Role of Spillover and Spillback in SARS-CoV-2 Transmission and the Importance of One Health in Understanding the Dynamics of the COVID-19 Pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is notable both for its impact on global public health as well as its well-publicized transmissibility to other species of animals. Infection of incidental animal hosts is concerning because of possible emergence of novel variants due to viral mutation. Species that are susceptible to SARS-CoV-2 include domestic and nondomestic cats, domestic dogs, white-tailed deer, mink, and golden hamsters, among others. We detail possible origins of transmission of SARS-CoV-2 to humans, as well as the ecological and molecular mechanisms needed for the virus to establish infection in humans from animals. We highlight examples of SARS-CoV-2 spillover, spillback, and secondary spillover, demonstrating the breadth in the variability of hosts and current transmission events that have been documented in domestic, captive, and wild animals. Lastly, we turn our focus to the importance of animal hosts as potential reservoirs and sources of variant emergence that can have profound effects on the human population. We note that a One Health approach emphasizing surveillance of animals and humans in certain environments using interdisciplinary collaboration is encouraged to manage disease surveillance, regulation on animal trade and testing, and animal vaccine development that will mitigate further disease outbreaks. These efforts will minimize the spread of SARS-CoV-2 and advance knowledge to prevent the spread of future emerging infectious diseases.

Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats.

We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV) and then infected with pathogenic feline immunodeficiency virus (FIV) (co-infection with the host adapted/pathogenic virus) had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4⁺ T cell preservation, greater interferon gamma (IFN-γ) mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases.

Understanding public perceptions of risk regarding outdoor pet cats to inform conservation action.

Free-ranging domestic cats (Felis catus) incur and impose risks on ecosystems and represent a complex issue of critical importance to biodiversity conservation and cat and human health globally. Prior social science research on this topic is limited and has emphasized feral cats even though owned cats often comprise a large proportion of the outdoor cat population, particularly in urban areas. To address this gap, we examined public risk perceptions and attitudes toward outdoor pet cats across varying levels of urbanization, including along the wildland-urban interface, in Colorado (U.S.A.), through a mail survey of 1397 residents. Residents did not view all types of risks uniformly. They viewed risks of cat predation on wildlife and carnivore predation on cats as more likely than disease-related risks. Additionally, risk perceptions were related to attitudes, prior experiences with cats and cat-wildlife interactions, and cat-owner behavior. Our findings suggest that changes in risk perceptions may result in behavior change. Therefore, knowledge of cat-related risk perceptions and attitudes could be used to develop communication programs aimed at promoting risk-aversive behaviors among cat owners and cat-management strategies that are acceptable to the public and that directly advance the conservation of native species.

Strain-specific viral distribution and neuropathology of feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV(PPR) (PPR, relatively apathogenic but associated with neurologic manifestations), FIV(C36) (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36 genomic elements contribute to viral replication characteristics, and (ii) 5' PPR genomic elements contribute to CNS manifestations. This study illustrates the potential for FIV to provide valuable information about neuroAIDS pathogenesis related to genotype and viral kinetics, as well as to identify strains useful to evaluation of therapeutic intervention.

Disparities in ammonia, temperature, humidity, and airborne particulate matter between the micro-and macroenvironments of mice in individually ventilated caging.

Animal room environmental parameters typically are monitored with the assumption that the environment within the cage closely mirrors the room environment. This study evaluated that premise by examining macro- (room) and microenvironmental (cage) parameters in individually ventilated cages housing mice with variable amounts of bedding over a period of 17 d without cage changes. Intracage ammonia levels remained within recommended human guidelines but were higher than room levels, confirming that microisolation caging is efficient at preventing ammonia generated from animal waste from escaping into the room. Humidity and temperature within cages were consistently higher than room levels. Particles in the room predominantly consisted of fine particles (diameter less than 2.5 mum), presumably from the ambient atmosphere; some of these particles were found in the cage microenvironment. In addition, mouse activity within cages produced larger particles, and these particles contributed to substantially higher aerosol mass concentrations within the cage. These findings demonstrate that, although cage and room environmental parameters differ, knowledge of room environmental conditions can be used to predict certain conditions within the cage. This association is relevant in that typical animal care standard operating procedures rely on room measurements, not intracage measurements, which arguably are more important for assessing animal welfare. Further, location and ambient climate can influence particle concentrations in the room, and consequently within the animal cage, suggesting local weather patterns and air quality may account for variability among studies conducted at sites that are geographically divergent.

Effects of cage-change frequency and bedding volume on mice and their microenvironment.

The frequency at which mouse cages are changed has important implications for the animals, animal care personnel, and facility managers. The objective of this study was to determine how bedding volume and the interval between changes affect microenvironmental conditions, health, and behavior of mice housed in individually ventilated cages (IVC). A total of 15 cages (n = 5 cages per bedding volume) housing ICR female mice (n = 5 animals per cage) were monitored for 17 d. Parameters monitored included clinical evaluation of each animal, appearance of the cage, fecal corticosterone levels, bedding weight, and mouse mass. Atmospheric analysis was performed daily to determine intracage ammonia cage humidity and temperature on a daily basis. Mice were videotaped for 10 min on days 1, 8, and 15, and videos were analyzed for abnormal behaviors. On day 17, 1 mouse from each cage was euthanized, and bronchoalveolar lavage was performed. Statistical differences in parameters were most often noted between low- and high-volume bedding groups. Correlation between visual appearance and actual intracage environmental conditions and mouse health and behavior at specific time points indicated cages that appear dirty to most observers did not have measurably adverse effects on the animals for any of the many parameters evaluated in this study. This study demonstrated that a 2-wk interval between cage changes for ICR female mice housed in IVC caging (with approximately 90 air changes per hour) and aspen chip bedding did not significantly affect measures of animal well-being in this study. This lack of effect occurred despite the appearance of excessive soiling by the 2-wk time point.