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Staff photo Gisa Gerold

Gisa Gerold

Virus entry into cells: host protein networks guiding virus infection and how we can block them

Contact

Works at

Affiliation
Associate professor at Department of Clinical Microbiology
Location
Universitetssjukhuset by 6 o 24 Umeå universitet, 901 85 Umeå
Affiliation
Location
Umeå universitet, 901 87 Umeå

Viruses need to enter host cells to replicate, spread and cause disease. During this entry process, viruses hijack cellular protein interaction networks. Viruses bind to attachment factors and receptors on the cell surface and use entry cofactors to trigger a coordinated and productive uptake into cells.

It is of clinical relevance to understand the molecular details of virus entry, since these host entry factors can be targeted with drugs. In particular protein interactions specifically induced and/or used by viruses are attractive drug targets. Importantly, such host targeting agents have the big advantage of being refractory to the development of drug resistance mutations.

Studying virus entry is furthermore significant, as host entry factors can determine, which tissues in the human body and/or which species a specific virus can infect. It can thus help understand the diseases caused by viruses and the potential risk of zoonotic infections, i.e. the spread of viruses from animals to humans.

Our research aims at elucidating the protein networks operating during the entry of mosquito-transmitted viruses of the Flaviviridae and Togaviridae families including Chikungunya virus and Zika virus. Viruses of these two families can cause pathologies ranging from arthritis to encephalitis and microcephaly. While some of the viruses under investigation are well adapted to the human host, others are not. Our goal is to identify host factors for virus entry and to investigate if these host factors are causative for tissue and species tropism.

The methods we apply are state of the art quantitative proteomics in conjunction with RNA interference, CRISPR/Cas9 knockout techniques, pharmacological perturbation and in vitro infection assays. We have developed affinity enrichment mass spectrometry methods, which allow us to monitor snapshots of protein networks engaged during virus entry. This is the basis of our follow up work using tissue culture infection assays with virus isolates and reporter strains as well as in vivo work in mice and mosquitoes.

Our work is highly collaborative with tight connections to world-leading national and international experts in arbovirus biology, mouse and mosquito work, as well as high resolution mass spectrometry. The current projects are funded by the Knut and Alice Wallenberg foundation and Umeå university. Please also visit the website of our second branch in Germany (www.twincore.de/en/gerold), with which we work closely together, and our joint Twitter account (https://twitter.com/GeroldLab).

Advances in Virus Research, Elsevier 2021 : 63-104
Zapatero-Belinchón, Francisco José; Carriquí-Madroñal, Belén; Gerold, Gisa
Medical Microbiology and Immmunology, Springer 2020, Vol. 209, (4) : 499-514
Alberione, Maria Pia; Moeller, Rebecca; Kirui, Jared; et al.
Science Advances, American Association for the Advancement of Science 2020, Vol. 6, (45)
Brown, Richard J. P.; Tegtmeyer, Birthe; Sheldon, Julie; et al.
Cold Spring Harbor Perspectives in Medicine, Cold Spring Harbor Laboratory Press (CSHL) 2020, Vol. 10, (2)
Gerold, Gisa; Moeller, Rebecca; Pietschmann, Thomas
PLoS Neglected Tropical Diseases, Public Library of Science 2020, Vol. 14, (12)
Moreno, Hector; Rastrojo, Alberto; Pryce, Rhys; et al.
Journal of Biological Chemistry
Palor, Machaela; Stejskal, Lenka; Mandal, Piya; et al.
mBio, American Society for Microbiology 2019, Vol. 10, (2)
Herrador, Antonio; Fedeli, Chiara; Radulovic, Emilia; et al.
Journal of Virology, Washington: American Society of Microbiology 2019, Vol. 93, (19)
Moreno, Hector; Moeller, Rebecca; Fedeli, Chiara; et al.
Molecular & Cellular Proteomics, American Society for Biochemistry and Molecular Biology 2019, Vol. 18, (12) : 2401-2417
Uckeley, Zina M.; Moeller, Rebecca; Kuhn, Lars I.; et al.
Viruses, MDPI 2019, Vol. 11, (3)
Zapatero-Belinchon, Francisco J.; Dietzel, Erik; Dolnik, Olga; et al.
Viruses, Vol. 10, (4)
Banse, Pia; Moeller, Rebecca; Bruening, Janina; et al.
PLoS Pathogens, Vol. 14, (7)
Bruening, Janina; Lasswitz, Lisa; Banse, Pia; et al.
Journal of Virology, Vol. 92, (5)
Fedeli, Chiara; Torriani, Giulia; Galan-Navarro, Clara; et al.
Journal of Molecular Biology, Vol. 430, (13) : 1863-1882
Lasswitz, Lisa; Chandra, Naresh; Arnberg, Niklas; et al.
Journal of Immunology Research
Bruening, Janina; Weigel, Bettina; Gerold, Gisa
Molecular & Cellular Proteomics, American Society for Biochemistry and Molecular Biology 2017, Vol. 16, (4) : 75-91
Gerold, Gisa; Bruening, Janina; Weigel, Bettina; et al.
Virus Research, Elsevier 2016, Vol. 218 : 25-39
Gerold, Gisa; Bruening, Janina; Pietschmann, Thomas
PLoS Pathogens, Public Library Science 2016, Vol. 12, (4)
Vieyres, Gabrielle; Welsch, Kathrin; Gerold, Gisa; et al.
mBio, American Society for Microbiology 2016, Vol. 7, (6)
von Schaewen, Markus; Dorner, Marcus; Hueging, Kathrin; et al.
Cell reports, Vol. 12, (5) : 864-878
Gerold, Gisa; Meissner, Felix; Bruening, Janina; et al.
eLIFE, Vol. 4
Lump, Edina; Castellano, Laura M; Meier, Christoph; et al.
Hepatology, Vol. 62, (1) : 57-67
Scull, Margaret A; Shi, Chao; de Jong, Ype P; et al.
Hepatology, Wiley-Blackwell 2014, Vol. 59, (2) : 363-5
Gerold, Gisa; Pietschmann, Thomas
Digestive Diseases, S. Karger 2014, Vol. 32, (5) : 525-537
Gerold, Gisa; Pietschmann, Thomas
Hepatology, Hoboken: Wiley-Blackwell 2013, Vol. 57, (3) : 1275-1277
Gerold, Gisa; Pietschmann, Thomas
Virology, San Diego: Academic Press 2013, Vol. 444, (1-2) : 1-11
Vogt, Alexander; Scull, Margaret A; Friling, Tamar; et al.
Nature Medicine, Vol. 17, (5) : 542-4
Gerold, Gisa; Rice, Charles M
Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences 2011, Vol. 108, (28) : 11608-11613
Kapoor, Amit; Simmonds, Peter; Gerold, Gisa; et al.
Hepatology, American Association for the Study of Liver Diseases 2010, Vol. 52, (6) : 2233-2236
Gerold, Gisa; Rice, Charles M; Ploss, Alexander
Nature Immunology, Vol. 9, (7) : 761-8
Gerold, Gisa; Abu Ajaj, Khalid; Bienert, Michael; et al.
Ernst Schering Foundation symposium proceedings, (3) : 83-95
de Diego, J L; Gerold, Gisa; Zychlinsky, A
Seminars in Immunology, Vol. 19, (1) : 41-7
Gerold, Gisa; Zychlinsky, Arturo; de Diego, Juana L
Biochemistry, Vol. 44, (12) : 4691-8
Loll, Bernhard; Gerold, Gisa; Slowik, Daria; et al.

Research groups

Head of research
Gisa Gerold