Emerging and Miscellaneous Viral Infections

• The infectious diseases described in this chapter are either: (1) diseases of humans or other animals generally transmitted through contact with the secretions or excretions of rodents (hantaviruses, arenaviruses, and encephalomyocarditis virus), swine (hepatitis E virus), monkeys (Ebola virus), or bats (systemic coronaviruses);(2) common diseases of humans where the role of companion animals in transmission has been investigated (enteroviruses, SARS-CoV-2);(3) diseases of significant importance to the agricultural industry (foot-and-mouth disease virus, vesicular exanthema, encephalomyocarditis virus);or (4) significant diseases of potential prey of dogs and cats (rabbit hemorrhagic disease virus). • Clinical illness has not always been confirmed in dogs and cats with these infections, but evidence of seroconversion to these viruses exists. • In some cases, concern has been raised in the possible role of dogs and cats in zoonotic transmission;this has been heightened by the COVID-19 pandemic. • In general, research suggests that dogs and cats do not play a major role in transmission of these viruses, but the potential exists should new viral variants emerge. © 2021 Elsevier Inc. All rights reserved.

Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research. (Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research.)

This special issue contains 23 articles that discuss various aspects of antiviral research, focusing on the contributions and legacy of Dr. Mike Bray, the retiring Editor-in-Chief of Antiviral Research. The articles cover a range of topics, including the underappreciated mouse model for Ebola virus disease, the history and impact of the mouse-adapted Ebola virus model, and the characterisation of CD-1 mice infected with different strains of Ebola virus. Other articles delve into transplacental vertical transmission of flaviviruses, the development of reverse genetic systems for SARS-CoV-2, and the mechanisms of action and drug resistance of nucleotide analogues against the virus. The special issue also explores therapeutics for flaviviral infections, alternative splicing in RNA virus infections, and targeted protein degradation as an antiviral approach.

The ecology of viruses in urban rodents with a focus on SARS-CoV-2.

Wild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (Rattus norvegicus) and mice (Apodemus sylvaticus) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.

Preparation and identification of broad-spectrum monoclonal antibodies against N protein of avian infectious bronchitis virus

[Objective] To prepare broad-spectrum monoclonal antibody against N protein of avian infectious bronchitis virus (IBV), so as to lay a foundation for identifying conservative domain epitope of N protein and establish a universal IBV detection method. [Method] N protein of GX-YL5, a representative strain of IBV dominant serotype in Guangxi, was expressed in prokaryote. BALB/c mice were immunized with the purified protein. After the serum titer of the immunized mice reached 104 or more, the splenocytes were fused with SP2/0 myeloma cells. After screening by indirect ELISA, monoclonal antibody was prepared by ascites-induced method. Western blotting, IFA and indirect ELISA were used to identify the titer, subtype, reaction specificity and cross-reaction spectrum. And the prepared monoclonal antibody was used for immunohistochemical detection. And the prepared monoclonal antibody was used to detect the IBV in the trachea and kidney tissues of SPF chickens artificially infected with 4 representative IBV variants (GX-N130048, GX-N160421, GX-QZ171023 and GX-QZ170728). [Result] The prepared monoclonal antibody N2D5 had a titer greater than 217 and its subtype was IgG2b. The Western blotting and IFA results showed that the monoclonal antibody N2D5 only reacted with IBV, and were negative with Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), avian leukosis virus (ALV) and Marek's disease virus (MDV). Monoclonal antibody N2D5 reacted with many genotypes in China and all 7 serotypes of IBV currently prevalent in Guangxi, including commonly used standard strains, vaccine strains and field strains. Immunohistochemistry showed that the virus signals could be detected in the trachea and kidney tissues of SPF chickens at different time after artificial infection of 3 representative IBV strains from chicken and 1 isolated strain from duck, which further proved its broad spectrum. [Conclusion] The monoclonal antibody N2D5 of IBV prepared based on hybridoma technology belongs to the IgG2b subtype. It has the characteristics of high specificity, wide response spectrum and strong binding ability with IBV. It can be used as a specific diagnostic antibody for clinical diagnosis of IBV and the study of virus distribution.

The Importance of Animal Models in Biomedical Research: Current Insights and Applications.

Animal research is considered a key element in advance of biomedical science. Although its use is controversial and raises ethical challenges, the contribution of animal models in medicine is essential for understanding the physiopathology and novel treatment alternatives for several animal and human diseases. Current pandemics' pathology, such as the 2019 Coronavirus disease, has been studied in primate, rodent, and porcine models to recognize infection routes and develop therapeutic protocols. Worldwide issues such as diabetes, obesity, neurological disorders, pain, rehabilitation medicine, and surgical techniques require studying the process in different animal species before testing them on humans. Due to their relevance, this article aims to discuss the importance of animal models in diverse lines of biomedical research by analyzing the contributions of the various species utilized in science over the past five years about key topics concerning human and animal health.

Natural killer (NK) cells: an innate defense shield against respiratory viral infections

In general, B and T lymphocytes, which are involved in adaptive immunity, are in charge of cell-mediated response and antibody-mediated immunity, respectively. Another subset of lymphocytes, known as natural killer (NK) cells, are innate effector cells. They serve as the body's initial line of defence against viral infections. They perform the task of eliminating stressed cells and are crucial for tumour immunity. These cells are capable of performing their killing function without clonal expansion and differentiation following activation. The NK cells will immediately eliminate infected host cells but other lymphocytes need lymphocyte proliferative response which takes several days and further differentiate into effector cells, so that they eliminate host cells infected by the viral pathogen. The NK cells also form a bridge between the adaptive and innate immunity and play significant roles during respiratory infection. Number and the role of NK cells correlate with the severity of severe acute respiratory syndrome (SARS);the number and the percentage of CD158b+ NK cells in severe SARS infection were significantly less in number than those with mild cases. Innate defence mechanisms, particularly NK cells, are able to control SARS infection even in the absence of T cells and antibodies, according to cellular immunological responses to SARS infection in mice. As a result, NK cells are crucial in the fight against viral infections of the respiratory system. As an innate immune system, they serve as the initial line of virus protection. It is possible to do additional research to take advantage of this NK cell trait and develop a cutting-edge therapeutic approach to fight developing respiratory viral diseases.

Truncated expression of S1 protein of Feline infectious peritonitis virus and preparation of its monoclonal antibody

In order to develop monoclonal antibody against Feline infectious peritonitis virus (FIPV) S1 protein, the truncated S1 protein (rS1) was expressed through Escherichia coli and subsequently purified. Then BALB/c mice were immunized with purified rSl. Three hybridoma cell strains, named 2D7,3D8 and 5G1, stably secreting antibodies against rSl were obtained by cell fusion and indirect ELISA screening. The identification of antibody subtype showed that antibody subtypes of 2D7,5G1 and 3d8 strains were IgG2a,IgG2a and IgGl,respectively. And the light chain of those three hybridoma cell strains was Kappa. Result of karyotype identification of hybridoma cells showed that the chromosome numbers of those three hybridoma cells were about 102,101 and 103, which was belonged to the karyotype of hybridoma. The titer of ascites antibody for indirect ELISA was 1 : 204 800, and monoclonal antibodies were purified. Moreover, all of 2D7,3D8 and 5G1 could react with rS1 by Western-blot and FIPV in cells by IFA. These data suggest that three monoclonal antibodies against rSl with good activities were ideal materials in the study of early diagnosis of FIPV and the biological function of FIPV in the future.

Evaluation of antiviral effects and toxicity of herbal medicine Vipdervir capsules

Background: Antiviral vaccine is not effective, synthetic antiviral drugs are highly toxic, leading to increased interest in herbal medicines as promising antiviral drugs. Recently, Vipdervir has been developed from medicinal herbs with the aim to support and treat diseases caused by viruses such as H5N1 and SARSCoV- 2. In the present study, we assessed Vipdervir's antiviral activity against H5N1 and SARS-CoV-2. In addition, we also evaluated the acute toxicity and repeated dose toxicity of Vipdervir in mice and rabbits, respectively. Methods: H5N1 inhibitory effect of Vipdervir was assessed using hemagglutination inhibition assay. Vipdervir's SARS-CoV-2 inhibitory effect was evaluated by Plaque Reduction Neutralization assay. Acute and repeated dose oral toxicities of Vipdervir were determined according to OECD 423 and OECD 407 guidelines, respectively. Results: Data show that Vipdervir is effective against both H5N1 and SARSCoV- 2. At concentrations of 3 mg/mL and 5 mg/mL Vipdervir completely inhibits H5N1. At a concentration of 50 g/mL Vipdervir showed an inhibitory effect on SARS-CoV-2. Acute toxicity data revealed that the LD50 of Vipdervir is greater than 35200 mg/kg, b.wt. in mice. Repeated toxicity data indicated that Vipdervir did not induce significant differences in body weight gain, hematology and clinical biochemistry in compared to the control group. The No Observed Adverse Effect Level of Vipdervir is greater than 613.8 mg/kg b.wt./day in rabbits. No delayed toxicity effects of Vipdervir were observed. Conclusion: Vipdervir capsules were found to be antiviral effective and relatively safe in the tested doses and experimental conditions.

Special Issue: Mutagenic factors in the environment impacting human and animal health. (Special Issue: Mutagenic factors in the environment impacting human and animal health.)

This special issue includes 15 articles that discuss the mutagenic effect of tobacco smoke on male fertility;environmental and occupational exposure of metals and female reproductive health;free radical biology in neurological manifestations;paternal factors in recurrent pregnancy loss;mechanical dependency of the SARS-CoV-2 virus and the renin-angiotensin-aldosterone (RAAS) axis;a perspective review on medicinal plant resources for their antimutagenic potentials;asystematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones;impact of ginseng on neurotoxicity induced by cisplatin in rats.

Living with rodent pests: Unifying stakeholder interests to prioritise pest management in rural Madagascar

Rodent pests can have major social, economic, and environmental impacts. Their management, therefore, represents a complex socio-ecological problem involving a network of stakeholders from across different sectors, with diverging and sometimes competing interests. Failure to incorporate stakeholder interests can result in ineffective or unsustainable management programmes, with unintended negative consequences for people and nature.Participatory approaches to decision-making have been proposed as suitable strategies to tackle complex problems, yet, these processes are often considered too difficult, costly, or time-consuming to implement.To facilitate a participatory approach to rodent control in Madagascar, we identified and mapped key stakeholders and developed a multisector framework for guiding rodent management programmes based on current literature and expert recommendations. We then carried out interviews and focus groups with stakeholders and end-users to validate the final framework.The final framework unifies stakeholder interests around the dimensions of People, Resources, Knowledge and Power. Combined application of the stakeholder map and framework provides decision-makers with the tools to identify stakeholder interests;to explore areas of conflict, as well as areas of agreement;and to ensure that these are addressed within the design of control programmes. As an assessment tool, the framework can also be used to evaluate the responsiveness of programmes to the needs of different stakeholders and assess whether objectives are being reached.We recommend the application of the stakeholder map and framework to encourage and strengthen participatory approaches aimed at rodent pest control. Due to the inclusive and interdisciplinary nature of the framework, it can be applied to address numerous complex social, environmental, and economic issues across scales, sectors, and systems.Read the free Plain Language Summary for this article on the Journal blog.

Pathology of animal models of COVID-19

This paper describes the pathogenesis and immunology of Macaca mulatta, Macaca fascicularis, ferrets, Syrian golden hamsters (Mesocricetus auratus), mice, cats, mink, pigs and rabbits used as models for SARS-CoV-2 infection.

The next frontier: assessing the feasibility of eradicating mammalian pests from Auckland Island. (Special Issue: Restoration of New Zealand subantarctic islands.)

Auckland Island, the fifth largest island in New Zealand, is the only island in New Zealand's subantarctic region where introduced mammalian pests remain (pigs, Sus scrofa;mice, Mus musculus;cats, Felis catus). The island has unique biodiversity and is a key site for progressing New Zealand's goal to be free of several introduced predators by 2050. Recent island eradication successes have rekindled interest in eradicating pests from Auckland Island, and for the first time considering all three pests in one project. Over a 3-year period, we tested the feasibility of eradicating pigs, mice and cats by looking at what it would take to succeed, rather than what we could practically deliver with the tools we currently have. We proposed adaptations to current methods and used an evidence-based approach by undertaking large-scale field trials to test uncertainties and emerging technologies in-situ. We gathered data and evaluated proposed methods against five established principles of eradication while considering the logistics and infrastructure requirements of the project. Eradicating pigs, mice and cats from Auckland Island is worthwhile and feasible but dependent on further development of emerging technologies and capabilities for efficient delivery with an acceptable level of risk. Three eradication operations are required with specific sequencing and timing, supported by initial establishment of infrastructure. The project needs a large investment spread over 8 to 10 years to yield permanent and internationally important benefits with low ongoing cost to sustain. The feasibility study exposed the project's scale and was used to inform decision makers, who postponed the work in 2020 in response to the economic impacts of COVID-19. The study focusses future preparations on identified planning issues and dependencies to progress project readiness in anticipation of it being launched when economic conditions allow.

Tularemia above the Treeline: Climate and Rodent Abundance Influences Exposure of a Sentinel Species, the Arctic Fox (Vulpes lagopus), to Francisella tularensis.

Tularemia is a zoonotic disease found throughout most of the northern hemisphere that may experience range expansion with warming temperatures. Rodents and lagomorphs are reservoirs for the disease, and outbreaks of tularemia often follow peaks in their abundance. As small mammals dominate the diet of arctic foxes (Vulpes lagopus), we determined whether they may serve as sentinels by identifying antibodies in live-captured and harvested foxes from northern Canada. Overall seroprevalence was 2% (CI95 1-2%) in 176 foxes harvested in 2018-2019 compared to 17% (CI95 12-22%) of 230 foxes captured live in 2011-2021. Prevalence was at an all-time high in 2018, following a peak in vole abundance in 2017. Antibodies were identified in fox pups born in 2018 and 2019, suggesting that F. tularensis was actively transmitted during the summers. High precipitation during the summer, increased snow cover and colder temperatures in May, and a higher abundance of voles were all associated with increased seroprevalence in live-captured foxes. Thus, exposure to F. tularensis is largely mediated through climate and rodent populations in the Canadian Arctic, and arctic foxes are useful sentinels for F. tularensis in northern ecosystems. Further studies should investigate whether infection impacts arctic fox survival and reproductive success in the circumpolar North.

Identification of coronaviruses in bats and rodents in northern and central Argentina.

Due to the present pandemic situation and the many animal species that are epidemiologically involved, there has been a surge of renewed interest in investigating the coronavirus (CoV) population circulating in wildlife, especially bats and rodents, which are potential reservoirs of new human pathogens. In Argentina, information about the viruses present in these mammals is very limited. To investigate the presence of coronaviruses in this country, we obtained 457 samples from hematophagous, insectivorous, and frugivorous bats and rodents from two regions of Argentina. We report here the detection of alphacoronavirus sequences in three groups of bats as well as in rodents. Phylogenetic analysis showed the closest relationships to alphacoronaviruses from Brazil.

Widespread Exposure to Mosquitoborne California Serogroup Viruses in Caribou, Arctic Fox, Red Fox, and Polar Bears, Canada.

Northern Canada is warming at 3 times the global rate. Thus, changing diversity and distribution of vectors and pathogens is an increasing health concern. California serogroup (CSG) viruses are mosquitoborne arboviruses; wildlife reservoirs in northern ecosystems have not been identified. We detected CSG virus antibodies in 63% (95% CI 58%-67%) of caribou (n = 517), 4% (95% CI 2%-7%) of Arctic foxes (n = 297), 12% (95% CI 6%-21%) of red foxes (n = 77), and 28% (95% CI 24%-33%) of polar bears (n = 377). Sex, age, and summer temperatures were positively associated with polar bear exposure; location, year, and ecotype were associated with caribou exposure. Exposure was highest in boreal caribou and increased from baseline in polar bears after warmer summers. CSG virus exposure of wildlife is linked to climate change in northern Canada and sustained surveillance could be used to measure human health risks.

Obesity and the brain. Winter Conference 2021, 7-8 December 2021

This journal issue includes 48 articles that discuss development and validation of a novel quality assessment tool to measure the quality of nutrition information online;longitudinal association between takeaway food environment and secondary school adolescents BMI and body fat percentage;dietary practices, beliefs, and behaviours among adults with inflammatory bowel disease;postpartum depression in Irish mothers and associations with infant feeding practices;the impact of dietary saturated fat replacement with unsaturated fat on the plasma lipidome and cardiometabolic disease risk;ole of brain serotonin in age-related decline in physical activity in mice;ey stakeholder perceptions of food allergies within the airline industry;sleep quality of higher education students during COVID-19 and its association with diet quality and lifestyle behaviours.

Investigation of coronavirus and hepatitis E virus in rodents in Dali City, Yunnan Province

An investigation of coronavirus (CoV) and hepatitis E virus (HEV) in rodents was performed to understand CoV and HEV infection of rodents in Dali City, Yunnan Province. Rodent samples were obtained in the four towns of Dali city through traps from August 2020 to August 2021. A total of 76 rodents belonging to six species and five genera were captured: Rattus tanezumi, Rattus norvegicus, Apodemus chevrieri, Eothenomys miletus, Niviventer fulvescens, and Mus Pahari. Detection of CoV and HEV was performed by nested-PCR. The infection rate of CoV was 40.74% (11/27) and 2.38% (1/42) in R. norvegicus and R. tanezumi, respectively. The infection rate of HEV was 14.81% (4/27) and 2.38% (1/42) in R. norvegicus and R. tanezumi, respectively. Co-infection with CoV and HEV was detected in two R. norvegicus, with a co-infection rate of 7.41% (2/27). A Basic Local Alignment Search Tool (BLAST) search was performed on partial RNA-dependent RNA polymerase (RdRp) sequences of CoV and HEV. Eleven strains from R. norvegicus were a-CoV, and matched best to strain KY370050 from Rattus losea (Fujian, China), with 99.73% to 99.74% nucleotide (nt) sequency identity. One strain was ss-CoV from R. tanezumi, which displayed 98.21% nt sequence identity with strain MT820632 from Bandicota indica (Yunnan, China). Five strains from R. norvegicus were all HEV-C, and showed 95.87% to 96.21% sequence similarity to strain MN450853 from a patient in Hong Kong, China. In conclusion, CoV and HEV infections are present in rodents in Dali City. Because the host animals of the two viruses are closely related to humans, surveillance and investigations of related viruses should be strengthened.

Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung

Since the outbreak of the new crown pneumonia, the new coronavirus (SARSCoV-2) has been mutating continuously, and it has now become prevalent in more than 200 countries. The cumulative number of confirmed cases in the world has exceeded 460 million, and the number of deaths has exceeded 6 million. The rapid mutation of SARS-CoV-2 highlights the importance of preventive and therapeutic drugs, however, effective therapeutic drugs for new coronary pneumonia are still very scarce. It is still the common goal of scientists from all over the world to develop a safe and effective drug for the treatment of new coronary pneumonia that can inhibit the infection of multiple SARS-CoV-2 mutant strains.

Analysis of intermediate hosts and susceptible animals of SARS-CoV-2 by computational methods

COVID-19, a disease caused by SARS-CoV-2 that produces major symptoms of pneumonia, has been a disaster worldwide. The traceability of SARSCoV- 2 and the discovery of susceptible animal species is crucial to halt viral transmission and explore the mechanism of cross-species transmission. We selected 82 representative ACE2 sequences from the 1000 sequences with the closest homology to the hACE2 protein. All selected ACE2 proteins were subjected to homology modeling. Potential natural and intermediate hosts, as well as animal species susceptible to SARS-CoV-2, were analyzed systematically by calculation of the binding free energy of ACE2 protein to the RBD of SARSCoV- 2. Primates, some wild Felidae, civets, goats, spotted hyenas and golden hamsters are susceptible to SARS-CoV-2 and may be potential intermediate hosts, whereas pangolins, birds and reptiles are unlikely to be intermediate hosts. Mice, rats and guinea pig are not susceptible to SARS-CoV-2. Given their possible susceptibility, non-human primates, goats and golden hamsters could potentially be used as experimental models to examine SARS-CoV-2 infection without transgenesis. Herein, possible candidates for the natural and intermediate hosts of SARS-CoV-2 are suggested, to provide guidance for subsequent studies.

Effects of different mucosal adjuvants on the immune responses induced by porcine deltacoronavirus in mice

Objective: The aim of this study is to screen an ideal adjuvant for an inactivated porcine deltacoronavirus(PDCoV) vaccine to induce mucosal immunity and reduce the side effect of the vaccine. We used different mucosal adjuvants to prepare the inactivated PDCoV vaccines. We then used mouse model to evaluate the humoral, cellular and mucosal immune responses induced by the inactivated vaccines via different immunization routes.