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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in humans, has a broad host range, and is able to infect domestic and wild animal species. Notably, white-tailed deer (WTD, Odocoileus virginianus ), the most widely distributed cervid species in the Americas, were shown to be highly susceptible to SARS-CoV-2 in challenge studies and reported natural infection/exposure rates approaching 30–40% in free-ranging WTD in the U.S. Thus, understanding the infection and transmission dynamics of SARS-CoV-2 in WTD is critical to prevent future zoonotic transmission to humans, at the human-WTD interface during hunting or venison farming, and for implementation of effective disease control measures. Here, we demonstrated that following intranasal inoculation with SARS-CoV-2 B.1 lineage, WTD fawns (~8-month-old) shed infectious virus up to day 5 post-inoculation (pi), with high viral loads shed in nasal and oral secretions. This resulted in efficient deer-to-deer transmission on day 3 pi. Consistent a with lack of infectious SARS-CoV-2 shedding after day 5 pi, no transmission was observed to contact animals added on days 6 and 9 pi. We have also investigated the tropism and sites of SARS-CoV-2 replication in adult WTD (3–4 years of age). Infectious virus was detected up to day 6 pi in nasal secretions, and from various respiratory-, lymphoid-, and central nervous system tissues, indicating broad tissue tropism and multiple sites of virus replication. The study provides important insights on the infection and transmission dynamics of SARS-CoV-2 in WTD, a wild animal species that is highly susceptible to infection and with the potential to become a reservoir for the virus in the field.

White-tailed deer ( Odocoileus virginianus ) have emerged as a reservoir host for SARS-CoV-2 given their susceptibility to infection and demonstrated high rates of seroprevalence and infection across the United States. As SARS-CoV-2 circulates within free-ranging white-tailed deer populations, there is the risk of transmission to other wildlife species and even back to the human population. The goal of this study was to determine the susceptibility, shedding, and immune response of North American elk ( Cervus elaphus canadensis ) to experimental infection with SARS-CoV-2, to determine if another wide-ranging cervid species could potentially serve as a reservoir host for the virus. Here we demonstrate that while North American elk do not develop clinical signs of disease, they do develop a neutralizing antibody response to infection, suggesting the virus is capable of replicating in this mammalian host. Additionally, we demonstrate SARS-CoV-2 RNA presence in the medial retropharyngeal lymph nodes of infected elk three weeks after experimental infection. Consistent with previous observations in humans, these data may highlight a mechanism of viral persistence for SARS-CoV-2 in elk.

We have investigated the pharmacokinetics of TunR2, a modified tunicamycin-type antibiotic, in mice and cattle. TunR2 has previously been shown to be effective in a mycobacterial disease model using zebrafish, with a minimal activation of the eukaryotic unfolded protein response ( upr ) and a reduction in the in vivo mycobacterial burden. In this study, we presented statistically relevant pharmacokinetics of native tunicamycin (Tun) and two less toxic modified analogs, TunR2 and TunR1, using a well-defined clonal C57BL/6 mouse (both male and female). Blood samples were collected at multiple time points, and plasma concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated using a two-compartment analysis. Our findings indicate that Tun and TunR1 tend to distribute in tissue compared to TunR2, which has a longer half-life than Tun. This translates into longer TunR2 activity time, potentially allowing for less frequent dosing than Tun or TunR1. We subsequently administered the modified TunR2 to Holstein cattle using a three-bolus intravenous regimen. We monitored blood, milk, urine, and feces over 90 days. In dairy cattle, the pharmacokinetics of TunR2 appear to be cumulative, and clear after 10 days. These findings provide critical new insights into the pharmacokinetics of TunR2. We concluded that TunR2 has considerable potential for treating bacterial infections, particularly as an antimicrobial adjuvant with well-established β-lactam antibiotics. Further studies are required to study safety and optimize dosing regimens for effective therapeutic use, as well as in combination with other antibiotics, such as β-lactams.

White-tailed deer are susceptible to scrapie (WTD scrapie) after oronasal inoculation with the classical scrapie agent from sheep. Deer affected by WTD scrapie are difficult to differentiate from deer infected with chronic wasting disease (CWD). To assess the transmissibility of the WTD scrapie agent and tissue phenotypes when further passaged in white-tailed deer, we oronasally inoculated wild-type white-tailed deer with WTD scrapie agent. We found that WTD scrapie and CWD agents were generally similar, although some differences were noted. The greatest differences were seen in bioassays of cervidized mice that exhibited significantly longer survival periods when inoculated with WTD scrapie agent than those inoculated with CWD agent. Our findings establish that white-tailed deer are susceptible to WTD scrapie and that the presence of WTD scrapie agent in the lymphoreticular system suggests the handling of suspected cases should be consistent with current CWD guidelines because environmental shedding may occur.

Scrapie, a prion disease of sheep, is highly resistant to conventional deactivation. Numerous methods to deactivate scrapie have been tested in laboratory animal models, and adequate autoclave treatment can reduce or remove the infectivity of some classical scrapie strains depending on the heating parameters used. In this study, we autoclaved brain homogenate from a sheep with US scrapie strain 13–7 for 30 minutes at 121°C. Genetically susceptible VRQ/ARQ sheep were orally inoculated with 3 grams of the autoclaved brain homogenate. For comparison, a second group of sheep was inoculated with a non-autoclaved brain homogenate. Rectal biopsies were used to assess antemortem scrapie disease progression throughout the study. Five out of ten (5/10) sheep that received autoclaved inoculum ultimately developed scrapie after an experimental endpoint of 72 months. These sheep had a mean incubation period of 26.99 months. Two out of five (2/5) positive sheep had detectable PrP Sc in antemortem rectal biopsies, and two (2/5) other sheep had PrP Sc in postmortem rectal tissue. A single sheep (1/5) was positive for scrapie in the CNS, small intestine, and retropharyngeal lymph node but had negative rectal tissue. All of the sheep (10/10) that received non-autoclaved inoculum developed scrapie with a mean incubation period of 20.2 months and had positive rectal biopsies at the earliest timepoint (14.7 months post-inoculation). These results demonstrate that sheep are orally susceptible to US derived classical scrapie strain 13–7 after autoclave treatment at 121°C for 30 minutes. Differences in incubation periods and time interval to first positive rectal biopsies indicate a partial reduction in infectivity titers for the autoclaved inoculum group.

Scrapie is a transmissible spongiform encephalopathy that occurs in sheep. Atypical/Nor98 scrapie occurs in sheep that tend to be resistant to classical scrapie and it is thought to occur spontaneously. The purpose of this study was to test the transmission of the Atypical/Nor98 scrapie agent in three genotypes of Suffolk sheep and characterize the distribution of misfolded prion protein (PrP Sc ). Ten sheep were intracranially inoculated with brain homogenate from a sheep with Atypical/Nor98 scrapie. All sheep with the ARQ/ARQ and ARQ/ARR genotypes developed Atypical/Nor98 scrapie confirmed by immunohistochemistry, and one sheep with the VRQ/ARQ genotype had detectable PrP Sc consistent with Atypical/Nor98 scrapie at the experimental endpoint of 8 years. Sheep with mild early accumulations of PrP Sc in the cerebellum had concomitant retinal PrP Sc . Accordingly, large amounts of retinal PrP Sc were identified in clinically affected sheep and sheep with dense accumulations of PrP Sc in the cerebellum.

Chronic wasting disease (CWD) is a fatal prion disease of cervids. We examined host range of CWD by oronasally inoculating Suffolk sheep with brain homogenate from a CWD-positive white-tailed deer. Sixty months after inoculation, 1/7 sheep had immunoreactivity against the misfolded form of prion protein in lymphoid tissue. Results were confirmed by mouse bioassay.

Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrPSc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals' scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a health risk for humans and other domestic and wildlife species. Recently, North American elk have been identified as seropositive for SARS-CoV-2, thus posing a potential threat to humans and other mammals. In this work, we characterized the peripheral transcriptomic response to experimental SARS-CoV-2 infection in calves and adult elk at different time points. Results Significantly differentially expressed genes were identified at 2-, 5-, and 14-days post inoculation (pi) for both age groups. Adult elk presented the greatest number of differentially expressed (DE) genes at all time points, including many genes associated with viral response, immune activation, antibody production, as well as genes associated with coronavirus disease (COVID-19), and coronavirus GO terms and KEGG pathways. Calves presented DE genes associated with viral responses at 5 days pi as well as neurodegenerative-associated genes at 14 days pi. Both adults and calves showed predicted activation of the ISGF3 and IFN type I pathways at day 2 pi and, globally, increased activity related to the coronavirus pathway disease at 5 and 14 days pi. Conclusions Collectively, this work provides valuable data characterizing the cervid immune response of elk to viral diseases as well as the response of wildlife to SARS-CoV-2 infection.

The COVID-19 pandemic represents one of the most significant public health events of the last century. As with other coronaviruses (SARS, MERS) the role of animals is of intense interest. Believed to have originated in bats, the role of other animals in the epidemiology of the SARS-CoV-2 pandemic is still unclear, as is the range of susceptible hosts. American bison were intranasally infected with SARS-CoV-2 and monitored for seroconversion and the presence of viral RNA in oronasal secretions and feces. Although clinical signs were not seen, permissiveness of bison to infection with SARS-CoV-2 was manifest by seroconversion, the presence of viral RNA in oronasal secretions, persistence of viral RNA in lymphoid tissue, and viral associated interstitial pneumonia. Retrospective sequencing of the inoculum revealed a common in vitro adaptation in the furin cleavage site of the spike protein that may have reduced in vivo viral fitness. As such, we cannot exclude the possibility that use of an isolate with an intact furin cleavage motif would more efficiently infect bison.