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Walther Mothes, PhD

Paul B. Beeson Professor of Medicine and Professor of Microbial Pathogenesis; Co-Leader, Cancer Microbiology

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.

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

Coauthors

Research Interests

Cell Biology; HIV; Immune System; Retroviridae

Selected Publications

  • SARS-Cov-2 variants of concern decelerate the dynamics of spike open conformation as an evolutionary strategyYang Z, Han Y, Ding S, Finzi A, Mothes W, Lu M. SARS-Cov-2 variants of concern decelerate the dynamics of spike open conformation as an evolutionary strategy Biophysical Journal 2022, 121: 39a. PMCID: PMC8833081, DOI: 10.1016/j.bpj.2021.11.2500.
  • Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus ParticlesLu M, Uchil P, Li W, Terry D, Gorman J, Zhang B, Zhou T, Ding S, Liu L, Ho D, Mascola J, Finzi A, Kwong P, Blanchard S, Mothes W. Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles Biophysical Journal 2021, 120: 276a. PMCID: PMC7879775, DOI: 10.1016/j.bpj.2020.11.1757.
  • A Biocontainment Procedure for Intravital Microscopy of High-Risk PathogensHaugh K, Pi R, Fontes B, Mothes W, Uchil P. A Biocontainment Procedure for Intravital Microscopy of High-Risk Pathogens Applied Biosafety 2018, 23: 211-222. DOI: 10.1177/1535676018785177.
  • P-C4 Associating HIV-1 Env trimer structures with functional Env conformational states by smFRET analysisLu M, Ma X, Castillo-Menendez L, Gorman J, Munro J, Kwong P, Blanchard S, Sodroski J, Mothes W. P-C4 Associating HIV-1 Env trimer structures with functional Env conformational states by smFRET analysis JAIDS Journal Of Acquired Immune Deficiency Syndromes 2018, 77: 58. DOI: 10.1097/01.qai.0000532510.14481.56.
  • Single-Molecule FRET Reveals an Additional Conformational State of HIV-1 Envelope Glycoprotein Critical for Vaccine DesignLu M, Ma X, R. C, Ermel U, S. T, Gorman J, Reichard N, Wang K, Grover J, Finzi A, Munro J, Kwong P, Blanchard S, Sodroski J, Mothes W. Single-Molecule FRET Reveals an Additional Conformational State of HIV-1 Envelope Glycoprotein Critical for Vaccine Design Biophysical Journal 2018, 114: 27a. DOI: 10.1016/j.bpj.2017.11.192.
  • Single-Molecule FRET Delineates Asymmetric Trimer Conformations during HIV-1 EntryMa X, Lu M, Terry D, Gorman J, Kwong P, Blanchard S, Munro J, Mothes W. Single-Molecule FRET Delineates Asymmetric Trimer Conformations during HIV-1 Entry Biophysical Journal 2017, 112: 177a. DOI: 10.1016/j.bpj.2016.11.980.
  • Proceedings of the Frontiers of Retrovirology Conference 2016Zurnic I, Hütter S, Lehmann U, Stanke N, Reh J, Kern T, Lindel F, Gerresheim G, Hamann M, Müllers E, Lesbats P, Cherepanov P, Serrao E, Engelman A, Lindemann D, Da Silva Santos C, Tartour K, Cimarelli A, Burdick R, Chen J, Sastri J, Hu W, Pathak V, Keppler O, Pradeau K, Eiler S, Levy N, Lennon S, Cianferani S, Emiliani S, Ruff M, Parissi V, Rato S, Rausell A, Munoz M, Telenti A, Ciuffi A, Zhyvoloup A, Melamed A, Anderson I, Planas D, Kriston-Vizi J, Ketteler R, Lee C, Merritt A, Ancuta P, Bangham C, Fassati A, Rodari A, Van Driessche B, Galais M, Delacourt N, Fauquenoy S, Vanhulle C, Kula A, Burny A, Rohr O, Van Lint C, van Montfort T, van der Sluis R, Speijer D, Berkhout B, Meng B, Rutkowski A, Berry N, Dölken L, Lever A, Schuster T, Asbach B, Wagner R, Gross C, Wiesmann V, Kalmer M, Wittenberg T, Gettemans J, Thoma-Kress A, Li M, Freed E, Liu S, Müller J, Münch J, Sewald X, Uchil P, Ladinsky M, Beloor J, Pi R, Herrmann C, Motamedi N, Murooka T, Brehm M, Greiner D, Mempel T, Bjorkman P, Kumar P, Mothes W, Joas S, Parrish E, Gnanadurai C, Lump E, Stürzel C, Parrish N, Sauermann U, Töpfer K, Schultheiss T, Bosinger S, Silvestri G, Apetrei C, Huot N, Müller-Trutwin M, Sauter D, Hahn B, Stahl-Hennig C, Kirchhoff F, Schumann G, Jung-Klawitter S, Fuchs N, Upton K, Muñoz-Lopez M, Shukla R, Wang J, Garcia-Canadas M, Lopez-Ruiz C, Gerhardt D, Sebe A, Grabundzija I, Gerdes P, Merkert S, Pulgarin A, Bock A, Held U, Witthuhn A, Haase A, Wolvetang E, Martin U, Ivics Z, Izsvák Z, Garcia-Perez J, Faulkner G, Hurst T, Katzourakis A, Magiorkinis G, Schott K, Derua R, Seifried J, Reuter A, Schmitz H, Tondera C, Brandariz-Nuñez A, Diaz-Griffero F, Janssens V, König R, Baldauf H, Stegmann L, Schwarz S, Trotard M, Martin M, Lenzi G, Burggraf M, Pan X, Fregoso O, Lim E, Abraham L, Erikson E, Nguyen L, Ambiel I, Rutsch F, Kim B, Emerman M, Fackler O, Wittmann S, Behrendt R, Volkmann B, Eissmann K, Gramberg T, Bolduan S, Koppensteiner H, Regensburg S, Brack-Werner R, Draenert R, Schindler M, Ducroux A, Xu S, Ponnurangam A, Franz S, Malassa A, Ewald E, Goffinet C, Fung S, Chan C, Yuen C, Kok K, Chan C, Jin D, Dittmer U, Kmiec D, Iyer S, Stürzel C, Hahn B, Ariumi Y, Yasuda-Inoue M, Kawano K, Tateishi S, Turelli P, Compton A, Roy N, Porrot F, Billet A, Casartelli N, Yount J, Liang C, Schwartz O, Magnus C, Reh L, Moore P, Uhr T, Weber J, Morris L, Trkola A, Grindberg R, Schlaepfer E, Schreiber G, Simon V, Speck R, Debyser Z, Vranckx L, Demeulemeester J, Saleh S, Verdin E, Cereseto A, Christ F, Gijsbers R, Wang G, Zhao N, Das A, Köstler J, Perdiguero B, Esteban M, Jacobs B, Montefiori D, LaBranche C, Yates N, Tomaras G, Ferrari G, Foulds K, Roederer M, Landucci G, Forthal D, Seaman M, Hawkins N, Self S, Phogat S, Tartaglia J, Barnett S, Burke B, Cristillo A, Ding S, Heeney J, Pantaleo G, Stab V, Ensser A, Tippler B, Burton D, Tenbusch M, Überla K, Alter G, Lofano G, Dugast A, Kulkarni V, Suscovich T, Opazo T, Barraza F, Herrera D, Garces A, Schwenke T, Tapia D, Cancino J, Arriagada G, Haußner C, Damm D, Rohrhofer A, Schmidt B, Eichler J, Midgley R, Wheeldon J, Piguet V, Khopkar P, Rohamare M, Kulkarni S, Godinho-Santos A, Hance A, Goncalves J, Mammano F, Gasser R, Hamoudi M, Pellicciotta M, Zhou Z, Visdeloup C, Colin P, Braibant M, Lagane B, Negroni M, Wamara J, Bannert N, Mesplede T, Osman N, Anstett K, Liang J, Pham H, Wainberg M, Shao W, Shan J, Kearney M, Wu X, Maldarelli F, Mellors J, Luke B, Coffin J, Hughes S, Fricke T, Opp S, Shepard C, Ivanov D, Valle-Casuso J, Kanja M, Cappy P, Negroni M, Lener D, Knyazhanskaya E, Anisenko A, Zatsepin T, Gottikh M, Komkov A, Minervina A, Nugmanov G, Nazarov V, Khodosevich K, Mamedov I, Lebedev Y, Colomer-Lluch M, Serra-Moreno R, Sarracino A, Gharu L, Pasternak A, Marcello A, McCartin A, Kulkarni A, Le Douce V, Gautier V, Baeyens A, Naessens E, Van Nuffel A, Weening K, Reilly A, Claeys E, Trypsteen W, Vandekerckhove L, Eyckerman S, Gevaert K, Verhasselt B, Mok H, Norton N, Fun A, Hirst J, Wills M, Miklik D, Senigl F, Hejnar J, Sakuragi J, Sakuragi S, Yokoyama M, Shioda T, Sato H, Bodem J, Moschall R, Denk S, Erkelenz S, Schenk C, Schaal H, Donhauser N, Socher E, Millen S, Sticht H, Gross C, Mann M, Wei G, Betts M, Liu Y, Kehl T, Russell R, Löchelt M, Hohn O, Mostafa S, Hanke K, Norley S, Chen C, Shingai M, Borrego P, Taveira N, Strebel K, Hellmund C, Meng B, Friedrich M, Hahn F, Setz C, Rauch P, Fraedrich K, Matthaei A, Henklein P, Traxdorf M, Fossen T, Schubert U, Khwaja A, Galilee M, Alian A, Schwalbe B, Hauser H, Schreiber M, Scherpenisse M, Cho Y, Kim J, Jeong D, Trejbalova K, Benesova M, Kucerova D, Vernerova Z, Amouroux R, Hajkova P, Elleder D, Hron T, Farkasova H, Padhi A, Paces J, Zhu H, Gifford R, Murcia P, Carrozza M, Niewiadomska A, Mazzei M, Abi-Said M, Hughes J, Hué S, Gifford R, Obasa A, Jacobs G, Engelbrecht S, Mack K, Starz K, Geyer M, Bibollet-Ruche F, Stürzel C, Leoz M, Plantier J, Argaw-Denboba A, Balestrieri E, Serafino A, Bucci I, Cipriani C, Spadafora C, Sinibaldi-Vallebona P, Matteucci C, Jayashree S, Neogi U, Chhangani A, Rathore S, Mathur B, Abati A, Koç B, Oğuzoğlu T, Shimauchi T, Caucheteux S, Turpin J, Finsterbusch K, Tokura Y, Souriant S, Balboa L, Pingris K, Kviatcowsky D, Raynaud-Messina B, Cougoule C, Mercier I, Kuroda M, González-Montaner P, Inwentarz S, Moraña E, del Carmen Sasiain M, Neyrolles O, Maridonneau-Parini I, Lugo-Villarino G, Vérollet C, Herrmann A, Thomas D, Bouzas N, Lahaye X, Bhargava A, Satoh T, Gentili M, Cerboni S, Silvin A, Conrad C, Ahmed-Belkacem H, Rodriguez E, Guichou J, Bosquet N, Piel M, Le Grand R, King M, Pawlotsky J, Manel N, Hofmann H, Vanwalscappel B, Bloch N, Landau N, Indik S, Hagen B, Valle-Casuso J, Allouch A, David A, Barré-Sinoussi F, Benkirane M, Pancino G, Saez-Cirion A, Lee W, Sloan R, Schulte B, Opp S, Blomberg J, Vargiu L, Rodriguez-Tomé P, Tramontano E, Sperber G, Kumari N, Ammosova T, Diaz S, Oneal P, Nekhai S, Fahrny A, Gers-Huber G, Audigé A, Jayaprakash A, Sachidanandam R, Hernandez M, Dillon-White M, Souriant S, Pingris K, Raynaud-Messina B, Cougoule C, Mercier I, Neyrolles O, Maridonneau-Parini I, Lugo-Villarino G, Maze E, Ham C, Almond N, Towers G, Belshaw R, de Sousa-Pereira P, Abrantes J, Pizzato M, Esteves P, Kahle T, Schmitt S, Merkel L, Reuter N, Stamminger T, Rosa I, Bishop K, Spinazzola A, Groom H, Vieyres G, Müsken M, Zillinger T, Hornung V, Barchet W, Häussler S, Pietschmann T, Javed A, Leuchte N, Salinas G, Opitz L, Sopper S, Mummert C, Hofmann C, Hückelhoven A, Bergmann S, Müller-Schmucker S, Harrer E, Dörrie J, Schaft N, Harrer T, Cardinaux L, Zahno M, Vogt H, Zanoni R, Bertoni G, Muenchhoff M, Goulder P, Keppler O, Rebensburg S, Helfer M, Zhang Y, Chen H, Bernier A, Gosselin A, Routy J, Wöhrl B, Schneider A, Corona A, Spöring I, Jordan M, Buchholz B, Maccioni E, Di Santo R, Schweimer K, Schölz C, Weinert B, Wagner S, Beli P, Miyake Y, Qi J, Jensen L, Streicher W, McCarthy A, Westwood N, Lain S, Cox J, Matthias P, Mann M, Bradner J, Choudhary C, Stern M, Valletta E, Frezza C, Marino-Merlo F, Grelli S, Serafino A, Mastino A, Macchi B, Kaulfuß M, Windmann S, Bayer W, Mikasi S, Jacobs G, Heß R, Bonsmann M, Kirschning C, Lepenies B, Kolenbrander A, Temchura V, Iijima K, Kobayashi J, Ishizaka Y. Proceedings of the Frontiers of Retrovirology Conference 2016 Retrovirology 2016, 13: 68. PMCID: PMC5046194, DOI: 10.1186/s12977-016-0294-5.
  • Conformational Dynamics of Single HIV-1 Envelope Proteins on the Surface of Native VirionsMunro J, Gorman J, Ma X, Zhou Z, Arthos J, Burton D, Koff W, Courter J, Smith A, Kwong P, Blanchard S, Mothes W. Conformational Dynamics of Single HIV-1 Envelope Proteins on the Surface of Native Virions Biophysical Journal 2015, 108: 362a-363a. DOI: 10.1016/j.bpj.2014.11.1988.
  • TRIM15 is a focal adhesion protein that regulates focal adhesion disassemblyUchil P, Pawliczek T, Pawliczek T, Reynolds T, Reynolds T, Ding S, Ding S, Hinz A, Hinz A, Munro J, Munro J, Huang F, Huang F, Floyd R, Floyd R, Yang H, Yang H, Hamilton W, Hamilton W, Bewersdorf J, Xiong Y, Xiong Y, Calderwood D, Mothes W. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly Development 2014, 141: e1906-e1906. DOI: 10.1242/dev.117242.
  • Cell-to-Cell Transmission of HIVAgosto L, Zhong P, Mothes W. Cell-to-Cell Transmission of HIV 2013, 167-184. DOI: 10.1007/978-1-4614-7729-7_7.
  • Conformational Dynamics of Single HIV Env Molecules on the Surface of Native VirionsMunro J, Zhu J, Stuckey J, Kwong P, Blanchard S, Mothes W. Conformational Dynamics of Single HIV Env Molecules on the Surface of Native Virions Biophysical Journal 2013, 104: 415a. DOI: 10.1016/j.bpj.2012.11.2311.
  • Ca2+ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomesCzibener C, Sherer N, Becker S, Pypaert M, Hui E, Chapman E, Mothes W, Andrews N. Ca2+ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomes Journal Of Experimental Medicine 2006, 203: i26-i26. DOI: 10.1084/jem20310oia26.
  • Time-Resolved Imaging of Single Retrovirus-Cell FusionMelikyan G, Barnard R, Abrahamyan L, Mothes W, Young J. Time-Resolved Imaging of Single Retrovirus-Cell Fusion Retrovirology 2005, 2: s4. DOI: 10.1186/1742-4690-2-s1-s4.
  • Cytomegalovirus uses multiple strategies to interfere with MHC class I-restricted antigen presentationWiertz E, Tortorella D, Bogyo M, Yu J, Galocha B, Mothes W, Jones T, Rapoport T, Ploegh H. Cytomegalovirus uses multiple strategies to interfere with MHC class I-restricted antigen presentation Immunology Letters 1997, 56: 189. DOI: 10.1016/s0165-2478(97)85759-8.