scholarly journals Development and Characterization of a Sin Nombre Virus Transmission Model in Peromyscus maniculatus

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 183 ◽  
Author(s):  
Bryce Warner ◽  
Derek Stein ◽  
Bryan Griffin ◽  
Kevin Tierney ◽  
Anders Leung ◽  
...  
Keyword(s):  
Peromyscus Maniculatus ◽  
Deer Mouse ◽  
Virus Transmission ◽  
Transmission Model ◽  
Deer Mice ◽  
Sin Nombre Virus ◽  
Infection Model ◽  
Main Driver ◽  
Heat Shock Responses

In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35–40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have been performed examining its transmission in deer mouse populations. Studying SNV and other hantaviruses can be difficult due to the need to propagate the virus in vivo for subsequent experiments. We show that when compared with standard intramuscular infection, the intraperitoneal infection of deer mice can be as effective in producing SNV stocks with a high viral RNA copy number, and this method of infection provides a more reproducible infection model. Furthermore, the age and sex of the infected deer mice have little effect on viral replication and shedding. We also describe a reliable model of direct experimental SNV transmission. We examined the transmission of SNV between deer mice and found that direct contact between deer mice is the main driver of SNV transmission rather than exposure to contaminated excreta/secreta, which is thought to be the main driver of transmission of the virus to humans. Furthermore, increases in heat shock responses or testosterone levels in SNV-infected deer mice do not increase the replication, shedding, or rate of transmission. Here, we have demonstrated a model for the transmission of SNV between deer mice, the natural rodent reservoir for the virus. The use of this model will have important implications for further examining SNV transmission and in developing strategies for the prevention of SNV infection in deer mouse populations.

scholarly journals Temporal and Spatial Analysis of Sin Nombre Virus Quasispecies in Naturally Infected Rodents

1999 ◽  
Vol 73 (11) ◽  
pp. 9544-9554 ◽  
Author(s):  
Ralph Feuer ◽  
John D. Boone ◽  
Dale Netski ◽  
Sergey P. Morzunov ◽  
Stephen C. St. Jeor
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Deer Mouse ◽  
Viral Rna ◽  
Deer Mice ◽  
Sin Nombre Virus ◽  
Viral Diversity ◽  
Host Immune System ◽  
Natural Setting

ABSTRACT Sin Nombre virus (SNV) is thought to establish a persistent infection in its natural reservoir, the deer mouse (Peromyscus maniculatus), despite a strong host immune response. SNV-specific neutralizing antibodies were routinely detected in deer mice which maintained virus RNA in the blood and lungs. To determine whether viral diversity played a role in SNV persistence and immune escape in deer mice, we measured the prevalence of virus quasispecies in infected rodents over time in a natural setting. Mark-recapture studies provided serial blood samples from naturally infected deer mice, which were sequentially analyzed for SNV diversity. Viral RNA was detected over a period of months in these rodents in the presence of circulating antibodies specific for SNV. Nucleotide and amino acid substitutions were observed in viral clones from all time points analyzed, including changes in the immunodominant domain of glycoprotein 1 and the 3′ small segment noncoding region of the genome. Viral RNA was also detected in seven different organs of sacrificed deer mice. Analysis of organ-specific viral clones revealed major disparities in the level of viral diversity between organs, specifically between the spleen (high diversity) and the lung and liver (low diversity). These results demonstrate the ability of SNV to mutate and generate quasispecies in vivo, which may have implications for viral persistence and possible escape from the host immune system.

scholarly journals Phylogeography of the deer mouse (Peromyscus maniculatus) provides a predictive framework for research on hantaviruses

2006 ◽  
Vol 87 (7) ◽  
pp. 1997-2003 ◽  
Author(s):  
Jerry W. Dragoo ◽  
J. Alden Lackey ◽  
Kathryn E. Moore ◽  
Enrique P. Lessa ◽  
Joseph A. Cook ◽  
...  
Keyword(s):  
Disease Transmission ◽  
Peromyscus Maniculatus ◽  
Deer Mouse ◽  
Deer Mice ◽  
Sin Nombre Virus ◽  
Rodent Host ◽  
Bayesian Analyses ◽  
Future Studies ◽  
Geographical Regions ◽  
Virus Strains

Phylogeographical partitioning of Sin Nombre and Monongahela viruses (hantaviruses) may reflect that of their primary rodent host, the deer mouse (Peromyscus maniculatus). Lack of a comprehensive assessment of phylogeographical variation of the host has precluded the possibility of predicting spatial limits of existing strains of these viruses or geographical regions where novel viral strains might emerge. The complete cytochrome b gene was sequenced for 206 deer mice collected from sites throughout North America to provide a foundation for future studies of spatial structure and evolution of this ubiquitous host. Bayesian analyses of these sequences partitioned deer mice into six largely allopatric lineages, some of which may represent unrecognized species. The geographical distributions of these lineages were probably shaped by Quaternary climatic events. Populations of mice were apparently restricted to refugia during glacial advances, where they experienced genetic divergence. Expansion of these populations, following climatic amelioration, brought genetically distinctive forms into contact. Occurrence of parallel changes in virus strains can now be explored in appropriate regions. In New Mexico, for example, near the location where Sin Nombre virus was first discovered, there are three genetically distinctive lineages of deer mice whose geographical ranges need to be delineated precisely. The phylogeography of P. maniculatus provides a framework for interpreting geographical variability, not only in hosts, but also in associated viral variants and disease transmission, and an opportunity to predict the potential geographical distribution of newly emerging viral strains.

scholarly journals Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity

2020 ◽  
Vol 117 (43) ◽  
pp. 26955-26965 ◽  
Author(s):  
Suzanne J. F. Kaptein ◽  
Sofie Jacobs ◽  
Lana Langendries ◽  
Laura Seldeslachts ◽  
Sebastiaan ter Horst ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Virus Transmission ◽  
Small Animal ◽  
Antiviral Effect ◽  
Viral Disease ◽  
Scientific Basis ◽  
Infection Model ◽  
High Dose ◽  
High Doses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2−infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.

scholarly journals Contact heterogeneity in deer mice: implications for Sin Nombre virus transmission

2009 ◽  
Vol 276 (1660) ◽  
pp. 1305-1312 ◽  
Author(s):  
Christine A Clay ◽  
Erin M Lehmer ◽  
Andrea Previtali ◽  
Stephen St. Jeor ◽  
M. Denise Dearing
Keyword(s):  
Great Basin ◽  
Large Fraction ◽  
General Pattern ◽  
Virus Transmission ◽  
Pathogen Transmission ◽  
Contact Dynamics ◽  
Deer Mice ◽  
Sin Nombre Virus ◽  
Transmission Potential ◽  
Contact Rates

Heterogeneities within disease hosts suggest that not all individuals have the same probability of transmitting disease or becoming infected. This heterogeneity is thought to be due to dissimilarity in susceptibility and exposure among hosts. As such, it has been proposed that many host–pathogen systems follow the general pattern whereby a small fraction of the population accounts for a large fraction of the pathogen transmission. This disparity in transmission dynamics is often referred to as ‘20/80 Rule’, i.e. approximately 20 per cent of the hosts are responsible for 80 per cent of pathogen transmission. We investigated the role of heterogeneity in contact rates among potential hosts of a directly transmitted pathogen by examining Sin Nombre virus (SNV) in deer mice ( Peromyscus maniculatus ). Using foraging arenas and powder marking, we documented contacts between wild deer mice in Great Basin Desert, central Utah. Our findings demonstrated heterogeneity among deer mice, both in frequency and in duration of contacts with other deer mice. Contact dynamics appear to follow the general pattern that a minority of the population accounts for a majority of the contacts. We found that 20 per cent of individuals in the population were responsible for roughly 80 per cent of the contacts observed. Larger-bodied individuals appear to be the functional group with the greatest SNV transmission potential. Contrary to our predictions, transmission potential was not influenced by breeding condition or sex.

The ecology of the deer mouse, Peromyscus maniculatus, in a coastal coniferous forest. III. Stomach-weight variation

1974 ◽  
Vol 52 (11) ◽  
pp. 1311-1315 ◽  
Author(s):  
J. Harling ◽  
R. M. F. S. Sadleir
Keyword(s):  
Frequency Distribution ◽  
Seasonal Changes ◽  
Peromyscus Maniculatus ◽  
Deer Mouse ◽  
Coniferous Forest ◽  
Deer Mice ◽  
Full Stomach ◽  
Weight Variation ◽  
Consumption Rates ◽  
Stomach Weight

The frequency distribution of over 600 stomach weights of deer mice showed considerable variation and was highly skewed. Because of the difficulty of defining a "full" stomach, it was not possible to use the weights of stomachs sampled to estimate consumption rates. There were no significant seasonal changes in mean stomach weights over a 3-year study and no relationship between stomach weights and sexual condition was found.

scholarly journals Experimental infection model for Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus)

2000 ◽  
Vol 97 (19) ◽  
pp. 10578-10583 ◽  
Author(s):  
J. Botten ◽  
K. Mirowsky ◽  
D. Kusewitt ◽  
M. Bharadwaj ◽  
J. Yee ◽  
...  
Keyword(s):  
Experimental Infection ◽  
Peromyscus Maniculatus ◽  
Deer Mouse ◽  
Infection Model ◽  
Experimental Infection Model

Sodium pentobarbital induced alterations in regional distribution of blood in Peromyscus maniculatus (deer mouse) and Eptesicus fuscus (big brown bat)

1977 ◽  
Vol 55 (12) ◽  
pp. 1931-1935 ◽  
Author(s):  
Josefine C. Rauch ◽  
David D. Beatty
Keyword(s):  
Skeletal Muscle ◽  
Peromyscus Maniculatus ◽  
Deer Mouse ◽  
General Pattern ◽  
Regional Distribution ◽  
Deer Mice ◽  
Sodium Pentobarbital ◽  
Blood Distribution ◽  
Big Brown Bat ◽  
Pentobarbital Anaesthesia

This study demonstrates the effect of sodium pentobarbital anaesthesia on heart rate (HR) and blood distribution (Sapirstein method) in the deer mouse, Peromyscus maniculatus, and in the big brown bat, Eptesicus fuscus.Resting HR's average 400 beats/min and 334 beats/min in deer mice and bats, respectively. Administration of 40 mg/kg sodium pentobarbital results in marked tachycardia in deer mice but not in bats. A dose of 60 mg/kg causes a slight increase of HR above resting values in the mice and a significant decrease in the bats. The comparatively low HR's in bats are considered to be due to their lowering of body temperature to near environmental levels.The general pattern of blood distribution is comparable between the two species investigated. Sodium pentobarbital administration results in a pronounced redistribution of blood which includes an increase in the fractional delivery of cardiac output to viscera of the abdomen primarily at the expense of skeletal muscle.

Population Dynamics of Deer Mice, Peromyscus maniculatus, and Yellow-pine Chipmunks, Tamias amoenus, in Old Field and Orchard Habitats

2004 ◽  
Vol 118 (3) ◽  
pp. 299 ◽  
Author(s):  
Thomas P. Sullivan ◽  
Druscilla S. Sullivan ◽  
Eugene J. Hogue
Keyword(s):  
Population Dynamics ◽  
Peromyscus Maniculatus ◽  
Deer Mouse ◽  
Detailed Comparison ◽  
Rodent Species ◽  
Deer Mice ◽  
Old Field ◽  
Tamias Amoenus ◽  
Yellow Pine ◽  
Mammal Communities

There are often several rodent species included in the small mammal communities in orchard agro-ecosystems. This study was designed to test the hypothesis that the population levels of Deer Mice (Peromyscus maniculatus) and Yellow-pine Chipmunks (Tamias amoenus) would be enhanced in old field compared with orchard habitats. Rodent populations were intensively livetrapped in replicate old field and orchard sites over a four-year period at Summerland, British Columbia, Canada. Deer Mouse populations were, on average, significantly higher (2.5 – 3.4 times) in the old field than orchard sites in summer and winter periods. Mean numbers/ha of Deer Mice ranged from 12.1 to 60.4 in old field sites and from 3.3 to 19.9 in orchard sites. Breeding seasons in orchards were significantly longer than those in old field sites, in terms of proportion of reproductive male Deer Mice. Recruitment of new animals and early juvenile survival of Deer Mice were similar in orchard and old field sites. Populations of Yellow-pine Chipmunks ranged in mean abundance/ha from 5.6 – 19.0 in old field sites and from 1.9 – 17.5 on one orchard site, with no difference in mean abundance in 2 of 4 years of the study. Recruitment and mean survival of Yellow-pine Chipmunks also followed this pattern. This study is the first detailed comparison of the population dynamics of these rodent species in old field and orchard habitats. These species should be able to maintain their population levels and help contribute to a diversity of small mammals in this agrarian landscape.

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