Removal of the E
            <sup>rns</sup>
            RNase Activity and of the 3′ Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease

Wang, Miaomiao; Bohórquez, José Alejandro; Muñoz-González, Sara; Gerber, Marlène; Alberch, Mònica; Pérez‐Simó, Marta; Abad, Xavier; Liniger, Matthias; Ruggli, Nicolas; Ganges, Llilianne

doi:10.1128/jvi.00438-22

Cited by 3 publications

(4 citation statements)

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“…Nevertheless, attenuation due to a poly-U sequence in the 3′UTR cannot be excluded, since the introduction of 12 uridines in the 3′UTR of the virulent Shimen backbone attenuated the virus [ 64 ]. In line with this, we have shown that the virulence of PdR with RNase-negative E rns was drastically enhanced in piglets when the poly-U sequence was removed [ 19 ]. Only a few studies show synergistic effects between E2 and other viral elements for gain of virulence in pigs.…”

Section: Discussionmentioning

confidence: 75%

“…In addition, in 3-month-old pigs, we did not observe any persistence of vPdR-36U, contrasting with the persistence of PdR described in piglets infected at birth [ 20 ]. Age-related differences in disease severity were also observed when a virulent E rns mutant PdR (vPdR-H 30 K-5U) was assessed in 3-week-old pigs in comparison with 5-day-old piglets [ 19 ]. Taken together, these data suggest a non-negligible contribution of age, genetic background, and hygiene status of the host to the virulence phenotype observed.…”

Section: Discussionmentioning

confidence: 99%

“…The severity of CSF is also dependent on host factors such as genetic background, immune status and age [ 17 , 18 ]. Notably, age-related differences were observed experimentally with 5-day-old versus 3-week-old pigs [ 19 ]. Moreover, infections of newborn piglets with low-virulent strains can result in persistent infections with high viral load and delayed or lack of seroconversion [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence

Hinojosa,

Liniger,

García-Nicolás

et al. 2024

Viruses

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Classical swine fever (CSF) has been eradicated from Western and Central Europe but remains endemic in parts of Central and South America, Asia, and the Caribbean. CSF virus (CSFV) has been endemic in Cuba since 1993, most likely following an escape of the highly virulent Margarita/1958 strain. In recent years, chronic and persistent infections with low-virulent CSFV have been observed. Amino acid substitutions located in immunodominant epitopes of the envelope glycoprotein E2 of the attenuated isolates were attributed to positive selection due to suboptimal vaccination and control. To obtain a complete picture of the mutations involved in attenuation, we applied forward and reverse genetics using the evolutionary-related low-virulent CSFV/Pinar del Rio (CSF1058)/2010 (PdR) and highly virulent Margarita/1958 isolates. Sequence comparison of the two viruses recovered from experimental infections in pigs revealed 40 amino acid differences. Interestingly, the amino acid substitutions clustered in E2 and the NS5A and NS5B proteins. A long poly-uridine sequence was identified previously in the 3′ untranslated region (UTR) of PdR. We constructed functional cDNA clones of the PdR and Margarita strains and generated eight recombinant viruses by introducing single or multiple gene fragments from Margarita into the PdR backbone. All chimeric viruses had comparable replication characteristics in porcine monocyte-derived macrophages. Recombinant PdR viruses carrying either E2 or NS5A/NS5B of Margarita, with 36 or 5 uridines in the 3′UTR, remained low virulent in 3-month-old pigs. The combination of these elements recovered the high-virulent Margarita phenotype. These results show that CSFV evolution towards attenuated variants in the field involved mutations in both structural and non-structural proteins and the UTRs, which act synergistically to determine virulence.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence

Hinojosa,

Liniger,

García-Nicolás

et al. 2024

Viruses

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“…Classical swine fever (CSF), one of the most important viral diseases in domestic pigs and wild boars, is notifiable to the World Organization for Animal Health (WOAH) [ 1 , 2 ]. CSF is caused by an enveloped, single-stranded RNA virus belonging to the genus Pestivirus in the family Flaviviridae [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Optimized protocol for double vaccine immunization against classical swine fever and porcine reproductive and respiratory syndrome

Liu

Shan

et al. 2023

BMC Vet Res

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Background Classical swine fever and porcine reproductive and respiratory syndrome have seriously affected the development of the swine breeding industry in China. Vaccine immunization remains the main way to prevent these infections. The aim of this study was to establish an optimized protocol for vaccine immunization against classical swine fever virus (CSFV) and porcine reproductive and respiratory syndrome virus (PRRSV). Methods Blood samples were collected from the anterior vena cava of pigs after immunization, and blood indices, secreted levels of specific antibodies and neutralizing antibodies associated with humoral immunity, the proliferation capacity of T lymphocytes as a measure of cellular immunity, and secreted levels of IFN-γ and TNF-α were determined. Results The results showed that simultaneous immunization against CSFV and PRRSV infections induced strong and specific humoral and T-cellular immune responses, high levels of cytokine IFN-γ secretion and delayed secretion of cytokine TNF-α. Moreover, significantly higher lymphocyte percentages and red blood cell and leukocyte counts were found in the group simultaneously immunized against CSFV and PRRSV. However, no statistically significant differences were observed in hemoglobin values, neutrophil counts, and median cell percentages among the S + PRRS, PRRS-S, and S-PRRS groups. Conclusion This study demonstrated that simultaneous immunization against CSFV and PRRSV had the advantages of inducing a rapid, enhanced, and long-lasting immune response. These findings provide a theoretical basis for the establishment of a reasonable and optimized vaccine immunization protocol against CSFV and PRRSV in combination with a variety of other vaccine inoculations.

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FlagT4G Vaccine Prevents Transplacental Transmission of Highly Virulent Classical Swine Fever Virus after Single Vaccination in Pregnant Sows

Coronado,

Muñoz-Aguilera,

Cantero

et al. 2024

Vaccines

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The transplacental transmission of CSFV and the resulting persistent congenital infection in newborn piglets have been abundantly discussed in pregnant sows suffering from virus infection. Importantly, the availability of safe commercial vaccines with proven efficacy to prevent the generation of congenital and postnatal persistent infections in pregnant sows are critical tools for controlling the disease in CSF endemic areas. Here, we demonstrate the high efficacy of a single dose of the recombinant FlagT4G vaccine to provide solid protection in pregnant sows against transplacental transmission of a highly virulent CSFV. Pregnant sows vaccinated with FlagT4G at 44 days of gestation elicited a strong CSFV-specific antibody response, with neutralizing antibody levels above those required for protection against CSFV. Importantly, after the challenge with a highly virulent CSFV, all foetuses from FlagT4G-vaccinated sows lacked CSF macroscopic lesions and showed a complete absence of the challenge virus in their internal organs at day 79 of gestation. Therefore, pregnant sows safely vaccinated with FlagT4G without affecting reproductive efficacy are efficaciously protected, along with their foetuses, against the infection and disease caused by a CSFV virulent field strain.

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Removal of the E ^rns RNase Activity and of the 3′ Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease

Abstract: CSF is one of the most relevant viral epizootic diseases of swine, with high economic and sanitary impact. Systematic stamping out of infected herds with and without vaccination has permitted regional virus eradication.

Cited by 3 publications

References 48 publications

Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence

Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence

Optimized protocol for double vaccine immunization against classical swine fever and porcine reproductive and respiratory syndrome

FlagT4G Vaccine Prevents Transplacental Transmission of Highly Virulent Classical Swine Fever Virus after Single Vaccination in Pregnant Sows

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Removal of the E rns RNase Activity and of the 3′ Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease

Abstract: CSF is one of the most relevant viral epizootic diseases of swine, with high economic and sanitary impact. Systematic stamping out of infected herds with and without vaccination has permitted regional virus eradication.

Cited by 3 publications

References 48 publications

Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence

Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence

Optimized protocol for double vaccine immunization against classical swine fever and porcine reproductive and respiratory syndrome

FlagT4G Vaccine Prevents Transplacental Transmission of Highly Virulent Classical Swine Fever Virus after Single Vaccination in Pregnant Sows

Contact Info

Product

Resources

About

Removal of the E ^rns RNase Activity and of the 3′ Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease