Browsing by Author "Albrecht, Randy A."

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    Glycosylations in the Globular Head of the Hemagglutinin Protein Modulate the Virulence and Antigenic Properties of the H1N1 Influenza Viruses
    (2013) Medina, Rafael; Stertz, Silke; Manicassamy, Balaji; Zimmermann, Petra; Sun, Xiangjie; Albrecht, Randy A.; Uusi-Kerttula, Hanni; Zagordi, Osvaldo; Belshe, Robert B.; Frey, Sharon E.; Tumpey, Terrence M.; García Sastre, Adolfo
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    Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection
    (2020) Kau, Drishti; Rathnasinghe, Raveen Shevantha; Ferrés, Marcela; Tan, Gene S.; Barrera Vásquez, Aldo Vincent; Pickett, Brett E.; Methe, Barbara A.; Das, Suman; Budnik Ojeda, Isolda Cecilia; Halpin, Rebecca A.; Wentworth, David; Schmolke, Mirco; Mena, Ignacio; Albrecht, Randy A.; Singh, Indresh; Nelson, Karen E.; Garcia Sastre, Adolfo; Dupont, Chris L.; Medina, Rafael
    Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation. The effects of influenza infection on the upper respiratory tract (URT) microbiome are largely unknown. Here, we report a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes have stable healthy ecostate communities both within and between individuals. In contrast, infected patients and ferrets exhibit large changes in bacterial community composition over time and between individuals. The unhealthy ecostates of infected individuals progress towards the healthy ecostate, coinciding with viral clearance and recovery. Pseudomonadales associate statistically with the disturbed microbiomes of infected individuals. The dynamic and resilient microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections. Influenza A virus (IAV) infection can be exacerbated by bacterial co-infections but the effect of IAV on the upper respiratory tract (URT) microbiome remains unclear. Here, the authors compare the dynamics of the UTR microbiome in IAV-infected ferrets and humans, finding similar trends at the ecosystem and individual taxon level in both hosts.
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    TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation
    (2021) Ho, Jessica Sook Yuin; Mok, Bobo Wing-Yee; Campisi, Laura; Jordan, Tristan; Yildiz, Soner; Parameswaran, Sreeja; Wayman, Joseph A.; Gaudreault, Natasha N.; Meekins, David A.; Indran, Sabarish, V; Morozov, Igor; Trujillo, Jessie D.; Fstkchyan, Yesai S.; Rathnasinghe, Raveen; Zhu, Zeyu; Zheng, Simin; Zhao, Nan; White, Kris; Ray-Jones, Helen; Malysheva, Valeriya; Thiecke, Michiel J.; Lau, Siu-Ying; Liu, Honglian; Zhang, Anna Junxia; Lee, Andrew Chak-Yiu; Liu, Wen-Chun; Jangra, Sonia; Escalera, Alba; Aydillo, Teresa; Melo, Betsaida Salom; Guccione, Ernesto; Sebra, Robert; Shum, Elaine; Bakker, Jan; Kaufman, David A.; Moreira, Andre L.; Carossino, Mariano; Balasuriya, Udeni B. R.; Byun, Minji; Albrecht, Randy A.; Schotsaert, Michael; Garcia-Sastre, Adolfo; Chanda, Sumit K.; Miraldi, Emily R.; Jeyasekharan, Anand D.; TenOever, Benjamin R.; Spivakov, Mikhail; Weirauch, Matthew T.; Heinz, Sven; Chen, Honglin; Benner, Christopher; Richt, Juergen A.; Marazzi, Ivan
    The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans.