Cell Biology; HIV; Immune System; Retroviridae; Biochemical Processes
Microbial Pathogenesis: Mothes Lab
Molecular Virology: Virology laboratories
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.
Specialized Terms: cell biology; retroviral replication; retroviruses; immune; viral biology; genetic; biochemical; cell imaging; Viral entry and exit; Retroviruses including HIV
- Sewald X, Ladinsky MS, Uchil PD, Beloor J, Pi R, Herrmann C, Motamedi N, Murooka TT, Brehm MA, Greiner DL, Shultz LD, Mempel TR, Bjorkman PJ, Kumar P, Mothes W. (2015). Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science 350(6260):563-7.4.
- Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, Burton DR, Koff WC, Courter JR, Smith III AB, Kwong PD, Blanchard SC & Mothes W. (2014). Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science 346(6210):759-63.
- Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, Huang J, Acharya P, Chuang GY, Ofek G, Stewart-Jones GB, Stuckey J, Bailer RT, Joyce MG, Louder MK, Tumba N, Yang Y, Zhang B, Cohen MS, Haynes BF, Mascola JR, Morris L, Munro JB, Blanchard SC, Mothes W, Connors M, and Kwong PD. (2014). Structure and immune recognition of trimeric prefusion HIV-1 Env. Nature 514(7523):455-61
- Agosto LM, Zhong P, Munro J and Mothes W: Highly active antiretroviral therapies are effective against HIV-1 cell-to-cell transmission. (2014). PLoS Pathog. 2014 Feb;10 (2) :e1003982. Epub 2014 Feb 27.
- 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.