
Virus Genome ◽  
Organ System ◽  
Emerging Viruses ◽  
Cell Infection ◽  
Host Environment ◽  
Animal Virus ◽  
Host Tropism ◽  
System Involvement

The current classification of animal viruses is largely based on the virus molecular world. Less attention is given to why and how virus fitness results from the success of virus transmission. Virus transmission reflects the infection-shedding-transmission dynamics, and with it, the organ system involvement and other, macroscopic dimensions of the host environment. This study describes the transmission ecology of the world main livestock viruses, 36 in total, a mix of RNA, DNA and retroviruses. Following an iterative process, the viruses are virtually ranked in an outer- to inner-body fashion, by organ system, on ecological grounds. Also portrayed are the shifts in virus host tropism and virus genome. The synthesis of the findings reveals a predictive virus evolution framework, based on the outer- to inner-body changes in the interplay of host environment-transmission modes-organ system involvement-host cell infection cycle-virus genome. Outer-body viruses opportunistically respond to the variation in the external environment. For example, respiratory and enteric viruses tend to be associated with poultry and pig mass rearing. Ruminant and equine viruses tend to be more deep-rooted and host-specific, and also establish themselves in the vital inner-body systems. It is concluded that the framework may assist the study of new emerging viruses and pandemic risks.

scholarly journals The Interactomes of Influenza Virus NS1 and NS2 Proteins Identify New Host Factors and Provide Insights for ADAR1 Playing a Supportive Role in Virus Replication

2013 ◽  
Vol 9 (7) ◽  
pp. e1003440 ◽  
Author(s):  
Benoît de Chassey ◽  
Anne Aublin-Gex ◽  
Alessia Ruggieri ◽  
Laurène Meyniel-Schicklin ◽  
Fabrine Pradezynski ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Host Factors ◽  
New Host ◽  
Supportive Role

scholarly journals Bacteriophage Migration via Nematode Vectors: Host-Parasite-Consumer Interactions in Laboratory Microcosms

2006 ◽  
Vol 72 (3) ◽  
pp. 1974-1979 ◽  
Author(s):  
John J. Dennehy ◽  
Nicholas A. Friedenberg ◽  
Yul W. Yang ◽  
Paul E. Turner
Keyword(s):  
Experimental Studies ◽  
Virus Transmission ◽  
Growth Dynamics ◽  
Model System ◽  
Pathogen Transmission ◽  
Trophic Levels ◽  
Future Research ◽  
Evolution Of Virulence ◽  
Consumer Interactions ◽  
Host Parasite

ABSTRACT Pathogens vectored by nematodes pose serious agricultural, economic, and health threats; however, little is known of the ecological and evolutionary aspects of pathogen transmission by nematodes. Here we describe a novel model system with two trophic levels, bacteriophages and nematodes, each of which competes for bacteria. We demonstrate for the first time that nematodes are capable of transmitting phages between spatially distinct patches of bacteria. This model system has considerable advantages, including the ease of maintenance and manipulation at the laboratory bench, the ability to observe many generations in short periods, and the capacity to freeze evolved strains for later comparison to their ancestors. More generally, experimental studies of complex multispecies interactions, host-pathogen coevolution, disease dynamics, and the evolution of virulence may benefit from this model system because current models (e.g., chickens, mosquitoes, and malaria parasites) are costly to maintain, are difficult to manipulate, and require considerable space. Our initial explorations centered on independently assessing the impacts of nematode, bacterium, and phage population densities on virus migration between host patches. Our results indicated that virus transmission increases with worm density and host bacterial abundance; however, transmission decreases with initial phage abundance, perhaps because viruses eliminate available hosts before migration can occur. We discuss the microbial growth dynamics that underlie these results, suggest mechanistic explanations for nematode transmission of phages, and propose intriguing possibilities for future research.

scholarly journals A tractable Drosophila cell system enables rapid identification of Acinetobacter baumannii host factors

2020 ◽  
Author(s):  
Qing-Ming Qin ◽  
Jianwu Pei ◽  
Gabriel Gomez ◽  
Allison Rice-Ficht ◽  
Thomas A. Ficht ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Model System ◽  
Host Factors ◽  
Host Cells ◽  
Bacterial Invasion ◽  
Organelle Biogenesis ◽  
Drosophila Cell

AbstractAcinetobacter baumannii is an important causative agent of nosocomial infections worldwide. The pathogen also readily acquires resistance to antibiotics, and pan-resistant strains have been reported. A. baumannii is widely regarded as an extracellular bacterial pathogen. However, accumulating evidence demonstrates that the pathogen can invade, survive or persist in infected mammalian cells. Unfortunately, the molecular mechanisms controlling these processes remain poorly understood. Here, we show that Drosophila S2 cells provide several attractive advantages as a model system for investigating the intracellular lifestyle of the pathogen, including susceptibility to bacterial intracellular replication and limited infection-induced host cell death. We also show that the Drosophila system can be used to rapidly identify host factors, including MAP kinase proteins, which confer susceptibility to intracellular parasitism. Finally, analysis of the Drosophila system suggested that host proteins that regulate organelle biogenesis and membrane trafficking contribute to regulating the intracellular lifestyle of the pathogen. Taken together, these findings establish a novel model system for elucidating interactions between A. baumannii and host cells, define new factors that regulate bacterial invasion or intracellular persistence, and identify subcellular compartments in host cells that interact with the pathogen.

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