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Wu, Haoming; Wang, J. F.; Zhang, C. Y.; Fu, Lin; Pan, Zishu; Wang, N.; Zhang, P. W.; Zhao, Weiguang

doi:10.1023/a:1011187413930

Cited by 34 publications

(11 citation statements)

References 19 publications

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“…The highly virulent CSFV strain Margarita, likely the parental strain of the PdR virus (9), also carries the standard 5 uridines at this position. However, a similar 6-to 32-nucleotide-long uridine-rich insertion was found in the 3= UTR of several attenuated CSF vaccine virus strains, but this sequence was located approximately 90 nucleotides upstream of the PdR poly-U insertion (10,11). Previous studies showed that the 3= UTR of flaviviruses are implicated in virus replication (12,13).…”

mentioning

confidence: 79%

A Polyuridine Insertion in the 3′ Untranslated Region of Classical Swine Fever Virus Activates Immunity and Reduces Viral Virulence in Piglets

Wang

Liniger

Muñoz-González

et al. 2020

J Virol

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Low-virulence classical swine fever virus (CSFV) strains make CSF eradication particularly difficult. Few data are available on the molecular determinants of CSFV virulence. The aim of the present study was to assess a possible role for CSFV virulence of a unique, uninterrupted 36-uridine (poly-U) sequence found in the 3′ untranslated region (3′ UTR) of the low-virulence CSFV isolate Pinar de Rio (PdR). To this end, a pair of cDNA-derived viruses based on the PdR backbone were generated, one carrying the long poly-U insertion in the 3′ UTR (vPdR-36U) and the other harboring the standard 5 uridines at this position (vPdR-5U). Two groups of 20 5-day-old piglets were infected with vPdR-36U and vPdR-5U. Ten contact piglets were added to each group. Disease progression, virus replication, and immune responses were monitored for 5 weeks. The vPdR-5U virus was significantly more virulent than the vPdR-36U virus, with more severe disease, higher mortality, and significantly higher viral loads in serum and body secretions, despite similar replication characteristics in cell culture. The two viruses were transmitted to all contact piglets. Ninety percent of the piglets infected with vPdR-36U seroconverted, while only one vPdR-5U-infected piglet developed antibodies. The vPdR-5U-infected piglets showed only transient alpha interferon (IFN-α) responses in serum after 1 week of infection, while the vPdR-36U-infected piglets showed sustained IFN-α levels during the first 2 weeks. Taken together, these data show that the 3′ UTR poly-U insertion acquired by the PdR isolate reduces viral virulence and activates the innate and humoral immune responses without affecting viral transmission. IMPORTANCE Classical swine fever (CSF), a highly contagious viral disease of pigs, is still endemic in some countries of Asia and Central and South America. Considering that the 3′ untranslated region (3′ UTR) plays an important role in flavivirus replication, the present study showed for the first time that a long polyuridine sequence acquired in the 3′ UTR by an endemic CSFV isolate can activate immunity, control viral replication, and modulate disease in piglets. Our findings provide new avenues for the development of novel vaccines against infections with CSF virus and other flaviviruses. Knowledge of molecular virulence determinants is also relevant for future development of rapid and efficient diagnostic tools for the prediction of the virulence of field isolates and for efficient CSF control.

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mentioning

confidence: 79%

A Polyuridine Insertion in the 3′ Untranslated Region of Classical Swine Fever Virus Activates Immunity and Reduces Viral Virulence in Piglets

Wang

Liniger

Muñoz-González

et al. 2020

J Virol

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“…Three complete genomes of CSFV were previously sequenced by our laboratory (AF407339, AF091507, and AF092448) [18,19]. The other available complete CDS of CSFV were downloaded from GenBank in March 2008 and sequences with [99% sequence identities were excluded.…”

Section: Methodsmentioning

confidence: 99%

“…The other available complete CDS of CSFV were downloaded from GenBank in March 2008 and sequences with [99% sequence identities were excluded. A total of 35 CSFV genomes [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] representing 6 subgenotypes (1.1, 1.2, 2.1, 2.2, 2.3, and 3.4) and all 3 kinds of virulence (highly virulent strains, moderated virulent strains, and avirulent strains) were used in this study. The genotyping of 35 CSFV genomes was performed using the CSFV sequence database (http://viro08.tiho-hannover.…”

Section: Methodsmentioning

confidence: 99%

Analysis of synonymous codon usage in classical swine fever virus

et al. 2008

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Using the complete genome sequences of 35 classical swine fever viruses (CSFV) representing all three genotypes and all three kinds of virulence, we analyzed synonymous codon usage and the relative dinucleotide abundance in CSFV. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in CSFV. Furthermore, we observed that the relative abundance of dinucleotides in CSFV is independent of the overall base composition but is still the result of differential mutational pressure, which also shapes codon usage. In addition, other factors, such as the subgenotypes and aromaticity, also influence the codon usage variation among the genomes of CSFV. This study represents the most comprehensive analysis to date of CSFV codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias.

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“…Although those mutations in E2 of Thiverval are not crucial mutations in virulence as that found in Brescia, they may cooperatively affect virulence of CSFV Thiverval strain. A 12-14 nucleotide (nt) T-rich insertion in the 3 0 -UTR can be found in most attenuated vaccine strains of classical swine fever, such as HCLV, C-strain, Porcivac, Ravoc, and Russian LK [13,14,34]. In this work, we found a significant difference among the 3 0 -UTR nucleotide sequences of Alfort A19, Alfort/187, and Thiverval vaccine strains.…”

Section: Discussionmentioning

confidence: 59%

“…The complete viral genomes of HCLV and GPE -vaccine strains were sequenced [12][13][14]. Understanding the genome sequences of these CSFV strains provides insight into the pathogenicity and the attenuation of the viruses.…”

Section: Introductionmentioning

confidence: 99%

Complete genome sequence of attenuated low-temperature Thiverval strain of classical swine fever virus

Zhao

et al. 2008

Virus Genes

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The Thiverval vaccine strain of classical swine fever virus (CSFV) was derived from virulent Alfort strain through the serial passages in cells at 29-30 degrees C. In this study, we determined the complete genome sequence of this strain and found that its genome contains one open reading frame (ORF) that encodes a polyprotein with 3,898 amino acids. The 5'-UTR of Thiverval is 373 nt long with only one mutation at position 220. In contrast, the length of 3'-UTR is highly heterogeneous ranging from 233 to 259 bp. The heterogeneity of length of the 3'-UTR was due to an insertion of a variable length of T-rich sequence ranging from 6 to 32 nt. The insertion may change the structure and free energy of the 3'-UTR, resulting in a destabilization of the 3'-UTR. Sequence alignment of Thiverval and other CSFV strains showed 85.2-99.6% identities at the nucleotide level and 92.5-99.5% at the amino acid level. The phylogenetic tree analysis of the complete ORF, partial region of E2, and NS5B suggests that the CSFV Thiverval strain belongs to genetic group 1 and subgroup 1.1. The results from this study provide insight into the molecular mechanism of the attenuation of Thiverval vaccine strain.

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Cited by 34 publications

References 19 publications

A Polyuridine Insertion in the 3′ Untranslated Region of Classical Swine Fever Virus Activates Immunity and Reduces Viral Virulence in Piglets

A Polyuridine Insertion in the 3′ Untranslated Region of Classical Swine Fever Virus Activates Immunity and Reduces Viral Virulence in Piglets

Analysis of synonymous codon usage in classical swine fever virus

Complete genome sequence of attenuated low-temperature Thiverval strain of classical swine fever virus

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