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Walther Mothes, PhD

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

Contact Information

Walther Mothes, PhD

Mailing Address

  • Microbial Pathogenesis

    Department of Microbial Pathogenesis, 295 Congress Avenue

    New Haven, CT 06519

    United States

Mothes Laboratory
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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

  • Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions.Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, Burton DR, Koff WC, Courter JR, Smith AB, Kwong PD, Blanchard SC, Mothes W. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science (New York, N.Y.) 2014, 346: 759-63. PMID: 25298114, PMCID: PMC4304640, DOI: 10.1126/science.1254426.
  • Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection.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. Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science (New York, N.Y.) 2015, 350: 563-567. PMID: 26429886, PMCID: PMC4651917, DOI: 10.1126/science.aab2749.
  • HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations.Ma X, Lu M, Gorman J, Terry DS, Hong X, Zhou Z, Zhao H, Altman RB, Arthos J, Blanchard SC, Kwong PD, Munro JB, Mothes W. HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. ELife 2018, 7 PMID: 29561264, PMCID: PMC5896952, DOI: 10.7554/eLife.34271.
  • A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus.Uchil PD, Pi R, Haugh KA, Ladinsky MS, Ventura JD, Barrett BS, Santiago ML, Bjorkman PJ, Kassiotis G, Sewald X, Mothes W. A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. Cell Host & Microbe 2019, 25: 87-100.e10. PMID: 30595553, PMCID: PMC6331384, DOI: 10.1016/j.chom.2018.11.011.
  • Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET.Lu M, Ma X, Castillo-Menendez LR, Gorman J, Alsahafi N, Ermel U, Terry DS, Chambers M, Peng D, Zhang B, Zhou T, Reichard N, Wang K, Grover JR, Carman BP, Gardner MR, Nikić-Spiegel I, Sugawara A, Arthos J, Lemke EA, Smith AB, Farzan M, Abrams C, Munro JB, McDermott AB, Finzi A, Kwong PD, Blanchard SC, Sodroski JG, Mothes W. Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Nature 2019, 568: 415-419. PMID: 30971821, PMCID: PMC6655592, DOI: 10.1038/s41586-019-1101-y.
  • In Vivo Imaging-Driven Approaches to Study Virus Dissemination and Pathogenesis.Uchil PD, Haugh KA, Pi R, Mothes W. In Vivo Imaging-Driven Approaches to Study Virus Dissemination and Pathogenesis. Annual Review Of Virology 2019, 6: 501-524. PMID: 31283440, PMCID: PMC7217087, DOI: 10.1146/annurev-virology-101416-041429.
  • Illuminating the virus life cycle with single-molecule FRET imaging.Lu M, Ma X, Mothes W. Illuminating the virus life cycle with single-molecule FRET imaging. Advances In Virus Research 2019, 105: 239-273. PMID: 31522706, PMCID: PMC7246055, DOI: 10.1016/bs.aivir.2019.07.004.
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