Recombinants between attenuated and virulent strains of poliovirus type 1: Derivation and characterization of recombinants with centrally located crossover points

Agol, Vadim I.; Drozdov, S. G.; Grachev, V. T.; Kolesnikova, Marina S.; Kozlov, V.G.; Ralph, N. M.; Romanova, Lyudmila I.; Tolskaya, Elena A.; Tyufanov, A. V.; Viktorova, Ekaterina G.

doi:10.1016/0042-6822(85)90386-1

Cited by 39 publications

(17 citation statements)

References 16 publications

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“…The contribution of the 3′ half of the genome to the pathogenicity of PVs was demonstrated in previous studies25265455, but the precise underlying mechanisms remain to be deciphered. These mechanisms may involve different pathways, including, in particular, the replication machinery, which mobilizes proteins encoded by the non-structural regions of the genome and three-dimensional RNA structures within the 3′UTR56.…”

Section: Discussionmentioning

confidence: 92%

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

Bessaud

Joffret

Blondel

et al. 2016

Sci Rep

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The attenuated Sabin strains contained in the oral poliomyelitis vaccine are genetically unstable, and their circulation in poorly immunized populations can lead to the emergence of pathogenic circulating vaccine-derived polioviruses (cVDPVs). The recombinant nature of most cVDPV genomes and the preferential presence of genomic sequences from certain cocirculating non-polio enteroviruses of species C (EV-Cs) raise questions about the permissiveness of genetic exchanges between EV-Cs and the phenotypic impact of such exchanges. We investigated whether functional constraints limited genetic exchanges between Sabin strains and other EV-Cs. We bypassed the natural recombination events by constructing 29 genomes containing a Sabin 2 capsid-encoding sequence and other sequences from Sabin 2 or from non-polio EV-Cs. Most genomes were functional. All recombinant viruses replicated similarly in vitro, but recombination modulated plaque size and temperature sensitivity. All viruses with a 5′UTR from Sabin 2 were attenuated in mice, whereas almost all viruses with a non-polio 5′UTR caused disease. These data highlight the striking conservation of functional compatibility between different genetic domains of cocirculating EV-Cs. This aspect is only one of the requirements for the generation of recombinant cVDPVs in natural conditions, but it may facilitate the generation of viable intertypic recombinants with diverse phenotypic features, including pathogenicity.

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Section: Discussionmentioning

confidence: 92%

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

Bessaud

Joffret

Blondel

et al. 2016

Sci Rep

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“…The high frequency of recombination also made possible the isolation of different recombinant viruses with minor variations in their crossover sites. The availability of these recombinants allowed for a fine genetic mapping of coronaviral functions, such as monoclonal antibody binding sites, which had not been achieved with recombinants (26,27) or reassortants (28) of other RNA viruses. Thus, RNA recombination of coronavirus provides a particularly powerful genetic tool.…”

Section: Discussionmentioning

confidence: 99%

RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers.

Makino¹,

Fleming²,

Keck³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Murine coronaviruses undergo RNA recombination at a very high frequency. We have obtained a series of recombinant viruses using neutralizing monoclonal antibodies in conjunction with temperature-sensitive markers. All of the recombinants obtained have a crossover within gene C, which encodes the peplomer protein of the virus. The genetic structure of these recombinants suggests that the antigenic regions recognized by these neutralizing monoclonal antibodies are localized on the carboxyl-terminal one-third of the peplomer protein. Since the two monoclonal antibodies used are also associated with the critical determinants of virus neuropathogenicity, we conclude that both the neutralizing antibody binding sites and determinants of pathogenicity are localized at the carboxyl-terminal one-third of the peplomer. The variation of crossover sites in different recombinant viruses also allowed precise mapping of additional antigenic sites. RNA recombination thus presents a powerful genetic tool, and the carboxylterminal localization of the biological functions of peplomers suggests a distinct conformation of these viral membrane proteins.Mouse hepatitis virus (MHV), a coronavirus, is an enveloped virus containing two envelope glycoproteins, El and E2, and a nucleocapsid protein, N (1). The N protein has a molecular weight of 60,000 and is closely associated with viral RNA. The El glycoprotein has a molecular weight of -25,000 and probably serves as a matrix protein. The E2 glycoprotein, a 180-kDa heterodimer, forms the projecting spikes or peplomers on the surface of the virus particle and is involved in the attachment of virus to target cells, in the induction of cell-to-cell fusion, and in the elicitation of neutralizing antibodies (1-3). Competitive binding studies have identified at least six major antigenic sites on the E2, three of which are involved in virus neutralization (refs. 4 MHV contains a single piece of single-stranded RNA genome of positive polarity (9). The RNA contains at least seven genes, termed genes A through G in the 5'-3' order, based on the finding that, in infected cells, six subgenomic and one genomic mRNAs are expressed (10). These mRNAs have a 3'-coterminal, nested-set structure, i.e., the sequence of each mRNA is contained entirely within the next larger mRNA (10). Only the 5'-specific portions, which do not overlap with the next smaller mRNAs, are translated. Furthermore, each mRNA contains a leader sequence of '70 nucleotides, which is derived from the 5' end of the genome and joined to the mRNAs by a mechanism of "leader-primed transcription" (11,12). Despite the fact that MHV genome is a single, nonsegmented RNA, our laboratory has demonstrated that MHV can undergo RNA-RNA recombination at an extremely high frequency (13), reminiscent of the genetic reassortment of viruses with segmented RNA genomes. This observation suggests that fragmented RNA intermediates might be generated during replication of MHV RNA, probably by a mechanism of discontinuous and nonprocessive RNA synth...

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“…Oligonucleotide fingerprinting was the next method used to study recombination in poliovirus [15,16]. In the pre-reverse genetics era, poliovirus recombinants were the only tool available to map neurovirulence determinants [17][18][19]. Recombination in poliovirus was also achieved in a cell-free system [20,21].…”

Section: Recombination In Poliovirusmentioning

confidence: 99%

Role of recombination in evolution of enteroviruses

2005

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Enteroviruses, members of the Picornaviridae family, comprise a large (over 70 serotypes) group of viruses that are ubiquitous in nature, infect different species and cause a wide range of diseases. Human enteroviruses were recently classified into five species, human enterovirus A-D and poliovirus. Recombination has long been known to be an important property of poliovirus genetics. Recently, several publications demonstrated that recombination is extremely frequent also in non-polio enteroviruses, and allows independent evolution of enterovirus genome fragments even on a microevolutionary scale. Prototype enterovirus strains were shown to have complex phylogenetic relations, and almost all modern enterovirus isolates turned out to be recombinants compared with the prototype strains. Recombination takes place strictly between members of the same species, and usually spares the capsid-encoding genome region. Therefore, it can be concluded that the enterovirus species exist as a worldwide reservoir of genetic material comprising a limited quantity of capsid gene sets defining a finite number of serotypes and a range of non-structural genes that recombine frequently to produce new virus variants. This new model of enterovirus genetics helps to explain the failure of previous attempts to connect serotype and disease profile in non-polio enteroviruses, and seriously questions existing typing approaches that are based solely on the capsid-encoding genome region. It remains to be determined what role recombination plays in the emergence of new enterovirus variants and in the macroevolution of animal enteroviruses and viruses of the picorna-like supergroup.

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Recombinants between attenuated and virulent strains of poliovirus type 1: Derivation and characterization of recombinants with centrally located crossover points

Cited by 39 publications

References 16 publications

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers.

Role of recombination in evolution of enteroviruses

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