Dr. Pierre-Yves Lozach

pierre-yves.lozach@med.uni-heidelberg.de

Phone: ++49-(0)6221–56-1328

Fax: ++49-(0)6221–56-5003

Cell Biology of Arboviral Infections

Projects

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. Arbovirus­es vir­tu­al­ly exist in any known habi­tat, and thus far, over 500 iso­lates have been iden­ti­fied through many dis­tinct viral fam­i­lies. Many arbovirus­es are impor­tant pathogens in live­stock and humans, caus­ing severe health prob­lems, often fatal, such as acute 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 Lozach group is to obtain a deep knowl­edge of the biol­o­gy of virus­es trans­mit­ted by mos­qui­toes and ticks, both in their arthro­pod vec­tors and in the mam­malian host. Our goal is to ful­ly under­stand the arthro­pod vec­tor-to-mam­mal 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 (i) char­ac­ter­ize arbovirus­es in both arthro­pod vec­tor cells and mam­malian host cells, (ii) inves­ti­gate how arbovirus­es tar­get and enter cells, and (iii) define the viral and host fac­tors respon­si­ble for vir­u­lence and lethal­i­ty. Our main arbovirus mod­els are the phle­bovirus­es Rift val­ley fever, Toscana, 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.

Fig­ure 1 | Research Pro­gram

Fig­ure 2 | Project i: Elec­tron micro­graph show­ing one par­ti­cle of Uuku­nie­mi virus.

Fig­ure 3 | Project ii: Uuku­nie­mi viral par­ti­cles (red) with­in LAM­P1-pos­i­tive endo­somes (green).

Fig­ure 4 | Project iii: The non­struc­tur­al pro­tein NSs (red) of Rift Val­ley fever virus ana­lyzed by super res­o­lu­tion microscopy

Selected Publications

Com­plete pub­li­ca­tion list (PubMed)

Uck­e­ley, Z.M., Moeller, R., Kühn, L.I., Nils­son, E., Robens, C., Lass­witz, L., Lindqvist, R., Len­man, A., Pas­sos, V., Voß, Y., Som­mer­auer, C., Kamp­mann, M., Goffinet, C., Meiss­ner, F., Över­by, A.K., Lozach, P.Y.† and Gerold, G.†. (2019). Quan­ti­ta­tive pro­teomics of Uuku­nie­mi virus-host cell inter­ac­tions reveals GBF1 as provi­ral host fac­tor for phle­bovirus­es. Mol. Cell. Pro­teomics in press, †designs cor­re­spond­ing authors.

Uck­e­ley, Z.M., Koch, J., Tis­chler, N.D., Léger, P., Lozach, P.Y. (2019). Cell biol­o­gy of phle­bovirus entry. Virolo­gie, 23(3):176–87.

Li, S., Zhu, X., Guan, Z., Huang, W., Kor­te­kaas, J., Lozach, P.Y. and Peng, K. (2019). NSs fil­a­ment for­ma­tion is impor­tant but not suf­fi­cient for RVFV vir­u­lence in vivo. Virus­es, 11(9).

Hoff­mann, A., Maze­li­er, M., Léger, P., and Lozach, P.Y. (2018). Deci­pher­ing virus entry with flu­o­res­cent­ly labeled viral par­ti­cles. Meth­ods Mol. Biol., 1836:159–183.

Lozach, P.Y. (2018). Ear­ly virus-host cell inter­ac­tions. J. Mol. Biol., 430(17):2555–2556.

Ashtikar, M., Mäder, K., Klein, K., Wun­der­lich, K., Lozach, P.Y., Gao, F., Mende, S., Strass­er, C., Den­ni­son, T., Marenchi­no, M., Wack­er, M.G. (2018). LOEWE work­shop par­ti­cle char­ac­ter­i­za­tion in med­i­cine and biol­o­gy. Pharm. Front. 1: pii: e190002

Maze­li­er, M., Roux­el, R.N., Zum­stein, M., Manci­ni, R., Bell-Sakyi, L., and Lozach, P.Y. (2016). Uuku­nie­mi virus as a tick-borne virus mod­el. J. Virol., 90:6784–98.

Albor­noz, A.†, Hoff­mann, A.†, Lozach, P.Y., Tis­chler, N.D. (2016). Ear­ly bun­yavirus-host cell inter­ac­tions. Virus­es 8(5): pii: e143

Léger, P.†, Tetard, M.†, Youness, B., Cordes, N., Roux­el, R.N., Fla­mand, M., and Lozach, P.Y. (2016). Dif­fer­en­tial use of the C‑type lectins L‑SIGN and DC-SIGN for phle­bovirus endo­cy­to­sis. Traf­fic, 17:639–656.

Boulant, S.†, Stan­i­fer, M., and Lozach, P.Y.† (2015). Dynam­ics of virus-recep­tor inter­ac­tions in virus bind­ing, sig­nal­ing, and endo­cy­to­sis. Virus­es, 7:2794–2815.

Léger, P. and Lozach, P.Y. (2015). Bun­yavirus­es: from trans­mis­sion by arthro­pods to entry into mam­malian-host first-tar­get cells. Future Virol., 10:859–881.

Meier, R., Maze­li­er, M., and Lozach, P.Y. (2015). High-through­put small inter­fer­ing RNA screens: When small inter­fer­ing RNAs behave like microR­NA. Med. Sci., 31:247–249.

Acuña, R., Bignon, E., Manci­ni, R., Lozach, P.Y., and Tis­chler, N.D. (2015). Acid­i­fi­ca­tion trig­gers Andes han­tavirus mem­brane fusion and rearrange­ment of Gc into a sta­ble post-fusion homotrimer. J. Gen. Virol., 96:3192–7.

Meier, R., Frances­chi­ni, A., Hor­vath, P., Tetard, M., Manci­ni, R., von Mer­ing, C., Hele­nius, A., and Lozach, P.Y. (2014). Genome-wide siR­NA screens reveal VAMP3 as a nov­el host fac­tor required for Uuku­nie­mi virus late pen­e­tra­tion. J. Virol., 88:8565–8578.

Acuña, R., Cifuentes-Muñoz, N., Mar­quez, C.L., Bulling, M., Klingström, J., Manci­ni, R., Lozach, P.Y., and Tis­chler, N.D. (2014). Han­tavirus Gn and Gc gly­co­pro­teins self-assem­ble into virus-like par­ti­cles. J. Virol., 88:2344–2348.

Goncalves, A.R., Moraz, M.L., Pasqua­to, A., Hele­nius, A., Lozach, P.Y., and Kunz, S. (2013). Role of DC-SIGN in Las­sa virus entry into human den­drit­ic cells. J. Virol., 87:11504–11515.

Mer­cer, J., and Lozach, P.Y. (2013). Cel­lu­lar pro­tein dis­pos­al sys­tem assists poxvirus genome uncoat­ing. Med. Sci., 29:561–563.

Bar­ri­ga, G.P., Martínez-Valdeben­i­to, C., Galeno, H., Fer­rés, M., Lozach, P.Y., and Tis­chler, N.D. (2013). A rapid method for infec­tiv­i­ty titra­tion of Andes han­tavirus using flow cytom­e­try. J. Virol. Meth­ods, 193:291–294.

Lozach, P.Y.†, Küh­bach­er, A., Meier, R., Manci­ni, R., Bit­to, D., Bouloy, M., and Hele­nius, A.† (2011). DC-SIGN as recep­tor for phle­bovirus­es. Cell Host Microbe, 10:75–88.