Identification and characterization of the short variable region of the Japanese encephalitis virus 3′ NTR

Kato, Fumihiro; Kotaki, Akira; Yamaguchi, Yukie; Shiba, Hiroshi; Hosono, Kuniaki; Harada, Seiya; Saijo, Masayuki; Kurane, Ichiro; Takasaki, Tomohiko; Tajima, Shigeru

doi:10.1007/s11262-011-0685-6

Cited by 9 publications

(6 citation statements)

References 34 publications

(59 reference statements)

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“…The 3′VR starts immediately downstream of the stop codon of the viral ORF and upstream of the conserved region and is extremely heterogeneous in both length and sequence in natural isolates [ 90 , 91 , 92 ]. The role of 3′VR is more elusive than other regions of the UTRs and is generally thought of as an enhancer element.…”

Section: Effects Of the Untranslated Regions (Utrs) On Virulencementioning

confidence: 99%

Viral Determinants of Virulence in Tick-Borne Flaviviruses

Kellman¹,

Offerdahl²,

Melik

et al. 2018

Viruses

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Tick-borne flaviviruses have a global distribution and cause significant human disease, including encephalitis and hemorrhagic fever, and often result in neurologic sequelae. There are two distinct properties that determine the neuropathogenesis of a virus. The ability to invade the central nervous system (CNS) is referred to as the neuroinvasiveness of the agent, while the ability to infect and damage cells within the CNS is referred to as its neurovirulence. Examination of laboratory variants, cDNA clones, natural isolates with varying pathogenicity, and virally encoded immune evasion strategies have contributed extensively to our understanding of these properties. Here we will review the major viral determinants of virulence that contribute to pathogenesis and influence both neuroinvasiveness and neurovirulence properties of tick-borne flaviviruses, focusing particularly on the envelope protein (E), nonstructural protein 5 (NS5), and the 3′ untranslated region (UTR).

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Section: Effects Of the Untranslated Regions (Utrs) On Virulencementioning

confidence: 99%

Viral Determinants of Virulence in Tick-Borne Flaviviruses

Kellman¹,

Offerdahl²,

Melik

et al. 2018

Viruses

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“…The length and sequence of this region varies significantly between different arthropod-borne flaviviruses (Kato, Kotaki et al 2012). One to three copies of a repeated conserved sequence (RYF) are present in the VRs of different natural isolates of YFV and in some non-vector flaviviruses (Gritsun and Gould 2007).…”

Section: Additional Conserved 3′ Ncr Sequencesmentioning

confidence: 99%

Functions of the 3′ and 5′ genome RNA regions of members of the genus Flavivirus

Brinton

Basu

2015

Virus Research

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The positive sense genomes of members of the genus Flavivirus in the family Flaviviridae are ~11 kb nts in length and have a 5′ type I cap but no 3′ poly A. The 5′ and 3′ terminal regions contain short conserved sequences that are proposed to be repeated remnants of an ancient sequence. However, the functions of most of these conserved sequences have not yet been determined. The terminal regions of the genome also contain multiple conserved RNA structures. Functional data for many of these structures has been obtained. Three sets of complementary 3′ and 5′ terminal region sequences, some of which are located in conserved RNA structures, interact to form a panhandle structure that is required for initiation of minus strand RNA synthesis with the 5′ terminal structure functioning as the promoter. How the switch from the terminal RNA structure base pairing to the long distance RNA-RNA interaction is triggered and regulated is not well understood but evidence suggests involvement of a cell protein binding to three sites on the 3′ terminal RNA structures and a cis-acting metastable 3′ RNA element in the 3′ terminal structure. Cell proteins may also be involved in facilitating exponential replication of nascent genomic RNA within replication vesicles at later times of infection cycle. Other conserved RNA structures and/or sequences in the 5′ and 3′ terminal regions have been proposed to regulate genome translation. Additional functions of the 5′ and 3′ terminal sequences have also been reported.

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“…The 3′UTR is dispensable for the replication of dengue type 1 virus in vitro (Tajima et al, 2006 ). The variable area in the 3' UTR of Japanese encephalitis virus (JEV) reportedly did not affect its growth in vitro or its pathogenicity in mice (Kato et al, 2012 ). However, a previous report showed that the variable area of DENV-2 can enhance viral replication in baby hamster kidney cells, although this area is dispensable in mosquito cells (Alvarez et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Complete Genome Characterization of the 2017 Dengue Outbreak in Xishuangbanna, a Border City of China, Burma and Laos

Wen

Ma²,

Lin

et al. 2018

Front. Cell. Infect. Microbiol.

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A dengue outbreak abruptly occurred at the border of China, Myanmar, and Laos in June 2017. By November 3rd 2017, 1184 infected individuals were confirmed as NS1-positivein Xishuangbanna, a city located at the border. To verify the causative agent, complete genome information was obtained through PCR and sequencing based on the viral RNAs extracted from patient samples. Phylogenetic trees were constructed by the maximum likelihood method (MEGA 6.0). Nucleotide and amino acid substitutions were analyzed by BioEdit, followed by RNA secondary structure prediction of untranslated regions (UTRs) and protein secondary structure prediction in coding sequences (CDSs). Strains YN2, YN17741, and YN176272 were isolated from local residents. Stains MY21 and MY22 were isolated from Burmese travelers. The complete genome sequences of the five isolates were 10,735 nucleotides in length. Phylogenetic analysis classified all five isolates as genotype I of DENV-1, while isolates of local residents and Burmese travelers belonged to different branches. The three locally isolates were most similar to the Dongguan strain in 2011, and the other two isolates from Burmese travelers were most similar to the Laos strain in 2008. Twenty-four amino acid substitutions were important in eight evolutionary tree branches. Comparison with DENV-1SS revealed 658 base substitutions in the local isolates, except for two mutations exclusive to YN17741, resulting in 87 synonymous mutations. Compared with the local isolates, 52 amino acid mutations occurred in the CDS of two isolates from Burmese travelers. Comparing MY21 with MY22, 17 amino acid mutations were observed, all these mutations occurred in the CDS of non-structured proteins (two in NS1, 10 in NS2, two in NS3, three in NS5). Secondary structure prediction revealed 46 changes in the potential nucleotide and protein binding sites of the CDSs in local isolates. RNA secondary structure prediction also showed base changes in the 3′UTR of local isolates, leading to two significant changes in the RNA secondary structure. To our knowledge, this study is the first complete genome analysis of isolates from the 2017 dengue outbreak that occurred at the border areas of China, Burma, and Laos.

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Identification and characterization of the short variable region of the Japanese encephalitis virus 3′ NTR

Cited by 9 publications

References 34 publications

Viral Determinants of Virulence in Tick-Borne Flaviviruses

Viral Determinants of Virulence in Tick-Borne Flaviviruses

Functions of the 3′ and 5′ genome RNA regions of members of the genus Flavivirus

Complete Genome Characterization of the 2017 Dengue Outbreak in Xishuangbanna, a Border City of China, Burma and Laos

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