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Kathryn Holmes, Professor

Ph.D. (1968), Rockefeller University
 

 

 

Contact Info:

Molecular Biology
University of Colorado

Kathryn Holmes, Ph.D.  Research One North
(RC1-North), Room 9117 Kathryn.Holmes@ucdenver.edu Phone: 303-724-4231

Enveloped viruses infect cells that express specific virus receptors by fusion of the viral envelope with host cell membranes. Membrane fusion is mediated by spike glycoproteins on the viral envelope. Coronavirus entry is mediated by a single large spike glycoprotein, S, that undergoes conformational changes when bound to its specific cellular receptor at 37°C. Our lab has characterized the spike glycoproteins of murine coronavirus MHV and human coronavirus HCoV-229E. We have identified receptors for MHV (murine CEACAM1a), HCoV-229E (human aminopeptidase N), and feline coronaviruses (feline aminopeptidase N). We are exploring the structure and functions of the S glycoproteins and their interactions with their receptors to elucidate the molecular mechanisms of coronavirus entry.

We are studying animal models that have genetically manipulated coronavirus receptors to examine the role of virus receptors in viral pathogenesis.

We are studying the structure and functions S protein of the SARS-coronavirus (SARS-CoV). In particular we are interested in identifying the receptor for the SARS-CoV and identifying conformational changes associated with virus infection. These studies will reveal new targets for anti-viral drugs and may show how the SARS-CoV entered the human population from an animal reservoir.​​​​​​​

 

Zelus, B.D., Wessner, D.R., Williams, R.K., Pensiero, M. N., Phibbs ,F.T., deSouza, M., Dveksler, G.S., and Holmes, K.V. Purifed, soluble MHVR, Bgp1b and Bgp2 murine coronavirus receptors differ in mouse hepatitis virus binding and neutralizing activities. J. Virol. 72:7237-7244 (1998).

Wang, G., Deering, C., Macke, M., Shao, J., Burns, R., Blau, D.M., Holmes, K.V., Davidson, B.L., Perlman, S., and McCray, P.B., Jr. Human coronavirus 229E infects polarized airway epithelia from the apical surface. J. Virol. 74:9234-9239 (2000)

Wentworth, D.E. and Holmes, K.V. Molecular determinants of species specificity in the coronavirus receptor aminopeptidase N (CD13): Influence of N-linked glycosylation J Virol.75:9741-52 (2001)

Blau DM, Turbide C, Tremblay M, Olson M, Letourneau S, Michaliszyn E, Jothy S, Holmes KV, Beauchemin N Targeted disruption of the Ceacam1 (MHVR) gene leads to reduced susceptibility of mice to MHV infection. J. Virol. Sep;75(17):8173-86. (2001)

Nakajima A, Iijima H, Neurath MF, Nagaishi T, Nieuwenhuis EE, Raychowdhury R, Glickman J, Blau DM, Russell S, Holmes KV, Blumberg RS. Activation-induced expression of carcinoembryonic antigen-cell adhesion molecule 1 regulates mouse T lymphocyte function. J Immunol. Feb 1;168(3):1028-35. (2002)

Tan*, K, Zelus,* B.D., Meijers*, R., Liu, J.H., Bergelson, J.M., Duke, N., Zhang,,R., Joachimiak, A., Holmes, K.V., and Wang, J.H. Crystal structure of murine sCEACAM1a[1,4]: A coronavirus receptor in the CEA family EMBO J. 21:2076-2086 (2002)(* indicates co-first authors)

Zelus, B.D., Schickli, J.H., Blau, D.M., Weiss, S.R. and Holmes, K.V. Conformational changes in the spike glycoprotein of murine coronavirus are induced at 37oC either by soluble murine CEACAM1 receptors or by pH 8. J. Virol. 77:830-840 (2003)

Tsai, J.C., Zelus, B.D., Holmes, K.V., and Weiss, S.R. The N-terminal domain of the murine coronavirus spike glycoprotein determines the CEACAM1 receptor specificity of the virus strain. J. Virol.77:841-850 (2003)

Bonavia, A, Zelus, B.D., Wentworth, D.E., Talbot, P.J., and Holmes, K.V. Identification of a receptor binding domain of the spike glycoprotein of human coronavirus HCoV-229E. J. Virol. 77:2530-8 (2003)

Breslin, J.J., Mork, I., Smith, M.K., Vogel, L.K., Hemmila, E.M., Bonavia, A., Talbot, P.J., Sjostrom, H., Noren, O., and Holmes, K.V. Human coronavirus 229E: Receptor binding domain and neutralization by soluble receptor at 37oC. J. Virol., 77:4435-4438 (2003)

Holmes, K.V., Editorial perspective: SARS-Associated Coronavirus, N. Eng. J. Med. 348:1948-1951 (2003)

Holmes, K.V., Spotlight article: SARS Coronavirus: A new challenge for prevention and therapy, J. Clin. Invest. 111:1605-1609 (2003)

Holmes, K.V. and Enjuanes, L. Perspective. The SARS Coronavirus: A postgenomic era. Science 300:1377-1378 (2003).