Browsing by Author "Rathnasinghe, Raveen"

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    Novel influenza A viruses in pigs with zoonotic potential, Chile
    (2024) Tapia, Rodrigo; Brito, Barbara; Saavedra, Marco; Mena, Juan; Garcia-Salum, Tamara; Rathnasinghe, Raveen; Barriga, Gonzalo; Tapia, Karla; Garcia, Victoria; Bucarey, Sergio; Jang, Yunho; Wentworth, David; Torremorell, Montserrat; Neira, Victor; Medina, Rafael A.
    Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population. Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains. These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.IMPORTANCEIn the global context, where swine serve as crucial intermediate hosts for influenza A viruses (IAVs), this study addresses the pressing concern of the zoonotic potential of novel reassortant strains. Conducted on a large scale in Chile, it presents a comprehensive account of swine influenza A virus diversity, covering 93.8% of the country's industrialized swine farms. The findings reveal eight distinct swine IAV genotypes, all carrying a complete internal gene cassette of pandemic H1N1 2009 origin, emphasizing potential increased replication and transmission fitness. Genetic divergence of H1N2 and H3N2 IAVs from globally reported strains raises alarms, with evidence suggesting introductions from human seasonal viruses since the mid-1980s. A detailed serological analysis underscores the zoonotic threat, indicating susceptibility in the general population to swine H3N2 and a lack of protective antibodies in vulnerable demographics. These data highlight the importance of continuous surveillance, providing crucial insights for global health organizations.
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    Reemergence of H3N8 Equine Influenza A virus in Chile, 2018
    (2018) Mena, Juan; Brito, Bárbara; Moreira, Rubén; Tadich, Tamara; González, Igor; Cruces, Jaime; Ortega, Rene; Bakel, Harm; Rathnasinghe, Raveen; Medina Silva, Rafael Andrés; Pizarro‐Lucero, José; Neira, Víctor
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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.