Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar

Muñoz-González, Sara; Pérez‐Simó, Marta; Colom-Cadena, Andreu; Cabezón, Óscar; Bohórquez, José Alejandro; Rosell, Rosa; Pérez, Lester J.; Marco, Ignasi; Lavı́n, Santiago; Domingo, Mariano; Ganges, Llilianne

doi:10.1371/journal.pone.0149469

Cited by 21 publications

(25 citation statements)

References 60 publications

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“…However, when the virus is introduced through natural routes, the influencing factors could be more numerous and much complicated. To further explore the natural situations and to evaluate the possible effect of the superinfection exclusion phenomenon of CSFV [27] in the field in terms of the competence of these two genotypes, cohabitation infection with 2.1 virus infected pigs and 3.4 virus infected pigs is warranted.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Demonstration of the Superior Replication and Infectivity of Genotype 2.1 with Respect to Genotype 3.4 of Classical Swine Fever Virus by Dual Infections

et al. 2020

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In Taiwan, the prevalent CSFV population has shifted from the historical genotype 3.4 (94.4 strain) to the newly invading genotype 2.1 (TD/96 strain) since 1996. This study analyzed the competition between these two virus genotypes in dual infection pigs with equal and different virus populations and with maternally derived neutralizing antibodies induced by a third genotype of modified live vaccine (MLV), to simulate that occurring in natural situations in the field. Experimentally, under various dual infection conditions, with or without the presence of maternal antibodies, with various specimens from blood, oral and fecal swabs, and internal organs at various time points, the TD/96 had consistently 1.51−3.08 log higher loads than those of 94.4. A second passage of competition in the same animals further widened the lead of TD/96 as indicated by viral loads. The maternally derived antibodies provided partial protection to both wild type CSFVs and was correlated with lower clinical scores, febrile reaction, and animal mortality. In the presence of maternal antibodies, pigs could be infected by both wild type CSFVs, with TD/96 dominating. These findings partially explain the CSFV shift observed, furthering our understanding of CSFV pathogenesis in the field, and are helpful for the control of CSF.

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Section: Discussionmentioning

confidence: 99%

In Vivo Demonstration of the Superior Replication and Infectivity of Genotype 2.1 with Respect to Genotype 3.4 of Classical Swine Fever Virus by Dual Infections

et al. 2020

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“…Consequently, considering the low CD4/CD8 ratio and the reduced impact of the cytokine storm phenomenon, at least in terms of IFN-α, evidenced in CSFV persistently infected animals after super-infection with CSFV or African swine fever virus (Cabezón et al, 2017;Muñoz-González et al, 2016); we suggest the possible implication of the immune exhaustion mechanism that may favour the constant and high CSFV replication levels during CSFV persistence (Cabezón et al, 2017;Muñoz-González et al, 2016). Nevertheless, further studies will be performed to clarify the role of the immune exhaustion phenomenon and other immunosuppressive disorders in the CSFV pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Low CD4/CD8 ratio in classical swine fever postnatal persistent infection generated at 3 weeks after birth

Bohórquez

Wang

Pérez‐Simó

et al. 2018

Transbound Emerg Dis

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Classical swine fever virus (CSFV) is one of the most important pathogens affecting swine. After infection with a moderate virulence strain at 8 hours after birth, CSFV is able to induce viral persistence. These animals may appear clinically healthy or showed unspecific clinical signs despite the permanent viremia and high viral shedding, in absence of immune response to the virus. Given the role played by this infection in disease control, we aimed to evaluate the capacity of CSFV to induce postnatal persistent infection at 3 weeks after birth. Nine pigs were CSFV infected and sampled weekly during 6 weeks and viral, clinical, pathological and immunological tests were carried out. Also, the CD4/CD8 ratio was calculated with the purpose to relate this marker with the CSFV persistent infection. The IFN‐α response was detected mainly 1 week after infection, being similar in all the infected animals. However, 44.4% of animals were CSFV persistently infected, 33.3% died and 22.2% developed specific antibody response. Interestingly, in persistently infected pigs, the T‐CD8 population was increased, the T‐CD4 subset was decreased and lower CD4/CD8 ratios were detected. This is the first report of CSFV capacity to confer postnatal persistent infection in pigs infected at 3 weeks after birth, an age in which the weaning could be carried out in some swine production systems. This type of infected animals shed high amounts of virus and are difficult to evaluate from the clinical and anatomopathological point of view. Therefore, the detection of this type of infection and its elimination in endemic areas will be relevant for global CSF eradication. Finally, the low CD4/CD8 ratios found in persistently infected animals may be implicated in maintaining high CSFV replication during persistence and further studies will be performed to decipher the role of these cells in CSFV immunopathogenesis.

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“…The high stability showed by this low virulent CSFV field strain may be linked to a potential adaptive advantage, which may favour the prevalence of the low virulent strain circulating in the field. Considering the role of the mechanism showing the suppression of superinfection (SIE) in CSFV persistently infected pigs, the possible outcome of the generation of the new low pathogenicity CSFV strains circulating in an endemic situation and the impact of the SIE on disease control cannot be underrated (Muñoz-González et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Novel poly-uridine insertion in the 3′UTR and E2 amino acid substitutions in a low virulent classical swine fever virus

Coronado

Liniger²,

Muñoz-González

et al. 2017

Veterinary Microbiology

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In this study, we compared the virulence in weaner pigs of the Pinar del Rio isolate and the virulent Margarita strain. The latter caused the Cuban classical swine fever (CSF) outbreak of 1993. Our results showed that the Pinar del Rio virus isolated during an endemic phase is clearly of low virulence. We analysed the complete nucleotide sequence of the Pinar del Rio virus isolated after persistence in newborn piglets, as well as the genome sequence of the inoculum. The consensus genome sequence of the Pinar del Rio virus remained completely unchanged after 28days of persistent infection in swine. More importantly, a unique poly-uridine tract was discovered in the 3'UTR of the Pinar del Rio virus, which was not found in the Margarita virus or any other known CSFV sequences. Based on RNA secondary structure prediction, the poly-uridine tract results in a long single-stranded intervening sequence (SS) between the stem-loops I and II of the 3'UTR, without major changes in the stem- loop structures when compared to the Margarita virus. The possible implications of this novel insertion on persistence and attenuation remain to be investigated. In addition, comparison of the amino acid sequence of the viral proteins E, E1, E2 and p7 of the Margarita and Pinar del Rio viruses showed that all non-conservative amino acid substitutions acquired by the Pinar del Rio isolate clustered in E2, with two of them being located within the B/C domain. Immunisation and cross-neutralisation experiments in pigs and rabbits suggest differences between these two viruses, which may be attributable to the amino acid differences observed in E2. Altogether, these data provide fresh insights into viral molecular features which might be associated with the attenuation and adaptation of CSFV for persistence in the field.

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Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar

Cited by 21 publications

References 60 publications

In Vivo Demonstration of the Superior Replication and Infectivity of Genotype 2.1 with Respect to Genotype 3.4 of Classical Swine Fever Virus by Dual Infections

In Vivo Demonstration of the Superior Replication and Infectivity of Genotype 2.1 with Respect to Genotype 3.4 of Classical Swine Fever Virus by Dual Infections

Low CD4/CD8 ratio in classical swine fever postnatal persistent infection generated at 3 weeks after birth

Novel poly-uridine insertion in the 3′UTR and E2 amino acid substitutions in a low virulent classical swine fever virus

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