Publications by authors named "Bridgett Sharp"

12 Publications

  • Page 1 of 1

Evidence of influenza infection in dogs and cats in central Chile.

Prev Vet Med 2021 Apr 16;191:105349. Epub 2021 Apr 16.

Department of Preventive Animal Medicine, Faculty of Veterinary Sciences, University of Chile, Santiago, Chile. Electronic address:

As companion animals, dogs and cats live in close contact with humans, generating the possibility of interspecies pathogen transmission events. Equine origin H3N8 and avian origin H5N1 influenza virus have been reported in dogs and cats respectively since 2004 with outbreaks associated with different strains recorded for both species in Asia and North America. To date, there have been no reports of influenza viruses from companion animals in South America. To fill this gap in knowledge, we performed active epidemiological surveillance in shelters that received abandoned animals, backyard production systems and veterinary clinics between May 2017 and January 2019 to estimate the burden of influenza infection in cats and dogs in the central region of Chile. Blood samples, oropharyngeal swabs or both were collected for influenza A virus detection by RT-qPCR, NP-ELISA, and hemagglutination inhibition assay. Logistic regression models were performed to assess the association between NP-ELISA-positivity and variables including sex and animal origin. The percentage of ELISA-positive samples was 43.5 % (95 % CI: 37.0-50.1) and 23.3 % (95 % CI: 10.6-42.7) for dogs and cats, respectively. No association was found between NP-ELISA results and sex or animal origin for either dogs or cats. Two ELISA positive samples showed hemagglutination inhibition titers against pandemic H1N1 influenza. One dog sample tested positive by RT-qPCR, indicating an overall RT-qPCR positivity in dogs of 1.1 % (95 % CI: 0.05-6.7). None of the tested cat samples were positive by this assay.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105349DOI Listing
April 2021

Equine-Like H3 Avian Influenza Viruses in Wild Birds, Chile.

Emerg Infect Dis 2020 12;26(12):2887-2898

Since their discovery in the United States in 1963, outbreaks of infection with equine influenza virus (H3N8) have been associated with serious respiratory disease in horses worldwide. Genomic analysis suggests that equine H3 viruses are of an avian lineage, likely originating in wild birds. Equine-like internal genes have been identified in avian influenza viruses isolated from wild birds in the Southern Cone of South America. However, an equine-like H3 hemagglutinin has not been identified. We isolated 6 distinct H3 viruses from wild birds in Chile that have hemagglutinin, nucleoprotein, nonstructural protein 1, and polymerase acidic genes with high nucleotide homology to the 1963 H3N8 equine influenza virus lineage. Despite the nucleotide similarity, viruses from Chile were antigenically more closely related to avian viruses and transmitted effectively in chickens, suggesting adaptation to the avian host. These studies provide the initial demonstration that equine-like H3 hemagglutinin continues to circulate in a wild bird reservoir.
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http://dx.doi.org/10.3201/eid2612.202063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706983PMC
December 2020

Astrovirus infects actively secreting goblet cells and alters the gut mucus barrier.

Nat Commun 2020 04 29;11(1):2097. Epub 2020 Apr 29.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.

Astroviruses are a global cause of pediatric diarrhea, but they are largely understudied, and it is unclear how and where they replicate in the gut. Using an in vivo model, here we report that murine astrovirus preferentially infects actively secreting small intestinal goblet cells, specialized epithelial cells that maintain the mucus barrier. Consequently, virus infection alters mucus production, leading to an increase in mucus-associated bacteria and resistance to enteropathogenic E. coli colonization. These studies establish the main target cell type and region of the gut for productive murine astrovirus infection. They further define a mechanism by which an enteric virus can regulate the mucus barrier, induce functional changes to commensal microbial communities, and alter host susceptibility to pathogenic bacteria.
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http://dx.doi.org/10.1038/s41467-020-15999-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190700PMC
April 2020

Characterizing Emerging Canine H3 Influenza Viruses.

PLoS Pathog 2020 04 14;16(4):e1008409. Epub 2020 Apr 14.

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.
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http://dx.doi.org/10.1371/journal.ppat.1008409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182277PMC
April 2020

Astrovirus Replication Is Inhibited by Nitazoxanide and .

J Virol 2020 02 14;94(5). Epub 2020 Feb 14.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

Astroviruses (AstV) are a leading cause of diarrhea, especially in the very young, the elderly, and immunocompromised populations. Despite their significant impact on public health, no drug therapies for astrovirus have been identified. In this study, we fill this gap in knowledge and demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replication with a 50% effective concentration (EC) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding , exhibiting its potential as a future clinical therapeutic. Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial diarrhea cases in children worldwide. HAstV infection can be especially problematic in immunocompromised people and infants, where the virus has been associated with necrotizing enterocolitis and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And yet, no antivirals have been identified to treat astrovirus infection. Our study provides the first evidence that nitazoxanide may be an effective therapeutic strategy against astrovirus disease.
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http://dx.doi.org/10.1128/JVI.01706-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022343PMC
February 2020

Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice.

J Virol 2019 07 14;93(13). Epub 2019 Jun 14.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

Human astroviruses are single-stranded RNA enteric viruses that cause a spectrum of disease ranging from asymptomatic infection to systemic extragastrointestinal spread; however, they are among the least-characterized enteric viruses, and there is a lack of a well-characterized small animal model. Finding that immunocompromised mice were resistant to human astrovirus infection via multiple routes of inoculation, our studies aimed to determine whether murine astrovirus (MuAstV) could be used to model human astrovirus disease. We experimentally infected wild-type mice with MuAstV isolated from immunocompromised mice and found that the virus was detected throughout the gastrointestinal tract, including the stomach, but was not associated with diarrhea. The virus was also detected in the lung. Although virus levels were higher in recently weaned mice, the levels were similar in male and female adult mice. Using two distinct viruses isolated from different immunocompromised mouse strains, we observed virus strain-specific differences in the duration of infection (3 versus 10 weeks) in wild-type mice, indicating that the within-host immune pressure from donor mice shaped the virus kinetics in immunocompetent recipient hosts. Both virus strains elicited minimal pathology and a lack of sustained immunity. In summary, MuAstV represents a useful model for studying asymptomatic human infection and gaining insight into the astrovirus pathogenesis and immunity. Astroviruses are widespread in both birds and mammals; however, little is known about the pathogenesis and the immune response to the virus due to the lack of a well-characterized small-animal model. Here we describe two distinct strains of murine astrovirus that cause infections in immunocompetent mice that mirror aspects of asymptomatic human infections, including minimal pathology and short-lived immunity. However, we noted that the duration of infection differed greatly between the strains, highlighting an important facet of these viruses that was not previously appreciated. The ubiquitous nature and diversity of murine astroviruses coupled with the continuous likelihood of reinfection raise the possibility of viral interference with other mouse models of disease.
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http://dx.doi.org/10.1128/JVI.00223-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580942PMC
July 2019

Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ.

Nat Microbiol 2019 07 1;4(7):1120-1128. Epub 2019 Apr 1.

Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.

Commensal microbes profoundly impact host immunity to enteric viral infections. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.
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http://dx.doi.org/10.1038/s41564-019-0416-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588490PMC
July 2019

Wild birds in Chile Harbor diverse avian influenza A viruses.

Emerg Microbes Infect 2018 Mar 29;7(1):44. Epub 2018 Mar 29.

St Jude Children's Research Hospital, Memphis, TN, 38105, USA.

While the circulation of avian influenza viruses (IAV) in wild birds in the northern hemisphere has been well documented, data from South America remain sparse. To address this gap in knowledge, we undertook IAV surveillance in wild birds in parts of Central and Northern Chile between 2012 and 2015. A wide diversity of hemagglutinin (HA) and neuraminidase (NA) subtypes were identified and 16 viruses were isolated including low pathogenic H5 and H7 strains, making this the largest and most diverse collection of Chilean avian IAVs to date. Unlike IAVs isolated from wild birds in other South American countries where the genes were most like viruses isolated from wild birds in either North America or South America, the Chilean viruses were reassortants containing genes like viruses isolated from both continents. In summary, our studies demonstrate that genetically diverse avian IAVs are circulating in wild birds in Chile highlighting the need for further investigation in this understudied area of the world.
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http://dx.doi.org/10.1038/s41426-018-0046-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874252PMC
March 2018

Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis.

NPJ Parkinsons Dis 2017 23;3:18. Epub 2017 May 23.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place,, Memphis, TN 38105 USA.

Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson's disease (Ransohoff, Science 353: 777-783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493-514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131-158, 2013) could synergize with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Jackson-Lewis et al. in Mark LeDoux (ed) : 287-306, Elsevier, 2015) to induce a greater microglial activation and loss of substantia nigra pars compacta dopaminergic neurons than either insult alone. H1N1-infected animals administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exhibit a 20% greater loss of substantia nigra pars compacta dopaminergic neurons than occurs from the additive effects of H1N1 or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone ( < 0.001). No synergistic effects were found in microglial activation. The synergistic dopaminergic neuron loss is eliminated by influenza vaccination or treatment with oseltamivir carboxylate. This work shows that multiple insults can induce synergistic effects; and even these small changes can be significant as it might allow one to cross a phenotypic disease threshold that would not occur from individual non-interacting exposures. Our observations also have important implications for public health, providing impetus for influenza vaccination or prompt treatment with anti-viral medications upon influenza diagnosis.
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http://dx.doi.org/10.1038/s41531-017-0019-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460228PMC
May 2017

Pandemic Seasonal H1N1 Reassortants Recovered from Patient Material Display a Phenotype Similar to That of the Seasonal Parent.

J Virol 2016 09 12;90(17):7647-56. Epub 2016 Aug 12.

St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Unlabelled: We have previously shown that 11 patients became naturally coinfected with seasonal H1N1 (A/H1N1) and pandemic H1N1 (pdm/H1N1) during the Southern hemisphere winter of 2009 in New Zealand. Reassortment of influenza A viruses is readily observed during coinfection of host animals and in vitro; however, reports of reassortment occurring naturally in humans are rare. Using clinical specimen material, we show reassortment between the two coinfecting viruses occurred with high likelihood directly in one of the previously identified patients. Despite the lack of spread of these reassortants in the community, we did not find them to be attenuated in several model systems for viral replication and virus transmission: multistep growth curves in differentiated human bronchial epithelial cells revealed no growth deficiency in six recovered reassortants compared to A/H1N1 and pdm/H1N1 isolates. Two reassortant viruses were assessed in ferrets and showed transmission to aerosol contacts. This study demonstrates that influenza virus reassortants can arise in naturally coinfected patients.

Importance: Reassortment of influenza A viruses is an important driver of virus evolution, but little has been done to address humans as hosts for the generation of novel influenza viruses. We show here that multiple reassortant viruses were generated during natural coinfection of a patient with pandemic H1N1 (2009) and seasonal H1N1 influenza A viruses. Though apparently fit in model systems, these reassortants did not become established in the wider population, presumably due to herd immunity against their seasonal H1 antigen.
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http://dx.doi.org/10.1128/JVI.00772-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988147PMC
September 2016

Type I Interferon Response Limits Astrovirus Replication and Protects against Increased Barrier Permeability In Vitro and In Vivo.

J Virol 2016 02 9;90(4):1988-96. Epub 2015 Dec 9.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

Unlabelled: Little is known about intrinsic epithelial cell responses against astrovirus infection. Here we show that human astrovirus type 1 (HAstV-1) infection induces type I interferon (beta interferon [IFN-β]) production in differentiated Caco2 cells, which not only inhibits viral replication by blocking positive-strand viral RNA and capsid protein synthesis but also protects against HAstV-1-increased barrier permeability. Excitingly, we found similar results in vivo using a murine astrovirus (MuAstV) model, providing new evidence that virus-induced type I IFNs may protect against astrovirus replication and pathogenesis in vivo.

Importance: Human astroviruses are a major cause of pediatric diarrhea, yet little is known about the immune response. Here we show that type I interferon limits astrovirus infection and preserves barrier permeability both in vitro and in vivo. Importantly, we characterized a new mouse model for studying astrovirus replication and pathogenesis.
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http://dx.doi.org/10.1128/JVI.02367-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733991PMC
February 2016

Surveillance for influenza viruses in poultry and swine, west Africa, 2006-2008.

Emerg Infect Dis 2012 Sep;18(9):1446-52

Central Laboratory for Animal Diseases, Bingerville, Côte d'Ivoire.

To determine the extent of animal influenza virus circulation in Côte d'Ivoire, Benin, and Togo, we initiated systematic year-round active influenza surveillance in backyard birds (predominantly chickens, guinea fowl, and ducks) and pigs. A total of 26,746 swab specimens were screened by using reverse transcription PCR. Animal influenza prevalence was estimated at 0 (95% CIs for each of the 2 study years 0-0.04% to 0-1.48% [birds] and 0-0.28% to 0-5% [pigs]). In addition, 2,276 serum samples from the same populations were negative for influenza-specific antibodies. These data indicate that the environments and host populations previously identified as harboring high levels of influenza virus in Southeast Asia do not do so in these 3 countries. The combination of climate and animal density factors might be responsible for what appears to be the absence of influenza virus in the backyard sector of the 3 countries.
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http://dx.doi.org/10.3201/eid1809.111296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437700PMC
September 2012