Affiliation:
1. Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
2. State Key Laboratory of Pathogen and Biosecurity, Beijing, China
3. State Key Laboratory of Virology, Wuhan University, Wuhan, China
Abstract
ABSTRACT
cis
-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved
cis
-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The
d
ownstream of 5′
c
yclization
s
equence (5′CS)
p
seudo
k
not (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5′CS, and the presence of DCS-PK facilitates the formation of 5′-3′ RNA complexes. Taken together, our results reveal that the
cis
-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other
cis
-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
68 articles.
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