Characterizing the Role of the Herpes Simplex Virus Type 2 UL21 Protein in Viral Nuclear Egress

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Date
2015-07-17
Authors
Nassiri, Arash
Keyword
Herpes Simplex Virus Type 2 , Nuclear Egress
Abstract
The herpes simplex virus type 2 (HSV-2) is an important human pathogen that is the main cause of genital herpes infections and has a significant and wide-ranging impact on human health. HSV-2 infections are one of the most common sexually transmitted diseases and are highly prevalent worldwide, thus making understanding their infection mechanisms all the more relevant. The UL21 gene, which is conserved amongst members of the Alphaherpesvirinae subfamily, encodes a tegument protein that is essential for HSV-2 propagation. More specifically, UL21 plays a critical role in the primary envelopment of capsids during nuclear egress, however the precise mechanism by which it does this is unclear. To investigate the role of UL21 in HSV-2 nuclear egress, we focused on events upstream of primary envelopment. First, we examined the role of UL21 in disrupting the localization of nuclear lamins during infection. Nuclear rim localization of lamins A, C, B1, and B2 was indistinguishable between the wild-type (WT), UL21 null (∆UL21), or repaired (∆UL21R) HSV-2 strains, suggesting UL21 is not implicated in the disassembly of nuclear lamins at the nuclear membrane. Additionally, UL21 did not influence the localization of the nuclear egress complex (NEC), composed of UL31 and UL34, insofar as cellular and virally-encoded UL31 and UL34 localization patterns were indistinguishable between the UL21 null, and repaired or wild-type strains. Lastly, in an attempt to characterize interacting partners for UL21, we focused on proteins implicated in nuclear egress or proteins that may function to recruit UL21 to the nuclear membrane, where it may carry out its essential role(s). While no interactions were detected between UL21 and key mediators of primary envelopment including UL31, UL34, or Us3, UL21 localization at the nuclear rim was enhanced by the overexpression of the inner nuclear membrane protein, LAP2β, suggesting a potential interaction between the two proteins. However, more experiments are warranted before any conclusive remarks can be made regarding such interaction. Taken together, these data have shed light on HSV-2 nuclear egress and have eliminated possible theories regarding the role of UL21 in HSV-2 primary envelopment.
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