Walther H Mothes PhD

Associate Professor of Microbial Pathogenesis

Research Interests

cell biology; retroviral replication; retroviruses; immune; viral biology; genetic; biochemical; cell imaging; Viral entry and exit; Retroviruses including HIV

Research Summary

Dr. Mothes’ laboratory is interested in various aspects of viral spread and pathogenesis of HIV-1 and other retroviruses. Retroviruses can efficiently spread from cell to cell through contact zones, called virological and infectious synapses. The Mothes lab has contributed to this process by directly visualizing how cell-cell contracts between infected and uninfected cells form, virus assembly is directed towards cell-cell contact sites and viruses are actively transferred to infect neighboring cells. A major current interest of the laboratory is to monitor viral spread and aspects of retroviral pathogenesis directly in living animals using multi-photon laser scanning microscopy. The laboratory is also applying single molecule imaging to understand how conformational events in the HIV-1 envelope protein lead to fusion between viral and cellular membranes. A detailed understanding of these processes will permit the rational design of vaccines and antiviral therapies that prevent virus spreading and the infection of new cells.

Extensive Research Description

Our laboratory works on the cell biological aspects of retroviral replication. Retroviruses are small particles of about 100 nm that carry a viral RNA genome surrounded by a viral capsid and a membrane envelope. Given their simple composition, retroviruses depend on cellular processes throughout their replication cycle. In addition, viral replication evolved in the presence of a strong innate and adaptive immune defense. Thus, retroviral replication is the result of a complex interdependence of viral biology, the utilization of cellular biological machineries, and immune evasion. To understand the retroviral life cycle we apply an imaging approach complemented by cell biological, genetic, and biochemical techniques. Live cell imaging allows us to monitor how viral components come together during assembly, to understand how viruses are transmitted from cell to cell, to determine when and where retroviruses infect cells and finally, to analyze at which point antiviral factors interfere with these individual steps.

Selected Publications

  • Jin J., Li F., and Mothes W. (2011). Viral determinants of polarized assembly of the murine leukemia virus. J. Virol. 85(15):7672-82.
  • Mothes W, Sherer NM, Jin J, Zhong P. (2010). Virus cell-to-cell transmission. J Virol. 84(17):8360-8.
  • Jin J, Sherer NM, Heidecker G, Derse D and Mothes W. (2009) Assembly of the murine leukemia virus is directed towards sites of cell-cell contact PLoS Biol.7:e1000163
  • Sherer N.M., Lehmann N.M., Jimenez-Soto L.F., Horensavitz C., Pypert M., and Mothes W. (2007). Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission. Nature Cell Biol. 9(3), 310-315.

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