Abstract
The recently identified Luman/CREB3-binding partner LRF (Luman/CREB3 recruitment factor) was shown to localize to discrete sub-nuclear foci. Luman is implicated in herpes simplex virus-1 (HSV-1) latency/reactivation and the unfolded protein response (UPR) pathway; therefore, we sought to characterize the formation of the LRF nuclear foci in the context of cellular signaling and HSV-1 replication. Here, we mapped the nuclear foci-targeting sequence to the central region containing the first leucine zipper (a.a.415-519), and found that the integrity of the whole region appears essential for LRF foci formation. LRF foci integrity was unaffected by inhibition of cellular DNA replication and translation, however, disruption of transcription resulted in altered LRF localization. When compared to other cellular and viral foci LRF co-localized with the nuclear receptor co-activator GRIP1, while the HSV-1 gene products ICP4, ICP27 and VP13/14 disrupted foci formation to varying degrees. Interestingly, cells over-expressing LRF were resistant to productive HSV-1 infection and this resistance was dependent upon protein targeting and an N-terminal transactivation domain. When LRF knockdown cells were subjected to primary infection, HSV-1 gene expression and progeny virus yield were enhanced by ∼3 fold compared to wildtype cells. Taken together, these results indicate that LRF is a key regulator that may act direct or indirectly as a repressor of essential genes required for productive viral infection.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.