Arthropod-borne viruses are better known by their acronym, arboviruses. This term refers to an exceptionally diverse group of viruses transmitted to humans and other vertebrates by multiple arthropod vectors such as fleas, flies, midges, mosquitoes, and ticks. Even with the diversity of vectors, these viruses share the characteristics of having a complex dual life cycle, involving replication in both vertebrate hosts and arthropod vectors (Figure 1). Arboviruses virtually exist in any known habitat, and thus far, over 500 isolates have been identified within five distinct viral families (Reo-, Rhabdo-, Toga-, Flavi-, and Bunyaviridae). Many arboviruses are important pathogens in livestock and humans, causing severe health problems, often fatal, such as hepatitis, encephalitis, and hemorrhagic fever. Outbreaks are no longer limited to tropical and developing countries. With international trade, travel, and climate change that favors the spread of vectors to new areas, arboviruses are emerging and re-emerging agents of disease that represent a global threat for agricultural productivity and public health. A recent illustration is the rapid spread of the mosquito-borne virus Zika, from Africa to Pacific and to both South and North America. As such, many arboviruses are listed as high-priority pathogens by the World Health Organization and the need to develop research, diagnostic, and therapeutic tools to combat epidemic and pandemic arboviral infections is urgent.

The overall aim of the iWays team is to obtain a deep knowledge of the biology of viruses transmitted by mosquitoes and ticks, both in their arthropod vectors and in the human host. Our goal is to fully understand the arthropod vector-to-human host transmission with the ultimate objective of identifying novel antiviral strategies. To this end, we employ cellular and molecular techniques in combination with quantitative OMICS technologies, electron microscopy, and high-end fluorescence-based methods to (1) characterize arboviruses in both arthropod vector cells and mammalian host cells and (2) investigate how arboviruses target and enter cells. Our main arbovirus models are the phleboviruses Rift valley fever and Uukuniemi and, the flaviviruses West Nile and Zika. Through this research program, we expect to gain a detailed picture of the molecular and cellular mechanisms subverted by these viruses to infect humans.

 

Our virus picture gallery

 

Our virus movie gallery

 

Our recent contributions to the field

Glucosylceramide in bunyavirus particles is essential for virus binding to host cells
Uckeley ZM, Duboeuf M, Gu Y, Erny A, Mazelier M, Lüchtenborg C, Winter SL, Schad P, Mathieu C, Koch J, Boulant, S, Chlanda P, Maisse C, Brügger B, and Lozach PY.
2024, 81(1):71
Manuscript, Figure S1, Figure S2, Figure S3, Figure S4, Figure S5, Table S1, Table S2, Table S3, Table S4, Table S5, Table S6, Table S7
PhD thesis manuscript of Dr Zina M Uckeley

 

Illuminating bunyavirus entry into host cells with fluorescence
Gu Y and Lozach PY.
2023, in press
Manuscript

 

The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells
Koch J, Xin Q, Obr M, Schäfer A, Rolfs N, Anagho HA, Kudulyte A, Woltereck L, Kummer S, Campos J, Uckeley ZM, Bell-Sakyi L, Kräusslich HG, Schur FKM, Acuna C, and Lozach PY.
2023, 19(8):e1011562
Manuscript, Figure S1, Figure S2, Figure S3, Table S1, Movie S1, Movie S2, Movie S3, PDB1, PDB2
PhD thesis manuscript of Dr Jana Koch

 

The orthobunyavirus Germiston enters host cells from late endosomes
Windhaber S, Xin Q, Uckeley ZM, Koch J, Obr M, Garnier C, Luengo-Guyonnot C, Duboeuf M, Schur FKM, and Lozach PY.
2022, 96(5):e02146-21
Manuscript, Supplementary Information, Movie S1, Movie S2

 

Rift Valley fever virus: a new avenue of research on the biological functions of amyloids
Pen K and Lozach PY.
2021, 16(10):677-89
Manuscript

 

TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells
Koch J, Uckeley ZM, Doldan P, Stanifer M, Boulant S, and Lozach PY.
2021, 40(16):e107821
Manuscript, Figure EV1, Figure EV2, Figure EV3, Figure EV4, and Appendix

 

Orthobunyaviruses: from virus binding to penetration into mammalian host cells
Windhaber S, Qilin X, and Lozach PY.
2021, 13(5):872
Manuscript

 

Entry of phenuiviruses into mammalian host cells
Koch J, Qilin X, Tischler ND, and Lozach PY.
2021, 13(2):299
Manuscript

 

NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice
Léger P, Nachman E, Richter K, Tamietti C, Koch J, Burk R, Kummer S, Xin Q, Stanifer M, Bouloy M, Boulant S, Kräusslich HG, Montagutelli X, Flamand M, Nussbaum-Krammer C, and Lozach PY
2020, 11:3281
Manuscript, Supplementary Information, Movie S1, Movie S2, Movie S3

 

Novel Toscana virus reverse genetics system establishes NSs as an antagonist of type I interferon responses
Woelfl F, Léger P, Oreshkova N, Pahmeier F, Windhaber S, Koch J, Stanifer M, Roman Sosa G, Uckeley ZM, Rey FA, Boulant S, Kortekaas J, Wichgers Schreur PJ, and Lozach PY. (Bold indicates multiple corresponding authors)
2020, 12(4):400
Manuscript, Figures S1 to S3

 

Quantitative proteomics of Uukuniemi virus – host cell interactions reveals GBF1 as proviral host factor for phleboviruses
Uckeley ZM, Moeller R, Kühn LI, Nilsson E, Robens C, Lasswitz L, Lindqvist R, Lenman A, Passos V, Voss Y, Sommerauer C, Kampmann M, Goffinet C, Meissner F, Överby AK, Lozach PY, and Gerold G. (Bold indicates multiple corresponding authors)
2019, 18(12):2401-17
Highlighted in ASBMB Today
Manuscript, Figures S1 to S3, Figure S4, Table S1, Table S2, Table S3

 

Cell biology of phlebovirus entry
Uckeley ZM, Koch J, Tischler ND, Léger P, and Lozach PY
2019, 23(3):176-87
Manuscript

 

Deciphering virus entry with fluorescently labeled viral particles
Hoffmann AB, Mazelier M, Léger P, and Lozach PY
2018, 1836:159-83
Manuscript
PhD thesis manuscript of Dr Anja Hoffmann

 

Uukuniemi virus as a tick-borne virus model
Mazelier M, Rouxel RN, Zumstein M, Mancini R, Bell-Sakyi L, and Lozach PY
2016, 90:6784-98
Highlighted in Journal of Virology
Manuscript, M segment UUKV strain RVS, M segment UUKV strain HRS
PhD thesis manuscript of Dr Magalie Mazelier

 

Differential use of the C-type lectins L-SIGN and DC-SIGN for phlebovirus endocytosis
Léger P, Tetard M, Youness B, Cordes N, Rouxel RN, Flamand M, and Lozach PY
2016, 17:639-56
Manuscript, Movie S1, Movie S2

 

Early bunyavirus-host cell interactions
Albornoz A, Hoffmann A, Lozach PY, and Tischler ND, (Bold indicates multiple corresponding authors)
2016, 8(5)
Manuscript

 

Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis
Boulant S, Stanifer M, and Lozach PY, (Bold indicates multiple corresponding authors)
2015, 7:2794-815
Manuscript

 

Bunyaviruses: from transmission by arthropods to entry into mammalian-host first-target cells
Léger P and Lozach PY
2015, 10:859-81
Manuscript

 

Genome-wide siRNA screens reveal VAMP3 as a novel host factor required for Uukuniemi virus late penetration
Meier R, Franceschini A, Horvath P, Tetard M, Mancini R, von Mering C, Helenius A, and Lozach PY
2014, 88:8565-78
Highlighted in Future Virology, Journal of Virology, and Medecine Science.
Manuscript, Table S1, Table S2, Table S3, Table S4, Table S5, Table S6, Table S7, Table S8
PhD thesis manuscript of Dr Roger Meier

 

DC-SIGN as receptor for phleboviruses
Lozach PY, Kühbacher A, Meier R, Mancini R, Bitto D, Bouloy M, and Helenius A, (Bold indicates multiple corresponding authors)
2011, 10:75-88
Highlighted in Cell Host & Microbe, Current Opinion in Virology, F1000, Future Virology, and Medecine Science.
Manuscript, Supplementary Information, Movie S1, Movie S2, Movie S3, Movie S4, Movie S5, Movie S6