Y‐shaped RNA secondary structure of a noncoding region in the genomic RNA of tick‐borne encephalitis virus affects pathogenicity

Abstract

Tick‐borne encephalitis virus (TBEV) is a zoonotic virus that causes encephalitis in humans. Various deletions have been reported in a variable region of the 3′ untranslated region of the TBEV genome. This study analyzed the role of a Y‐shaped secondary structure in the pathogenicity of TBEV by using reverse genetics. Deletion of the structure increased the mortality rate of virus‐infected mice but did not affect the virus multiplication in cultured cells and organs. The results indicate that the secondary structure is involved in the regulation of TBEV pathogenesis.

Functional characterization of 5′ untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells

“…The latter has been confirmed experimentally [ 21 , 32 ]. Using the linear model, a conserved Y-shaped conformation was predicted for all 5′UTRs [ 12 , 26 ]. This contained a double-stranded stem (stem zero, S0) split into two stem-loop (SL) structures, SL1 and SL2 ( Fig 1A ) This folds independently of other downstream RNA structures and the dsRNA cyclization stem in the cyclization model [ 19 , 32 ].…”

“…However, the evolutionary conservation of SL2 provides clues to its role within invertebrate hosts (ticks). The region proceeding the dsRNA S0 within SLA shows higher conservation amongst all flaviviruses forming, SL3 [ 21 , 22 , 26 ] (or SLB) in the linear model, and the dsRNA stem in the cyclization model. This is predicted to mediate the interaction between the 5’UTR and 3’UTR.…”

“…Secondary RNA structures within the 5’ and 3’UTRs regulate the rate of virus replication, RNA polarity, and genome encapsidation [ 19 , 23 , 24 ]. Y-shaped structures within three major thermodynamically stable structural elements of the 5’UTR have been predicted through simulations of secondary RNA folding for tick- and mosquito-borne flaviviruses (TBFV, MBFV) [ 25 , 26 ]. These include stem (S0) and two branching stem-loop structures 1 (SL1) and 2 (SL2) ( Fig 1A ).…”