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Spackman, E.

Publications and source records attributed to Spackman, E..

6 recordsLinked to original sources

A systematic review of laboratory investigations into the pathogenesis of avian influenza viruses in wild avifauna of North America

The lack of consolidated information regarding wild bird species response to avian influenza virus (AIV) infection is a challenge for conservation managers, researchers, and related sectors such as public health and commercial poultry. Such information could be used to model complex disease dynamics within communities, prioritize species for surveillance and conservation efforts, or identify species more likely to facilitate spillover into domestic animals or humans. Using two independent searches, we reviewed published literature for studies describing wild bird species experimentally infected with avian influenza to assess host species relative susceptibility to AIVs. Additionally, we summarized broad-scale parameters for elements such as shedding duration and minimum infectious dose that can be used in transmission modeling efforts. Our synthesis documented that waterfowl (i.e., Anatidae) comprise the vast majority of published AIV pathobiology studies, whereas gulls and passerines were less represented in research despite evidence that they also are susceptible and contribute to high pathogenicity avian influenza disease dynamics. This study represents the first comprehensive effort to compile available literature regarding the pathobiology of AIVs in all wild birds in over a decade. This database provides an opportunity to critically examine and assess what is known and identify where further insight is needed.

ecology↗

Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations.

microbiology↗

SGIP1 binding to the α-helical H9 domain of cannabinoid receptor 1 promotes axonal surface expression

Endocannabinoid signalling mediated by cannabinoid type 1 receptors (CB1Rs) is critical for homeostatic neuromodulation of both excitatory and inhibitory synapses. This requires highly polarised axonal surface expression of CB1R, but how this is achieved remains unclear. We previously reported that the H9 domain in the intracellular C-terminus of CB1R contributes to polarised surface expression by an unknown mechanism. Here we show the H9 domain binds to the endocytic adaptor protein SGIP1 to promote CB1R expression in the axonal membrane. Overexpression of SGIP1 increases CB1R axonal surface localisation but has no effect on CB1R lacking the H9 domain (CB1R{Delta}H9). Conversely, SGIP1 knockdown reduces axonal surface expression of CB1R but does not affect CB1R{Delta}H9. Furthermore, SGIP1 knockdown diminishes CB1R-mediated inhibition of presynaptic Ca2+ influx in response to neuronal activity. Together, these data advance mechanistic understanding of endocannabinoid signalling by demonstrating that SGIP1 interaction with H9 underpins axonal CB1R surface expression to regulate presynaptic responsiveness.

neuroscience↗

SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replication in vitro

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is believed to have a zoonotic origin. Bats are a suspected natural host of SARS-CoV-2 because of sequence homology with other bat coronaviruses. Understanding the origin of the virus and determining species susceptibility is essential for managing the transmission potential during a pandemic. In a previous study, we established an in vitro animal model of SARS-CoV-2 susceptibility and replication in a non-permissive avian fibroblast cell line (DF1) based on expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) from different animal species. In this work, we express the ACE2 of seven bat species in DF1 cells and determine their ability to support attachment and replication of the original SARS-CoV-2 Wuhan lineage virus, as well as two variants, Delta and Lambda. We demonstrate that the ACE2 receptor of all seven species: little brown bat (Myotis lucifugus), great roundleaf bat (Hipposideros armiger), Pearsons horseshoe bat (Rhinolophus pearsonii), greater horseshoe bat (Rhinolophus ferrumequinum), Brazilian free-tailed bat (Tadarida brasiliensis), Egyptian rousette (Rousettus aegyptiacus), and Chinese rufous horseshoe bat (Rhinolophus sinicus), made the DF1 cells permissible to the three isolates of SARS-CoV-2. However, the level of virus replication differed between bat species and variant tested. In addition, the Wuhan lineage SARS-CoV-2 virus replicated to higher titers (104.5-105.5 TCID50) than either variant virus (103.5-104.5 TCID50) on pass 1. Interestingly, all viruses tested grew to higher titers (approximately 106 TCID50) when cells expressed the human ACE2 gene compared to bat ACE2. This study provides a practical in vitro method for further testing of animal species for potential susceptibility to current and emerging SARS-CoV-2 viruses.

molecular biology↗

Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells

The SARS-CoV-2 (SC2) virus has caused a worldwide pandemic because of the viruss ability to transmit efficiently human-to-human. A key determinant of infection is the attachment of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Because of the presumed zoonotic origin of SC2, there is no practical way to assess every species susceptibility to SC2 by direct challenge studies. In an effort to have a better predictive model of animal host susceptibility to SC2, we expressed the ACE2 and/or transmembrane serine protease 2 (TMPRSS2) genes from humans and other animal species in the avian fibroblast cell line, DF1, that is not permissive to infection. We demonstrated that expression of both human ACE2 and TMPRSS2 genes is necessary to support SC2 infection and replication in DF1 and a non-permissive sub-lineage of MDCK cells. Titers of SC2 in these cell lines were comparable to those observed in control Vero cells. To further test the model, we developed seven additional transgenic cell lines expressing the ACE2 and TMPRSS2 derived from Felis (cat), Equus (horse), Sus (pig), Capra (goat), Mesocricetus (Golden hamster), Myotis lucifugus (Little Brown bat) and Hipposideros armiger (Great Roundleaf bat) in DF1 cells. Results demonstrate permissive replication of SC2 in cat, Golden hamster, and goat species, but not pig or horse, which correlated with the results of reported challenge studies. The development of this cell culture model allows for more efficient testing of the potential susceptibility of many different animal species for SC2 and emerging variant viruses. IMPORTANCESARS-CoV-2 (SC2) is believed to have originated in animal species and jumped into humans where it has produced the greatest viral pandemic of our time. Identification of animal species susceptible to SC2 infection would provide information on potential zoonotic reservoirs, and transmission potential at the human-animal interface. Our work provides a model system to test the ability of the virus to replicate in an otherwise non-permissive cell line by transgenic insertion of the ACE2 and TMPRSS2 genes from human and other animal species. The results from our in vitro model positively correlate with animal infection studies enhancing the predicative capability of the model. Importantly, we demonstrate that both proteins are required for successful virus replication. These findings establish a framework to test other animal species for susceptibility to infection that may be critical zoonotic reservoirs for transmission, as well as to test variant viruses that arise over time.

microbiology↗

Lack of susceptibility of poultry to SARS-CoV-2 and MERS-CoV

Chickens, turkeys, ducks, quail and geese were challenged with SARS-CoV-2 or MERS-CoV. No disease was observed, no virus replication was detected, and antibodies were not detected in serum. Neither virus replicated in embryonating chickens eggs. Poultry are unlikely to serve a role in the maintenance of either virus.

microbiology↗