Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine

Westrop, Gareth D.; Wareham, K A; Evans, D. M. A.; Dunn, Glynis; Minor, Philip D.; Magrath, D. I.; Taffs, F.; Marsden, S.A.; Skinner, Michael A.; Schild, G. C.

doi:10.1128/jvi.63.3.1338-1344.1989

Cited by 222 publications

(96 citation statements)

References 26 publications

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“…This heterogenicity of the PRRSV 5 -end sequence should be further investigated for its relevance. Interestingly, both ends of viral sequences have been shown to not only play an important role in the replication of coronaviruses, another member of the order Nidovirales (Williams et al, 1999), but they are also related to poliovirus attenuation (Westrop et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of PL97-1, the first Korean isolate of the porcine reproductive and respiratory syndrome virus

et al. 2004

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We determined the complete nucleotide and predicted amino acid sequence of the genomic RNA of PL97-1, the first Korean strain of porcine reproductive and respiratory syndrome virus (PRRSV), which was isolated from the serum of an infected pig in 1997. We found that the 15411-nucleotide genome of PL97-1 consisted of a 189-nucleotide 5' noncoding region (NCR), a 15071-nucleotide protein-coding region, and a 151-nucleotide 3'NCR, followed by a poly (A) tail. The 5'-end of PL97-1 began with 1ATG ACG TAT AGG12. Comparison of the PL97-1 genome with the 11 fully sequenced PRRSV genomes currently available revealed sequence divergence ranging from 0.3% (the VR-2332-derived vaccine MLV RespPRRS/Repro strain) to 38% (the Dutch Lelystad strain). To better understand the genetic relationships between these different strains, phylogenetic analyses were performed on the full-length PRRSV genomes. Significantly, the phylogenetic tree based on the ORF1b or ORF7 genes most closely resembled the tree based on the full-length genomes. Thus, these single genes will be the most useful in revealing the genetic relationships between the different strains relative to their geographical distribution. Extensive phylogenetic analyses using the ORF7 sequences of 111 PRRSV isolates available revealed that PL97-1 is most closely related to the North American genotype VR-2332, a VR-2332-derived vaccine strain, and Chinese BJ-4. It is distantly related to the European genotype Lelystad. This study provides the largest full-length genome phylogenetic analysis of PRRSV that has been published to date, and supports an earlier genetic grouping of the many temporally and geographically diverse PRRSV strains currently isolated.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of PL97-1, the first Korean isolate of the porcine reproductive and respiratory syndrome virus

et al. 2004

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“…In the guts of vaccinees, such reversions occur very often and quite rapidly at positions 480, 481, and 472 in the RNAs of OPV serotypes 1, 2, and 3, respectively (307-311; reviewed in references 312 to 314), leading to restoration of their somewhat impaired secondary (for serotypes 1 and 3) or tertiary (for serotype 2) structures (104, 311, 315) ( Fig. 4) and, consequently, translational activity (316)(317)(318)(319) and neurovirulence (308,315,320,321).…”

Section: Rehabilitation After Adverse Changes In the Untranslated Regmentioning

confidence: 99%

“…The Sabin OPV strains contain attenuation mutations not only in their IRES elements but also in the encoded proteins (321,(344)(345)(346)(347). Some of them are known to readily revert in vaccinees or during subsequent transmission, resulting in the restoration of viral fitness (reviewed in references 312 and 313).…”

Section: Rehabilitation After Adverse Changes In Viral Proteinsmentioning

confidence: 99%

Emergency Services of Viral RNAs: Repair and Remodeling

Agol

Gmyl

2018

Microbiol Mol Biol Rev

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Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.

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“…However, one or more of these silent mutations could change the secondary or tertiary structure of PRRSV RNA and thus alter the stability of the genome. In other viruses, such as picornaviruses, viral RNA folding may play a critical role in host protein association (Meerovitch et al, 1989) and in neurovirulence (Pilipenko et al, 1989a,b;Westrop et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…The 5% and 3% ends of viral sequences have been correlated with attenuation in other viruses, such as poliovirus (Westrop et al, 1989), and shown to be important in viral replication and transcription for coronaviruses, another member of the Nidovirus order (Williams et al, 1999). Only two mutations occurred in the 5%-end of PRRSV during attenuation of strain VR-2332 to RespPRRS, and their relative roles in attenuation must be further investigated.…”

Section: Discussionmentioning

confidence: 99%