Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence
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Author
Hinojosa, Yoandry
Liniger, Matthias
García-Nicolás, Obdulio
Gerber, Markus
Rajaratnam, Anojen
Muñoz-González, Sara
Frías, María Teresa
Perera, Carmen Laura
Ruggli, Nicolas
Publication date
2024-01-19ISSN
1999-4915
Abstract
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 monocytederived 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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
20
Publisher
MDPI
Is part of
Viruses
Citation
Hinojosa, Yoandry, Matthias Liniger, Obdulio García-Nicolás, Marlène Gerber, Anojen Rajaratnam, Sara Muñoz-González, Liani Coronado, et al. 2024. “Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence.” Viruses 16 (1): 147. doi: 10.3390/v16010147.
Program
Sanitat Animal
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