Naslov
MCMV affects endosomal recycling by alteration Rab/Arf cascade in infected fibroblasts

Autori
Mahmutefendić Lučin, Hana ; Karleuša, Ljerka ; Blagojević Zagorac, Gordana ; Grabušić, Kristina ; Pavišić, Valentino ; Jug, Natalia ; Marcelić, Marina ; Lukanović Jurić, Silvija ; Lučin, Pero

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book: 2018 Annual Meeting of Croatian Immunological Society / - , 2018, 17-17

Skup
Annual Meeting of the Croatian Immunological Society 2018

Mjesto i datum
Zadar, Hrvatska, 19.10.2018. - 20.10.2018

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Assembly compartment ; Endosomal recycling ; Murine cytomegalovirus ; Rab proteins ; Sorting endosomes ; Transferrin receptor

Sažetak
The final goal of any virus is to exploit the cell for its own replication. With that purpose, cytomegalovirus (CMV) induce remodeling of cellular compartments. The whole process is finalized with the formation of the viral assembly compartment (VAC, viral factory). However, that cellular perturbation results with the disturbance of the normal cellular function, primarily considering its endosomal transport. Therefore, the elucidation of the processes that influence the cellular physiology can help us to understand the mechanisms that virus uses in order to prepare the formation of VAC. The perturbation of cellular endosomal system takes place very early in the infection (6 hrs p.i.), and is featured with the formation of the EPERC (early-phase endosomal retention compartment). That juxtanuclear (JN) compartment arise as the result of restructuring of early endosomes (EE), endosomal recycling compartment (ERC), and trans-Golgi network (TGN). Normally, the transport through those cellular compartments is very precisely regulated by the Rab/Arf cascades and loops. Rab and Arf proteins belong to the group of the small GTPases that could exists in their GTP (active), or GDP (inactive) form. Therefore, the target of viral activity, when many of cellular molecules that are transported through sorting endosomes (SE) accumulate in EPERC, should be searched for between those molecules. Furthermore, due to the viral interference in normal regulation of endocytic flow, the recycling pathways are also inhibited, and transferrin receptor (TfR), MHC- I molecules (MHC-I), Rae-1, and NBD- sphyngomyelin (NBD-SM) are retained juxtanuclearly. The kinetic studies and mathematic modeling have shown that fast and slow recycling pathways are targeted, but not the ultra-rapid recycling. Considering retention of specific Rab and Arf molecules in remodeled JN compartment, as well as the amount of their total cellular expression, we have concluded that MCMV targets the Arf6/Rab35 loop and Rab35 effectors (MICAL- L1, Rab13, Rab10, Rab36, Rab8, EHD1), but also, very probably, the Rab11-Rab8/Rab10 activation cascade, and Rab4-Arl1-Arf1/Arf3 cascade. Those MCMV interventions includes: locking of small GTPase into permanently active (GTP), or permanently inactive (GDP) form, loss of GTPase from the cell membrane, etc. The final result is the inhibition of endosomal flow, including also the process of recycling. Therefore, we can conclude that MCMV interference with Rab/Arf cascade issue with inhibition of cellular recycling. The side effect of that process is also the immunoevasive effect of CMV infection due to downregulation of MHC-I and Rae-1 molecules.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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