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3. Influenza-Mediated Lung Infection Models

Author

McGee, Charles E., primary, Sample, Christopher J., additional, Kilburg-Basnyat, Brita, additional, Gabor, Kristin A., additional, Fessler, Michael B., additional, and Gowdy, Kymberly M., additional

Published
2019
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5. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination

Author

Pardi, Norbert, Hogan, Michael J., Pelc, Rebecca S., Muramatsu, Hiromi, Andersen, Hanne, DeMaso, Christina R., Dowd, Kimberly A., Sutherland, Laura L., Scearce, Richard M., Parks, Robert, Wagner, Wendeline, Granados, Alex, Greenhouse, Jack, Walker, Michelle, Willis, Elinor, Yu, Jae-Sung, McGee, Charles E., Sempowski, Gregory D., Mui, Barbara L., Tam, Ying K., Huang, Yan-Jang, Vanlandingham, Dana, Holmes, Veronica M., Balachandran, Harikrishnan, Sahu, Sujata, Lifton, Michelle, Higgs, Stephen, Hensley, Scott E., Madden, Thomas D., Hope, Michael J., Karikó, Katalin, Santra, Sampa, Graham, Barney S., Lewis, Mark G., Pierson, Theodore C., Haynes, Barton F., and Weissman, Drew

Published
2017
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9. Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation

Author

Yamane, Daisuke, McGivern, David R., Wauthier, Eliane, Yi, MinKyung, Madden, Victoria J., Welsch, Christoph, Antes, Iris, Wen, Yahong, Chugh, Pauline E., McGee, Charles E., Widman, Douglas G., Misumi, Ichiro, Bandyopadhyay, Sibali, Kim, Seungtaek, Shimakami, Tetsuro, Oikawa, Tsunekazu, Whitmire, Jason K., Heise, Mark T., Dittmer, Dirk P., Kao, C.Cheng, Pitson, Stuart M., Merrill, Jr., Alfred H., Reid, Lola M., and Lemon, Stanley M.

Subjects
Lipid peroxidation -- Health aspects -- Physiological aspects, Sphingosine -- Health aspects -- Physiological aspects, Hepatitis C virus -- Health aspects -- Distribution, Company distribution practices, Biological sciences, Health
Abstract

Oxidative tissue injury often accompanies viral infection, yet there is little understanding of how it influences virus replication. We show that multiple hepatitis C virus (HCV) genotypes are exquisitely sensitive to oxidative membrane damage, a property distinguishing them from other pathogenic RNA viruses. Lipid peroxidation, regulated in part through sphingosine kinase-2, severely restricts HCV replication in Huh-7 cells and primary human hepatoblasts. Endogenous oxidative membrane damage lowers the 50% effective concentration of direct-acting antivirals in vitro, suggesting critical regulation of the conformation of the NS3-4A protease and the NS5B polymerase, membrane-bound HCV replicase components. Resistance to lipid peroxidation maps genetically to transmembrane and membrane-proximal residues within these proteins and is essential for robust replication in cell culture, as exemplified by the atypical JFH1 strain of HCV. Thus, the typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation, providing a mechanism for attenuating replication in stressed tissue and possibly facilitating long-term viral persistence., Reactive oxygen species (ROS) are an unavoidable byproduct of aerobic metabolism and a double-edged sword for complex cellular systems (1). Although central to many disease states, ROS also function as [...]

Published
2014
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11. Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism

Author

Watanabe, Akiko, primary, McCarthy, Kevin R., additional, Kuraoka, Masayuki, additional, Schmidt, Aaron G., additional, Adachi, Yu, additional, Onodera, Taishi, additional, Tonouchi, Keisuke, additional, Caradonna, Timothy M., additional, Bajic, Goran, additional, Song, Shengli, additional, McGee, Charles E., additional, Sempowski, Gregory D., additional, Feng, Feng, additional, Urick, Patricia, additional, Kepler, Thomas B., additional, Takahashi, Yoshimasa, additional, Harrison, Stephen C., additional, and Kelsoe, Garnett, additional

Published
2019
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12. Chikungunya virus adaptation to Aedes albopictus mosquitoes does not correlate with acquisition of cholesterol dependence or decreased pH threshold for fusion reaction

Author

McGee Charles E, Tsetsarkin Konstantin A, and Higgs Stephen

Subjects
Chikungunya virus, Aedes albopictus, cholesterol, pH threshold of fusion, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that recently caused several large scale outbreaks/epidemics of arthritic disease in tropics of Africa, Indian Ocean basin and South-East Asia. This re-emergence event was facilitated by genetic adaptation (E1-A226V substitution) of CHIKV to a newly significant mosquito vector for this virus; Aedes albopictus. However, the molecular mechanism explaining the positive effect of the E1-A226V mutation on CHIKV fitness in this vector remains largely unknown. Previously we demonstrated that the E1-A226V substitution is also associated with attenuated CHIKV growth in cells depleted by cholesterol. Methods In this study, using a panel of CHIKV clones that varies in sensitivity to cholesterol, we investigated the possible relationship between cholesterol dependence and Ae. albopictus infectivity. Results We demonstrated that there is no clear mechanistic correlation between these two phenotypes. We also showed that the E1-A226V mutation increases the pH dependence of the CHIKV fusion reaction; however, subsequent genetic analysis failed to support an association between CHIKV dependency on lower pH, and mosquito infectivity phenotypes. Conclusion the E1-A226V mutation probably acts at different steps of the CHIKV life cycle, affecting multiple functions of the virus.

Published
2011
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13. A robust microparticle platform for a STING-targeted adjuvant that enhances both humoral and cellular immunity during vaccination

Author

Junkins, Robert D., primary, Johnson, Brandon M., additional, Gallovic, Matthew D., additional, Collier, Michael A., additional, Watkins-Schulz, Rebekah, additional, Cheng, Ning, additional, David, Clement N, additional, McGee, Charles E., additional, Sempowski, Gregory D, additional, Shterev, Ivo, additional, McKinnon, Karen, additional, Bachelder, Eric M., additional, Ainslie, Kristy M., additional, and Ting, Jenny P-Y, additional

Published
2017
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14. Gamma-delta T cells play a protective role in chikungunya virus-induced disease

Author

Heise, Mark T., Lim, Jean K., Whitmore, Alan C., McGee, Charles E., Ferris, Martin T., Long, Kristin M., Thurlow, Lance R., Montgomery, Stephanie A., and Rodriguez, Carlos A.

Subjects
virus diseases
Abstract

Chikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. As CHIKV is initially introduced into the skin where γδ T cells are prevalent, we evaluated their response to CHIKV infection. CHIKV infection led to a significant increase in γδ T cells in the infected foot and draining lymph node associated with the production of pro-inflammatory cytokines and chemokines in C57BL/6J mice. γδ T cell-/- mice demonstrated exacerbated CHIKV disease characterized by less weight gain and greater foot swelling compared to wild-type mice as well as a transient increase in monocytes and altered cytokine/chemokine expression in the foot. Histologically, γδ T cell-/- mice had increased inflammation-mediated oxidative damage in the ipsilateral foot and ankle joint of versus wild-type mice which was independent of differences in CHIKV replication. These results suggest that γδ T cells play a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage. Recent epidemics including the 2004-2007 outbreak and the spread of CHIKV to naïve populations in the Caribbean, Central and South America with resultant cases imported into the U.S highlighted the capacity of CHIKV to cause explosive epidemics where the virus can spread to millions of people and rapidly move into new areas. These studies identify γδ T cells as being important to both recruitment of key inflammatory cell populations and dampening the tissue injury due to oxidative stress. Given the importance of these cells in the early response to CHIKV, this information may inform the development of CHIKV vaccines and therapeutics.

Published
2015
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18. In Vivo Imaging of Chikungunya Virus in Mice and Aedes Mosquitoes Using a Renilla Luciferase Clone

Author

Nuckols, John, Huang, Yan-Jang Scott, McGee, Charles E., Ziegler, Sarah A., Higgs, Stephen, Vanlandingham, Dana L., and Tesh, Robert B.

Subjects
viruses, fungi, virus diseases
Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that in humans causes an acute febrile illness characterized by fever, arthralgia, and rash. It is currently associated with large outbreaks in Asia, Africa, and islands of the Indian Ocean and has been introduced from these tropical regions into Europe, where local transmission has been recorded on two occasions. The underlying basis of the pathogenesis of CHIKV and related alphaviruses that produce similar symptoms remains unclear. By applying new techniques, for example, in vivo imaging in live animals and arthropods, we may improve our understanding of viral pathogenesis in vertebrates and viral replication in mosquitoes. This technical report describes the evaluation of a CHIKV–luciferase clone to visualize infection and dissemination in both Aedes aegypti and Aedes albopictus mosquitoes and mice. In mosquitoes, luciferase activity was seen at 3 and 7 days post-infection in both head and abdomens. In vivo imaging of CHIKV–luciferase was detected in mice for up to 5 days post-infection at the site of inoculation with limited dissemination to the skeletal muscle.

Published
2011
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19. Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus

Author

Smith, Scott A., primary, Silva, Laurie A., additional, Fox, Julie M., additional, Flyak, Andrew I., additional, Kose, Nurgun, additional, Sapparapu, Gopal, additional, Khomandiak, Solomiia, additional, Ashbrook, Alison W., additional, Kahle, Kristen M., additional, Fong, Rachel H., additional, Swayne, Sherri, additional, Doranz, Benjamin J., additional, McGee, Charles E., additional, Heise, Mark T., additional, Pal, Pankaj, additional, Brien, James D., additional, Austin, S. Kyle, additional, Diamond, Michael S., additional, Dermody, Terence S., additional, and Crowe, James E., additional

Published
2015
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20. Mutational analysis of the West Nile virus NS4B protein

Author

Wicker, Jason A., primary, Whiteman, Melissa C., additional, Beasley, David W.C., additional, Davis, C. Todd, additional, McGee, Charles E., additional, Lee, J. Ching, additional, Higgs, Stephen, additional, Kinney, Richard M., additional, Huang, Claire Y.-H., additional, and Barrett, Alan D.T., additional

Published
2012
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22. Vector Competence of Australian Mosquitoes for Yellow Fever Virus

Author

van den Hurk, Andrew F., primary, Higgs, Stephen, additional, McGee, Charles E., additional, Hall-Mendelin, Sonja, additional, Day, Andrew, additional, Ryan, Peter A., additional, McElroy, Kate, additional, Ritchie, Scott A., additional, Pyke, Alyssa T., additional, and Vanlandingham, Dana L., additional

Published
2011
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26. Transcriptome Changes in Culex quinquefasciatus (Diptera: Culicidae) Salivary Glands During West Nile Virus Infection

Author

Girard, Yvette A., primary, Mayhew, George F., additional, Fuchs, Jeremy F., additional, Li, Huarong, additional, Schneider, Bradley S., additional, McGee, Charles E., additional, Rocheleau, Thomas A., additional, Helmy, Hanan, additional, Christensen, Bruce M., additional, Higgs, Stephen, additional, and Bartholomay, Lyric C., additional

Published
2010
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27. Transcriptome Changes inCulex quinquefasciatus(Diptera: Culicidae) Salivary Glands During West Nile Virus Infection

Author

Girard, Yvette A., primary, Mayhew, George F., additional, Fuchs, Jeremy F., additional, Li, Huarong, additional, Schneider, Bradley S., additional, McGee, Charles E., additional, Rocheleau, Thomas A., additional, Helmy, Hanan, additional, Christensen, Bruce M., additional, Higgs, Stephen, additional, and Bartholomay, Lyric C., additional

Published
2010
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42. Color blind at the front lines

Author

McGee, Charles E.

Subjects
Iraq-Kuwait Crisis, 1990-1991 -- Social aspects, African American soldiers -- Beliefs, opinions and attitudes
Published
1990

43. READERS REPORT.

Author

McGee, Charles E., Morrison, Robert S., and Wallace, H. O.

Subjects
LETTERS to the editor, EMPLOYEE theft, INHERITANCE & transfer tax, HOME prices
Abstract

Several letters to the editor are presented in response to articles in previous issues related to business in the U.S. including the coverage on the revelation of waterfront pilferage in the February 23, 1963 issue, the reference to gift and estate tax planning in the February 23, 1963 issue, the cost of housing in Honolulu, Hawaii in the March 2, 1963 issue.

Published
1963

44. Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation

Author

McGee, Charles E, Lemon, Stanley M, Madden, Victoria J, Kao, C Cheng, Wen, Yahong, Pitson, Stuart M, Widman, Douglas G, Dittmer, Dirk P, Misumi, Ichiro, Oikawa, Tsunekazu, Antes, Iris, Shimakami, Tetsuro, Whitmire, Jason K, Bandyopadhyay, Sibali, Chugh, Pauline E, Reid, Lola M, Merrill, Alfred H, Heise, Mark T, Welsch, Christoph, and Kim, Seungtaek

Subjects
viruses, 3. Good health
Abstract

Although oxidative tissue injury often accompanies viral infection, there is little understanding of how it influences virus replication. We show that multiple hepatitis C virus (HCV) genotypes are exquisitely sensitive to oxidative membrane damage, a property distinguishing them from other pathogenic RNA viruses. Lipid peroxidation, regulated in part through sphingosine kinase 2, severely restricts HCV replication in Huh-7 cells and primary human hepatoblasts. Endogenous oxidative membrane damage lowers the 50% effective concentration of direct-acting antivirals, suggesting critical regulation of the conformation of the NS3/4A protease and NS5B polymerase, membrane-bound HCV replicase components. Resistance to lipid peroxidation maps genetically to trans-membrane and membrane-proximal residues within these proteins, and is essential for robust replication in cell culture, as exemplified by the atypical JFH1 strain. Thus, the typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation, providing a novel mechanism for attenuating replication in stressed tissue and possibly facilitating long-term viral persistence.

45. Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus

Author

Silva, Laurie A., Kose, Nurgun, Pal, Pankaj, Diamond, Michael S., Doranz, Benjamin J., McGee, Charles E., Kahle, Kristen M., Sapparapu, Gopal, Swayne, Sherri, Brien, James D., Dermody, Terence S., Ashbrook, Alison W., Fong, Rachel H., Flyak, Andrew I., Smith, Scott A., Heise, Mark T., Fox, Julie M., Khomandiak, Solomiia, Crowe, James E., and Austin, S. Kyle

Subjects
virus diseases, 3. Good health
Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/mL), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.

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