The transmission rate of MCMV in house mice in pens: implications for virally vectored immunocontraception

2009 ◽  
Vol 36 (5) ◽  
pp. 386 ◽  
Author(s):  
A. D. Arthur ◽  
C. J. Krebs ◽  
R. P. Pech ◽  
L. N. Farroway ◽  
G. R. Singleton

Pest mammals have severe economic, environmental and social impacts throughout the world. Fertility control could reduce these impacts. Murine cytomegalovirus (MCMV) is being considered as an immunocontraceptive vector to control outbreaks of house mice (Mus domesticus) in Australian grain-growing regions. For successful control, a modified MCMV must transmit at a sufficient rate to keep populations of house mice below acceptable economic thresholds. We used disease models developed previously by using observations of free-ranging wild-mouse populations to assess the transmission rate of two laboratory strains of MCMV (N1 and G4) collected in a previous experiment. Mice contained in pens were deliberately infected with the N1 strain only, or with the N1 strain followed by the G4 strain. If we assume density-dependent transmission, which is the more likely mode of transmission, we found the N1 strain of MCMV transmitted at a rate ~1/300 of the rate of field strains, and hence too slowly for successful virally vectored immunocontraception (VVIC). If transmission was frequency-dependent, the rate of transmission was ~1/3 of the rate of field strains, and hence may allow successful VVIC. The G4 strain transmitted at least as slowly as the N1 strain, and possibly much more slowly; however, we could not determine whether this was an inherent property of the G4 strain or whether it was caused by competition with the N1 strain. Given the reliance of successful VVIC on rapid transmission, we recommend that future work in any VVIC system explicitly quantifies the transmission rate of recombinant viruses relative to field strains, both in the presence and absence of competing strains.

2005 ◽  
Vol 32 (7) ◽  
pp. 631 ◽  
Author(s):  
A. D. Arthur ◽  
R. P. Pech ◽  
G. R. Singleton

Virally vectored immunocontraception using a modified murine cytomegalovirus (MCMV) is being developed for the control of house mice in Australia. In this paper, we develop disease–host models using a combination of laboratory and field data. We then combine these models with a model of a previous mouse population outbreak to explore the likely effectiveness of modified MCMV for controlling mice. Models of homogeneous mixing with and without vertical/pseudovertical transmission provided reasonable fits to field serological data collected during the onset and development of a mouse population outbreak in south-eastern Australia. Both models include the high transmission rate of MCMV suggested by the data. We found no strong support for non-linear contact rates or heterogeneous mixing. When applied to a past outbreak of mice both models gave similar results and suggested that immunocontraceptive MCMV could be effective at reducing agricultural damage to acceptable levels. Successful control was still possible when lags in the development of infertility of up to 10 weeks were added to the model, provided high levels of infertility were achieved. These lags were added because mice can become pregnant just before becoming infertile – the resultant litter would not emerge for 6–7 weeks. Trade-offs between two parameters that could be altered by engineering strains of MCMV – the level of infertility in infected mice and the virus transmission rate – were explored and suggest that a variety of parameter combinations could produce successful control. Our results are encouraging for the future development of virally vectored immunocontraception control of house mice, but future work will need to consider some of the assumptions of these single-strain models.


2004 ◽  
Vol 31 (4) ◽  
pp. 369 ◽  
Author(s):  
Jens Jacob ◽  
Duncan R. Sutherland

The murine cytomegalovirus (MCMV) may be used as a vector for fertility control in house mice, which are a significant agricultural pest in south-eastern Australia. The transmission of MCMV can be density dependent and is mostly subclinical in its effect on mice; however, little is known about which individual parameters influence whether an animal is likely to be infected or not.We examined the impact of age and reproductive history on seroprevalence of MCMV in house mice during the breeding season. MCMV seroprevalence was density dependent and there was a linear increase in seroprevalence with increasing age, starting at 25% for 1-month-old mice and 100% for all individuals older than five months. There was no clear indication that the number of previous pregnancies was related to MCMV seroprevalence.The high prevalence of MCMV among adult female house mice (84%) implies that an Australian field strain of MCMV could be a promising vector for an immunocontraceptive for house mice.


2002 ◽  
Vol 29 (1) ◽  
pp. 11 ◽  
Author(s):  
L. N. Farroway ◽  
G. R. Singleton ◽  
M. A. Lawson ◽  
D. A. Jones

Feral house mice are a significant agricultural pest in south-eastern Australia. Fertility control is favoured as a long-term control strategy, using murine cytomegalovirus (MCMV) as a viral delivery system for an immunocontraceptive. We examined the impact of one and two non-sterilising field strains of MCMV on populations of house mice housed under semi-natural conditions. MCMV had no effect on the proportion of females pregnant or lactating or on the number of placental scars per female. However, females in enclosures with two strains of MCMV produced fewer litters. No impact of MCMV was detected on adult survival, with high survival (>95%) detected in all enclosures. Similar numbers of the first cohort of young entered the trappable population of all enclosures. There was no significant impact of MCMV on survival of young mice, although there was a trend for reduced numbers of the second cohort of young and less successful recruitment in enclosures with two strains of MCMV. The two cohorts of young mice in enclosures with MCMV had poorer body condition. These impacts of infection on young mice imply that MCMV may have negative effects on survival only when the host immune system is not fully developed or the host is immunocompromised. Overall, there was no effect of MCMV on the rate of increase of the mouse populations. Therefore, the effects of MCMV were minor at a demographic level, confirming the suitability of an Australian field strain of MCMV as a vector for an immunocontraceptive of mice.


BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Raman Akinyanju Lawal ◽  
Uma P. Arora ◽  
Beth L. Dumont

Abstract Background Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Results Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Conclusions Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.


Virology ◽  
2018 ◽  
Vol 521 ◽  
pp. 92-98 ◽  
Author(s):  
Dagmar Čížková ◽  
Stuart J.E. Baird ◽  
Jana Těšíková ◽  
Sebastian Voigt ◽  
Ďureje Ľudovít ◽  
...  

2020 ◽  
Vol 1 (1) ◽  
pp. 61-75 ◽  
Author(s):  
Abby M. McClain ◽  
Risa Daniels ◽  
Forrest M. Gomez ◽  
Sam H. Ridgway ◽  
Ryan Takeshita ◽  
...  

Bottlenose dolphins (Tursiops truncatus) have a worldwide distribution in temperate and tropical waters and often inhabit estuarine environments, indicating their ability to maintain homeostasis in low salinity for limited periods of time. Epidermal and biochemical changes associated with low salinity exposure have been documented in stranded bottlenose dolphins; however, these animals are often found severely debilitated or deceased and in poor condition. Dolphins in the U.S. Navy Marine Mammal Program travel globally, navigating varied environments comparable to those in which free-ranging dolphins are observed. A retrospective analysis was performed of medical records from 46 Navy dolphins and blood samples from 43 Navy dolphins exposed to a variety of salinity levels for different durations over 43 years (from 1967–2010). Blood values from samples collected during low salinity environmental exposure (salinity ranging from 0–30 parts per thousand (ppt) were compared to samples collected while those same animals were in a seawater environment (31–35 ppt). Epidermal changes associated with low salinity exposure were also assessed. Significant decreases in serum sodium, chloride, and calculated serum osmolality and significant increases in blood urea nitrogen and aldosterone were observed in blood samples collected during low salinity exposure. Epidermal changes were observed in 35% of the animals that spent time in low salinity waters. The prevalence of epidermal changes was inversely proportional to the level of salinity to which the animals were exposed. Future work is necessary to fully comprehend the impacts of low salinity exposure in bottlenose dolphins, but the physiological changes observed in this study will help improve our understanding of the upper limit of duration and the lower limit of salinity in which a bottlenose dolphin can maintain homeostasis.


1997 ◽  
Vol 9 (1) ◽  
pp. 77 ◽  
Author(s):  
A. J. Robinson ◽  
R. Jackson ◽  
P. Kerr ◽  
J. Merchant ◽  
I. Parer ◽  
...  

The history of myxoma virus, its use in Australia as a mortality agent and the development of the virus as a vector for controlling fertility in wild rabbit populations in Australia is reviewed. Myxoma virus recombinants have been constructed to express model antigens. Four potential insertion sites in the genome have been identified and two have been used to construct single and double recombinant viruses expressing Escherichia colienzymes β-galactosidase and β-glucuronidase. Another recombinant expressing an influenza virus haemagglutinin gene (A/PR8/34) induced high and sustained antibody responses following intradermal inoculation in rabbits. To demonstrate the potential of introducing a recombinant virus into wild rabbit populations, a virus containing a natural deletion was released at four field locations. Preliminary analysis of the data has shown that the introduced virus spread well on 3 of the 4 locations. The steps being taken to address the ethical and safety implications of the introduction of a recombinant virus into the field are discussed.


2008 ◽  
Vol 35 (6) ◽  
pp. 487 ◽  
Author(s):  
Jens Jacob ◽  
Grant R. Singleton ◽  
Lyn A. Hinds

Ricefield rats (Rattus argentiventer) in south-east Asian rice fields and house mice (Mus domesticus) in Australian grain fields are major pest species. They cause damage before and after harvest and carry zoonotic diseases. For both species, management techniques have been pursued using the approach of immunocontraceptive vaccination. We review results from a series of enclosure and field studies conducted with these species to assess the effects of fertility control in small rodents. In the experiments, fertility control was simulated by tubal ligation, ovariectomy or progesterone treatment. A once-off sterilisation of 50–75% of enclosed founder females considerably reduced reproductive output of ricefield rat populations until the end of the reproductive period. In house mice, similar success was achieved when a sterility level of 67% of female founders and offspring was maintained. Repeated antifertility treatments are required because of the much longer breeding period of house mice versus ricefield rats. Comparing the results of enclosure trials with the outcome of simulation models suggests that partial compensation of treatment effects can occur through enhanced reproduction of the remaining fertile females and improved survival of juveniles. However, such compensatory effects as well as behavioural consequences of sterility in field populations are not likely to prevent the management effect at the population level. The challenge for effective fertility control of small rodents in the field is the wide-scale delivery of an antifertility treatment to founders at the beginning of the breeding season and to fertile immigrants that are recruited into the population, which otherwise contribute to the reproductive output at the population level. Future research efforts should focus on species-specific techniques and on agents that can be effectively delivered via bait.


Author(s):  
Nicole L. Washington ◽  
Karthik Gangavarapu ◽  
Mark Zeller ◽  
Alexandre Bolze ◽  
Elizabeth T. Cirulli ◽  
...  

SummaryAs of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.


2020 ◽  
Vol 42 (1) ◽  
pp. 27
Author(s):  
J. D. Scasta ◽  
M. Adams ◽  
R. Gibbs ◽  
B. Fleury

Management of free-ranging horses (Equus ferus caballus) is a complex socio-ecological issue in Australia (AU), New Zealand (NZ), and the United States (US). In these countries, horses are the results of colonial introductions and occupy very harsh rangeland environments exerting a grazing disturbance that has generated ecological concerns. Although many social and ecological concerns are similar, each country also has nuances. In 2018, we conducted a field-based comparison of AU, NZ, and US using an inductive approach to identify similarities, differences, and emerging themes through conversations with >100 individuals from New South Wales Australia, the North Island of New Zealand, and the western US. Additional data sources included field observations and archival documents. Consistent emergent themes identified included: strong public emotion, politicization of management, population growth concerns, negative ecological impact concerns, agreement that horses should be treated humanely, disagreement as to what practices were the most humane, interest and scepticism about fertility control, the need for transparency, compromise to accommodating horses and acknowledgement of social values, and recognition that collaboration is the only means to achieve both healthy rangelands and healthy horses. Unique themes identified included: NZ empowering advocate groups to become part of the solution, conflict between horses and livestock is a mostly US conflict, equids originated in the US, concern about the sustainability of adoption programs, different expectations/options for management on private lands, cultural history such as brumby running in AU, permanent branding of horses in the US, litigation as a uniquely US strategy (although a judgement on recent AU litigation is pending), government data accepted to guide removals in NZ but not always in AU or US, and complex heterogeneous land surface ownership patterns makes management difficult in the US. The difficulty of horse management in these countries is attributed to social intricacies rather than biological/ecological gaps of knowledge.


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