Role of the small GTPase Rab27a during Herpes simplex virus infection of oligodendrocytic cells

Abstract

BackgroundThe morphogenesis of herpes simplex virus type 1 (HSV-1) comprises several events, of which some are not completely understood. It has been shown that HSV-1 glycoproteins accumulate in the trans-Golgi network (TGN) and in TGN-derived vesicles. It is also accepted that HSV-1 acquires its final morphology through a secondary envelopment by budding into TGN-derived vesicles coated with viral glycoproteins and tegument proteins. Nevertheless, several aspects of this process remain elusive. The small GTPase Rab27a has been implicated in regulated exocytosis, and it seems to play a key role in certain membrane trafficking events. Rab27a also seems to be required for human cytomegalovirus assembly. However, despite the involvement of various Rab GTPases in HSV-1 envelopment, there is, to date, no data reported on the role of Rab27a in HSV-1 infection.ResultsHerein, we show that Rab27a colocalized with GHSV-UL46, a tegument-tagged green fluorescent protein-HSV-1, in the TGN. In fact, this small GTPase colocalized with viral glycoproteins gH and gD in that compartment. Functional analysis through Rab27a depletion showed a significant decrease in the number of infected cells and viral production in Rab27a-silenced cells.ConclusionsAltogether, our results indicate that Rab27a plays an important role in HSV-1 infection of oligodendrocytic cells.

Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at thetrans-Golgi Network To Promote Virus Replication

“…Depletion of Rab1 and Rab43 results in decreased viral assembly, although this may be partially explained by indirect effects, such as decreased processing of glycoproteins and their impaired transport to the TGN in the absence of Rab1 and extensive disruption to the TGN structure upon depletion of Rab43 (147). Similar to what we observed with WDR11, Rab27a, which is involved in exocytosis and membrane trafficking (148), has been found to colocalize with HSV proteins at the TGN and increase viral yields and has therefore been suggested to play a role in HSV morphogenesis and/or egress (149).…”

Herpes Simplex Virus 1 Infection Induces Activation and Subsequent Inhibition of the IFI16 and NLRP3 Inflammasomes

“…1). Therefore, HSV-1 may be recruiting Rab GTPases from cellular functions to play roles in viral assembly, consistent with the model set forth by Bello-Morales et al (90) of the recruitment of Rab GTPases to the endoplasmic reticulum (ER) and Golgi compartment, where they colocalize with HSV-1 viral glycoproteins, gD and gH, though the mechanism of recruitment is unclear.…”

“…Previous studies suggest that the Rab GTPases are necessary for HSV-1 assembly and egress (88)(89)(90). Our data show that IL-1␤ transiently associates with Rab27a-containing vesicles and then remains in the cytoplasm in punctate spots while Rab27a is relocalized to a perinuclear region (Fig.…”

The Role of HTLV-1 in Alteration of Immune Regulation Through Regulatory T Cell Dysfunction and Exosomal Manipulation

“…Herpes simplex virus 1 (HSV1) is yet another virus that interacts with Rab27a. The interaction occurred through GSSHV-UL46, a viral tegument protein, in oligodendrocytes [86]. Viral glycoproteins gH and gD also interacted with Rab27a, and the importance of this association with Rab27a was proven in this paper by a decrease in viral production with Rab27a knockdown [86].…”

“…The interaction occurred through GSSHV-UL46, a viral tegument protein, in oligodendrocytes [86]. Viral glycoproteins gH and gD also interacted with Rab27a, and the importance of this association with Rab27a was proven in this paper by a decrease in viral production with Rab27a knockdown [86]. Whether this involved a decrease in exosome production, and how important this was for the lifecycle of HSV1, was not discussed at that time.…”