Biomedical subjects

S G Drozdov

Publications and source records attributed to S G Drozdov.

At least 37 records · Page 2Linked to original sources

PubMed1985

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

Recombinants with a centrally located crossover point were selected from crosses between poliovirus type 1 strains and intertypic (type 3/type 1) recombinants. Two such recombinants were characterized in some detail. In one of them (v1/a1-6), the 5' half of the genome was derived from a virulent type 1 strain, while the 3' half came from an attenuated type 1 strain. The genome of the other recombinant (a1/v1-7) had the reverse organization, with the 5' and 3' halves being derived from the type 1 attenuated and virulent strains, respectively. As deduced from the RNase T1 oligonucleotide maps, the a1/v1-7 genome also had a relatively short centrally located insert of the poliovirus type 3 origin. Both recombinants exhibited ts phenotypes. The RNA phenotypes of the recombinants corresponded to that of the parent donating the 3' half of the genome, v1/a1-6 and a1/v1-7 expressing RNA- and RNA +/- characters, respectively. Despite being a ts RNA- virus, v1/a1-6 proved to be neurovirulent when injected intracerebrally into Cercopithecus aethiops monkeys, although it exhibited a somewhat diminished level of pathogenicity as compared to its virulent type 1 parent. Recombinant a1/v1-7 behaved as an attenuated strain. These data supported our previous conclusion drawn from the experiments with intertypic poliovirus recombinants that the attenuated phenotype of poliovirus depends largely on the structure of the 5' half of its genome, although mutations of the 3' half may alleviate the virulence of the virus to a degree.

Base Sequence↗

PubMed1985

Neurovirulence of the intertypic poliovirus recombinant v3/a1-25: characterization of strains isolated from the spinal cord of diseased monkeys and evaluation of the contribution of the 3' half of the genome.

A tsRNA- intertypic recombinant, v3/a1-25, which has the 5' and 3' halves of the genome derived from the neurovirulent type 3 poliovirus strain 452/62 3D and the attenuated type 1 poliovirus strain LSc-gr3, respectively, was previously shown to cause severe paralytic poliomyelitis after intracerebral inoculation of monkeys. To ascertain whether the illness was caused by the recombinant itself or by temperature-resistant trRNA+ mutants that might have arisen in the inoculated monkeys, five independent virus strains have been isolated from the spinal cord of the diseased animals. While two of these isolates exhibited RNA+ and RNA +/- phenotypes, respectively, the other three strains retained the parental RNA- character. Except for the RNA+ strain, the RNase T1 oligonucleotide maps of the genomes of all the isolates revealed only a minimal deviation from the parental pattern. These results were interpreted to mean that v3/a1-25 is intrinsically neurovirulent despite the presence of a tsRNA- mutation(s) in the 3' half of its genome. Nevertheless, this mutation, or other peculiarities of the 3' half of the recombinant genome, may somewhat alleviate the pathogenicity of the virus. This notion was inferred from the fact that, when used in a relatively small dose (about 10(3) p.f.u.), v3/a1-25 appeared to exhibit a lower level of neurovirulence compared to either the wild-type parent 452/62 3D, or a closely related intertypic recombinant having the genome 3' half derived from a neurovirulent trRNA +/- type 1 poliovirus strain. The problem of genetic determination of poliovirus neurovirulence and attenuation is briefly discussed.

Animals↗

PubMed1985

[Characteristics of the genome of poliovirus type 3 isolated from patients with poliomyelitis in Moldavia].

Twelve poliovirus isolates of serotype 3 from patients with paralytic poliomyelitis have been analyzed by oligonucleotide mapping of the viral genomes. All the studied strains were isolated from patients in different regions of the Moldavian SSR in 1982. The maps of all isolates are similar but they do not practically possess any large oligonucleotides characteristic of the vaccine strain of type 3 poliovirus. It is concluded that a wild neurovirulent strain of type 3 poliovirus, that circulated in 1982 in the Moldavian SSR was the cause of paralytic poliomyelitis cases. All the studied isolates are suggested to have been derived relatively recently from the common ancestor.

DNA, Viral↗

PubMed1984

Construction and properties of intertypic poliovirus recombinants: first approximation mapping of the major determinants of neurovirulence.

An attempt was made to map, in a general way, the region of the poliovirus genome that is responsible for the neurovirulent and attenuated phenotypes of different virus strains. A set of four recombinants was investigated, one described previously (E. A. Tolskaya, L. I. Romanova, M. S. Kolesnikova, and V. I. Agol, 1983, Virology 124, 121-132) and three obtained in the present work with the following genetic structure: a 5' end-adjacent segment of the genome derived from either a virulent strain (452/62 3D), or from an attenuated strain (Leon-2) of poliovirus type 3, the remaining RNA sequences being derived from either a virulent strain (Mgr), or an attenuated strain (LSc-gr3) of poliovirus type 1. The crossover points in the recombinant genomes were centrally located, somewhere between the gene(s) that determines antigenic specificity of the virus and the locus that determines resistance of virus multiplication to low doses of guanidine. The recombinant nature of the newly selected clones was definitively established by mapping RNase T1 oligonucleotides of their genome. The recombinants were characterized with respect to their ability to produce infectious progeny and synthesize viral RNA at an elevated temperature. Neurovirulence of the recombinants was assayed by intracerebral inoculation of monkeys. Irrespective of the origin of the 3' end-adjacent segment of the genome, the recombinants that inherited the 5' end-adjacent segment from the neurovirulent parent were neurovirulent, whereas the recombinants with the 5' end-adjacent segment derived from the attenuated parent were not. The results suggest that the major determinants of neurovirulence of these recombinants (and by inference, of their parental viruses) reside in the 5' end-adjacent segment of poliovirus genome, known to code for capsid proteins.

Animals↗

PubMed1984