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Full-Text Articles in Life Sciences

Caspase 3-Dependent Cell Death Of Neurons Contributes To The Pathogenesis Of West Nile Virus Encephalitis, M. A. Samuel, John D. Morrey, M. S. Diamond Jan 2007

Caspase 3-Dependent Cell Death Of Neurons Contributes To The Pathogenesis Of West Nile Virus Encephalitis, M. A. Samuel, John D. Morrey, M. S. Diamond

John D. Morrey

West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that has become a significant global cause of viral encephalitis. To examine the mechanisms of WNV-induced neuronal death and the importance of apoptosis in pathogenesis, we evaluated the role of a key apoptotic regulator, caspase 3. WNV infection induced caspase 3 activation and apoptosis in the brains of wild-type mice. Notably, congenic caspase 3–/– mice were more resistant to lethal WNV infection, although there were no significant differences in the tissue viral burdens or the kinetics of viral spread. Instead, decreased neuronal death was observed in the cerebral cortices, brain stems, …


Defining Limits Of Treatment With Humanized Neutralizing Monoclonal Antibody For West Nile Virus Neurological Infection In A Hamster Model, John D. Morrey, V. Siddharthan, Aaron L. Olsen, H. Wang, Justin G. Julander, Jeffery O. Hall, H. Li, J. L. Nordstrom, S. Koenig, S. Johnson, M. S. Diamond Jan 2007

Defining Limits Of Treatment With Humanized Neutralizing Monoclonal Antibody For West Nile Virus Neurological Infection In A Hamster Model, John D. Morrey, V. Siddharthan, Aaron L. Olsen, H. Wang, Justin G. Julander, Jeffery O. Hall, H. Li, J. L. Nordstrom, S. Koenig, S. Johnson, M. S. Diamond

John D. Morrey

A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal antibody, hE16, was previously shown to improve the survival of WNV-infected hamsters when it was administered intraperitoneally (i.p.), even after the virus had infected neurons in the brain. In this study, we evaluated the therapeutic limit of hE16 for the treatment of WNV infection in hamsters by comparing single-dose peripheral (i.p.) therapy with direct administration into the pons through a convection-enhanced delivery (CED) system. At day 5 after infection, treatments with hE16 by the peripheral and the CED routes were equally effective at reducing morbidity and mortality. In contrast, at day 6 …


Efficacy Of Orally Administered T-705 On Lethal Avian Influenza A (H5n1) Virus Infections In Mice, R. W. Sidwell, Dale L. Barnard, C. W. Day, Donald F. Smee, K. W. Bailey, M. H. Wong, John D. Morrey, Y. Furuta Jan 2007

Efficacy Of Orally Administered T-705 On Lethal Avian Influenza A (H5n1) Virus Infections In Mice, R. W. Sidwell, Dale L. Barnard, C. W. Day, Donald F. Smee, K. W. Bailey, M. H. Wong, John D. Morrey, Y. Furuta

John D. Morrey

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) was inhibitory to four strains of avian H5N1 influenza virus in MDCK cells, with the 90% effective concentrations ranging from 1.3 to 7.7 µM, as determined by a virus yield reduction assay. The efficacy was less than that exerted by oseltamivir carboxylate or zanamivir but was greater than that exerted by ribavirin. Experiments with mice lethally infected with influenza A/Duck/MN/1525/81 (H5N1) virus showed that T-705 administered per os once, twice, or four times daily for 5 days beginning 1 h after virus exposure was highly inhibitory to the infection. Dosages from 30 to 300 mg/kg of body weight/day …


Neutralizing Viruses In Suspensions By Copper Oxide-Based Filters, G. Borkow, R. W. Sidwell, Donald F. Smee, Dale L. Barnard, John D. Morrey, H. H. Lara-Villegas, Y. Shemer-Avni, J. Gabbay Jan 2007

Neutralizing Viruses In Suspensions By Copper Oxide-Based Filters, G. Borkow, R. W. Sidwell, Donald F. Smee, Dale L. Barnard, John D. Morrey, H. H. Lara-Villegas, Y. Shemer-Avni, J. Gabbay

John D. Morrey

We report the capacity of copper oxide-containing filters to reduce infectious titers of a panel of viruses spiked into culture media. Enveloped, nonenveloped, RNA, and DNA viruses were affected, suggesting the possibility of using copper oxide-containing devices to deactivate a wide spectrum of infectious viruses found in filterable suspensions.