ArticleJournal of virology2016
The Attenuation Phenotype of a Ribavirin-Resistant Porcine Reproductive and Respiratory Syndrome Virus Is Maintained during Sequential Passages in Pigs.
Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Single amino acid substitution in RdRp reduces viral recombination frequency of NADC30-like porcine reproductive and respiratory syndrome virus type 2.PLoS pathogens · 2026Article
- Self-assembled cyanidin-3-O-glucoside nanoparticles alleviate inflammation and ferroptosis induced by PRRSV infection.Journal of virology · 2025Article
- First study to describe the prevalence and epidemiology of African swine fever, classical swine fever, porcine reproductive and respiratory syndrome and swine flu in Kazakhstan.BMC veterinary research · 2025Article
- Contribution of critical amino acid residues in the RNA-dependent RNA polymerase to the replication fidelity and viral ribavirin sensitivity of porcine reproductive and respiratory syndrome virus.Veterinary research · 2025Article
- Hesperetin Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Downregulating the P38/JUN/FOS Pathway In Vitro.Microorganisms · 2025Article
- Antiviral effects and mechanism of Ma-Xing-Shi-Gan-San on porcine reproductive and respiratory syndrome virus.Frontiers in microbiology · 2025Article
- Alterations of SARS-CoV-2 Evolutionary Dynamics by Pharmaceutical Factors.Infectious diseases & immunity · 2024Review
- Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool.Frontiers in veterinary science · 2023Article
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- Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A "Leaky" Vaccine with Debatable Efficacy and Safety.Vaccines · 2021Review
- Curcumin as an Antiviral Agent.Viruses · 2020Review
- An E460D Substitution in the NS5 Protein of Tick-Borne Encephalitis Virus Confers Resistance to the Inhibitor Galidesivir (BCX4430) and Also Attenuates the Virus for Mice.Journal of virology · 2019Article
- Evaluation of the Inhibitory Effects of (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (DiNap), a Natural Product Analog, on the Replication of Type 2 PRRSV In Vitro and In Vivo.Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledIn a previous study, ribavirin-resistant porcine reproductive and respiratory syndrome virus (PRRSV) mutants (RVRp13 and RVRp22) were selected, and their resistance against random mutation was shown in cultured cells. In the present study, these ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability during three pig-to-pig passages in comparison with modified live virus (MLV) (Ingelvac PRRS MLV). Pigs challenged with RVRp22 had significantly lower (P< 0.05) viral loads in sera and tissues than pigs challenged with MLV or RVRp13 at the first passage, and the attenuated replication of RVRp22 was maintained until the third passage. Viral loads in sera and tissues dramatically increased in pigs challenged with MLV or RVRp13 during the second passage. Consistently, all five sequences associated with the attenuation of virulent PRRSV in RVRp13 and MLV quickly reverted to wild-type sequences during the passages, but two attenuation sequences were maintained in RVRp22 even after the third passage. In addition, RVRp22 showed a significantly lower (P< 0.001) mutation frequency in nsp2, which is one of the most variable regions in the PRRSV genome, than MLV. Nine unique mutations were found in open reading frames (ORFs) 1a, 2, and 6 in the RVRp22 genome based on full-length sequence comparisons with RVRp13, VR2332 (the parental virus of RVRp13 and RVRp22), and MLV. Based on these results, it was concluded that RVRp22 showed attenuated replication in pigs; further, because of the high genetic stability of RVRp22, its attenuated phenotype was stable even after three sequential passages in pigs. IMPORTANCE: PRRSV is a rapidly evolving RNA virus. MLV vaccines are widely used to control PRRS; however, there have been serious concerns regarding the use of MLV as a vaccine virus due to the rapid reversion to virulence during replication in pigs. As previously reported, ribavirin is an effective antiviral drug against many RNA viruses. Ribavirin-resistant mutants reemerged by escaping lethal mutagenesis when the treatment concentration was sublethal, and those mutants were genetically more stable than parental viruses. In a previous study, two ribavirin-resistant PRRSV mutants (RVRp13 and RVRp22) were selected, and their higher genetic stability was shown in vitro Consequently, in the present study, both of the ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability in vivo RVRp22 was found to exhibit higher genetic and phenotypic stability than MLV, and nine unique mutations were identified in the RVRp22 genome based on a full-length sequence comparison with the RVRp13, VR2332, and MLV genomes.
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