Document text
Principal Investigator: Adam Lee Bailey
Organization: UNIVERSITY OF WISCONSIN-MADISON
Fiscal Year: 2024
Award: $243,505
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
As COVID-19 has illustrated, the emergence of novel RNA viruses from wild animals poses a significant threat
to human health. In this proposal, we will begin to assess the zoonotic potential of an entire family of viruses:
the arteriviruses. The arteriviruses are the only mammalian RNA virus family not known to infect humans; as
such they have been largely ignored by the biomedical research community. However, these viruses cause
severe disease in many other mammals including monkeys. Due to historical neglect, the research community
has not developed the resources and knowledge that would be required to rapidly develop medical
countermeasures in the event of an arterivirus emergence in humans. Thus, these viruses are uniquely
positioned in our pandemic preparedness blindspot. In this project we will characterize the zoonotic risk posed
by arteriviruses using a diverse collection of arteriviruses and variety of host tools. In Aim 1, we will build upon
our recent discoveries that identified CD163 as a host molecule required for arterivirus entry into cells. We will
create a panel of cells expressing CD163 orthologs from various species (human, monkey, mouse, pig) and
examine the susceptibility of these cells to a panel of arteriviruses. Next, we will create CD163 molecules with
mutations and deletions to map the key domains and residues required for arterivirus binding. Finally, we will
use our knowledge of CD163 to try and grow novel arterivirus isolates that so far cannot be grown in culture. In
Aim 2, we will build upon our recent discovery that the neonatal Fc receptor (FcRn) is required for arterivirus
infection of cells. We hypothesize that FcRn acts as an attachment factor, allowing the virus to adhere to the
cell surface and become internalized in the endosomal compartment where it contacts CD163. To test this, we
will perform a series of binding and internalization assays (in the presence and absence of CD163) to establish
a role of FcRn as a pan-arterivirus attachment factor. We will also overexpress CD163 and FcRn in the
background of FcRn- and CD163-knockout cells to determine if these molecules are each required in
sequential fashion or are redundant for arterivirus infection. Finally, we will perform a pair-wise species
comparison of FcRn orthologs and divergent arteriviruses to examine whether FcRn acts as a barrier to
cross-species infection. Upon conclusion of this project we will have a greater appreciation for the zoonotic risk
posed by these viruses. We will also have developed tools, biological systems, and knowledge that will serve
as a critical resource for the rapid development of life-saving medical countermeasures in the event of an
arterivirus outbreak in humans.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Air><Animals><Arteriviridae><Arterivirus><Arterivirus Infections><Assay><Binding><Bioassay><Biological><Biological Assay><Biology><Biomedical Research><Blind Spots><Bypass><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 virus><COVID-19 years><COVID19 virus><CRISPR><CRISPR/Cas system><CV-19><Cell Body><Cell surface><Cells><Cellular Membrane><Chromosome Mapping><Clustered Regularly Interspaced Short Palindromic Repeats><CoV-2><CoV2><Collection><Communities><Complex><Coronaviridae><Coronavirus><Coronavirus Infectious Disease 2019><Development><Diagnostic><Disease><Disease Outbreaks><Disorder><Distant><Domestic Animals><Domestic Horse><Endosomes><Equine><Equine Species><Equus caballus><Equus przewalskii><Event><Family><Family suidae><Fc Receptor><FcRn><FcRn neonatal transfer protein><Food Supply><Foundations><Future><Gene Localization><Gene Mapping><Gene Mapping Genetics><Gene Proteins><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Diversity><Genetic Variation><Genetic defect><Health><Horses><Host Factor><Host Factor Protein><Human><Infection><Integration Host Factors><Intervention><Intervention Strategies><Investments><Knock-out><Knockout><Knowledge><Leanness><Life><Life Cycle><Life Cycle Stages><Linkage Mapping><Mammalia><Mammals><Maps><Mediating><Mice><Mice Mammals><Modern Man><Molecular><Molecular Interaction><Monkey Hemorrhagic Disease Virus><Monkeys><Murine><Mus><Mutation><Ortholog><Orthologous Gene><Outbreaks><Pathogenesis><Personal Satisfaction><Pigs><Position><Positioning Attribute><Predisposition><Primates><Primates Mammals><Property><Protein Gene Products><RNA Viruses><Receptor Protein><Receptosomes><Research><Research Resources><Resources><Retinal blind spot><Risk><Risk Assessment><Rodent><Rodentia><Rodents Mammals><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Series><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Simian Hemorrhagic Disease Virus><Simian hemorrhagic fever virus><Suidae><Susceptibility><Swine><System><Testing><Therapeutic><Thinness><Total Human and Non-Human Gene Mapping><Vaccines><Variant><Variation><Viral><Viral Diseases><Viral Receptor><Virion><Virus><Virus Diseases><Virus Particle><Virus Receptors><Wild Animals><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><antibody receptor><biologic><biological systems><combat><corona virus><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><coronavirus infectious disease-19><developmental><domesticated animal><experiment><experimental research><experimental study><experiments><genetic mapping><genome mutation><genome scale><genome-wide><genomewide><hCoV19><improved><interventional strategy><life course><medical countermeasure><nCoV2><neglect><neonatal Fc receptor><non-human primate><nonhuman primate><novel><novel virus><overexpress><overexpression><pandemic disease preparedness><pandemic planning><pandemic preparedness><pandemic readiness><particle><permissiveness><porcine><programs><receptor><receptor function><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><skills><social role><suid><technology platform><technology system><tool><viral infection><virus infection><virus-induced disease><well-being><wellbeing>