Browsing by Author "Crossland, Nicholas A."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    FeMV is a cathepsin-dependent unique morbillivirus infecting the kidneys of domestic cats
    (National Academy of Sciences, 2022) Nambulli, Sham; Rennick, Linda J.; Acciardo, Andrew S.; Tilston-Lunel, Natasha L.; Ho, Gregory; Crossland, Nicholas A.; Hardcastle, Kathy; Nieto, Betsy; Bainbridge, Graeme; Williams, Tracey; Sharp, Claire R.; Duprex, W. Paul; Microbiology and Immunology, School of Medicine
    Feline morbillivirus (FeMV) has been classified as a morbillivirus despite lacking several biological features shared by all other known viruses in the genus. We confirm that FeMV uses CD150 as a cellular receptor and employs a different protease to furin to process the fusion glycoprotein. As such, FeMV may represent an important evolutionary intermediate between morbilliviruses and the zoonotic henipaviruses. Feline chronic kidney disease is the leading cause of morbidity and mortality in cats and has no clear etiology. FeMV has been postulated to be a causative agent. We dissected FeMV pathogenesis using recombinant, fluorescent protein expressing viruses based on an unpassaged clinical isolate. This sheds light on the primary target cells infected and possible mechanisms of host-to-host transmission.
  • Thumbnail Image
    Item
    Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses
    (American Association for the Advancement of Science, 2021-05-26) Nambulli, Sham; Xiang, Yufei; Tilston-Lunel, Natasha L.; Rennick, Linda J.; Sang, Zhe; Klimstra, William B.; Reed, Douglas S.; Crossland, Nicholas A.; Shi, Yi; Duprex, W. Paul; Microbiology and Immunology, School of Medicine
    Globally, there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate to severe COVID-19 disease, we demonstrate the high efficacy of PiN-21 to prevent and treat SARS-CoV-2 infection. Intranasal delivery of PiN-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduces viral burdens in both lower and upper airways compared to control. Aerosol delivery of PiN-21 facilitates deposition throughout the respiratory tract and dose minimization to 0.2 mg/kg. Inhalation treatment quickly reverses animals' weight loss after infection, decreases lung viral titers by 6 logs leading to drastically mitigated lung pathology, and prevents viral pneumonia. Combined with the marked stability and low production cost, this innovative therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.