LSm1 binds to the Dengue virus RNA 3′ UTR and is a positive regulator of Dengue virus replication

Abstract

Dengue virus (DENV) is a mosquito-transmitted flavivirus that can cause severe disease in humans. The DENV positive strand RNA genome contains 5' and 3' untranslated regions (UTRs) that have been shown to be required for virus replication and interaction with host cell proteins. In the present study LSm1 was identified as a host cellular protein involved in DENV RNA replication. By using two independent methodologies, we demonstrated a critical interaction between LSm1 and the 3' UTR of DENV. Furthermore, the confocal immunofluorescence analysis showed that the interaction between LSm1 and viral RNA is located in P-body around nucleoli in the cytoplasm. LSm1 knockdown by siRNA specifically reduced the levels of viral RNA in DENV-infected cells and infectious DENV particles in the supernatant. These results provide evidence that LSm1 binding to the DENV RNA 3' UTR positively regulates DENV RNA replication.

Strategies for Success. Viral Infections and Membraneless Organelles

“…Similarly, DENV infection reduces PBs accumulation through an interaction of DENV 3′UTR with DDX6 (Ward et al, 2011). In addition, it has been shown that Dcp1b colocalizes with viral dsRNA, suggesting that DENV RNA replication occurs within PBs (Dong et al, 2015). LSm1, another PBs component, interacts with DENV RNA both in vitro and in vivo during DENV-2 infection, colocalizing with sites of viral replication (Dong et al, 2015).…”

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

“…They also show that flaviviruses can use the genome cyclation for regulating transitions between different steps of the infective cycle. Finally, host proteins related to mRNA splicing such as hnRNPA2 (Katoh et al, 2011) or Lsm1 (Dong et al, 2015) interact with the cyclization sequence motifs and/or with functional RNA domains located in the untranslated regions. The recruitment of these proteins is required for and efficient viral replication process though their molecular mechanism is still unknown.…”

Biochemistry and Molecular Biology of Flaviviruses

“…The same result was observed with DENV2 and WNV infection when LSM1, another component of P bodies that also interacts with the DENV 3′UTR, was silenced. 391,417 Additionally, the DEDD RNA exonuclease ERI3 binds to the 3′UTRs of DENV and YFV and is required for viral RNA synthesis. 283 In summary, although the functional significance for many of these RBPs has been established, understanding the detailed molecular mechanisms by which these RBPs contribute to viral propagation requires further investigation.…”