[Comparative study of genomes of present-day influenza A and B viruses]. / Sravnitel'noe izuchenie genomov sovremennykh virusov grippa A i B.

The electrophoretic mobility of RNA fragments was used to study epidemic influenza viruses A and B as compared with the reference strains and virological findings. Among those tested, there was a further drift involving both the genes coding glycosylated proteins and internal and non-structural proteins. The analysis of atypical isolates showed their reassortant nature.

[The origin of resistance to chemicals of naturally occurring isolates of influenza A virus]. / Proiskhozhdenie rezistentnosti k khimiopreparatam u prirodnykh izoliatov virusa grippa A.

The mechanisms responsible for the formation of resistance of influenza A virus isolates during the natural circulation of the influenza viruses in the environment were studied. The influenza viruses H1N1 and H3N2 resistant to remantadine, adapromine, and deitiforine have been isolated in the USSR and Mongolia since 1982. The majority of natural resistant isolates appeared to be atypical both in antigenic properties and genomic structure as compared to the isolates prevalent in the common epidemic process. The nucleotide sequences of the M2 gene of some resistant strains and virus A/PR8/34 used in our country as an attenuation donor for preparation of killed recombinant vaccines. The electrophoretic mobility of genomic RNA of two resistant isolates is similar to that of the vaccine strain X-54 based on the virus A/PR/8/34. In this connection, the appearance of resistant strains in the environment may be due not only to spontaneous mutagenesis or selective drug actions, but also to the involvement into the circulation of vaccinal strains.

[Features of interepidemic influenza A and B viruses]. / Osobennosti mezhépidemicheskikh virusov grippa A i B.

The comparison of interepidemic influenza viruses with the pathogens of resultant influenza epidemics has revealed that they belong to the same type (subtype) of influenza virus. A definite correlation has been found between the antigenic specificity of haemagglutinin of epidemic and interepidemic strains. The antigenic structure of the interepidemic viruses and the pathogens of further epidemics of influenza B viruses have been found to be completely identical. The interepidemic A(H1N1) isolates have been shown to be antigenic analogues of the causative agents of influenza A(H1N1) during the previous epidemics. Despite the time and place of their isolation, as well as the etiology of the previous and subsequent epidemics, the interepidemic influenza A(H3N2) viruses have been ascertained to be similar to the reference A/Bangkok/1/79.

[Genetic predisposition to latent influenza A virus in children with blood type B(III) as a possible cause of new epidemiologic strains in the countries of South-Eastern Asia]. / Geneticheskaia predraspolozhennost detei s gruppoi krovi B(III) k latentnomu nositelstvu virusov grippa A - vozmozhnaia prichina vozniknoveniia novykh épidemicheskikh shtammov v stranakh Iugo- Vostochnoi Azii.

Regular clinical and epidemiological surveys of two groups of healthy 14-16-year-old boys were carried out for 3 years from September 1989 to May 1992 to investigate the latent circulation of influenza A viruses in the human population. Once or twice a quarter clinical materials were laboratorily studied to detect virus antigens, virus-specific NA-sequences and to determine changes in humoral immunity. The latent circulation of influenza A viruses might be identified in 10-20% of cases long before (2-4 months) the onset of epidemic development. The incidence of epidemic isolations was found to reach 33-36%, gradually decreasing from 29 to 9 or 3.5% in the postepidemic period. The long-term persistence (for 5 months) of virus antigens was reported among healthy children who had chiefly blood group B(III). The new hypothesis that the genetic predisposition of children with blood group B(III) to latent persistence of influenza A viruses may be a possible cause of the emergence of new epidemic strains in the South-East Asian countries has been forwarded.

[Influenza A virus antigens in children with congenital pathology of central nervous system]. / Nositelstvo antigenov virusa grippa A u detei s vrozhdennoi patologiei tsentralnoi nervnoi sistemy.

The latent circulation of influenza A virus in nursing home children with congenital central nervous abnormality was studied during 1989-1993 by the present-day diagnostic methods for detection of viral antigens. The influenza A virus antigen detection rates correlated with age, genetic predisposition, prior acute respiratory diseases in mothers during their pregnancy. There is evidence for long-term (up to 17 months) detection of influenza virus antigens in nasal secretions, as well as for prolonged (up to 7 months) detection of the same genomic sequences of HA gene both in leukocytes and nasal washes.

[Long-term carriers of genomic structures of the influenza virus in the blood leukocytes of children with congenital pathology of central nervous system]. / Dlitelnoe nositelstvo genomnykh struktur virusa grippa v leikotsitakh krovi detei s vrozhdennoi patologiei tsentralnoi nervnoi sistemy.

Children with central nervous abnormality were followed up for a long time (180 days). The clinical samples (nasal swabs, blood samples) were investigated for influenza virus antigens or RNA detection by virologic and molecular biological techniques. No viral isolate was found throughout the follow-up. The use of the polymerase chain reaction made it possible to reveal the long-term persistence (for 180 days) of NS- and genes of influenza A (H1N1) viruses in the leukocytes and of HA-gene in the nasal swabs. No NS-gene was found in the nasal swabs. The polymerase chain reaction appears to be more effective for the diagnosis of persistent influenza infection that the conventional techniques--immunofluorescence and enzyme-linked immunosorbent assay (ELISA).

[Influenza: current status and epidemiologic situation]. / Gripp: sostoianie problemy i tekushchaia épidemiologicheskaia situatsiia.

In the period of 1993 to 1994, influenza activity caused by circulation of viruses antigenically structurally related to the strain A/Beijing/32/92 (H3N2) began in the countries of North America and West Europe in October-November 1993, by spreading to the countries of East Europe, the Urals, and West Siberia. Epidemic events in China and in the Far East were evoked mainly by the influenza B virus. The influenza A (H1N1) viruses did not widely spread. Single isolates (about 1% of all the influenza A virus isolates, as evidenced by the CDC, Atlanta, USA) of this subtype were etiological agents of sporadic morbidity. A fourteen-year period (1977-1991) of the epidemic activity of the influenza A (H1N1) virus seems to be over. The last epidemic of the influenza A (H3N2) virus has a moderate intensity. Among all the age-group populations, children were largely afflicted. The highest incidence in Russia was recorded in Arkhangelsk, Barnaul, Nizhny Novgorod, Omsk, Samara, and Smolensk where approximately 16-18% of children under 14 years of age and 3.5-5% of the population of 15 years or more fell ill. The highest incidence was recorded in Minsk and Vilnus too.

[Polymorphism of current human influenza A and B virus population]. / Polimorfizm populiatsii sovremennykh virusov grippa A i B cheloveka.

During the past years, the etiological situation has been significantly complicated. It is characterized by simultaneous circulation of A(H1N1), A(H3N2) and influenza B viruses and by the isolation of reassortant strains and viruses, which are atypical in relation to the process of their natural variability. The antigenic properties of epidemic strains and unusual isolates were investigated. The marked heterogeneity of the A(H3N2) influenza viruses was demonstrated. It was determined by the circulation of several antigenic variants during the epidemic. Two separate antigenic lineage of the influenza B viruses--b/Victoria/2/87 and B/Yamagata/16/88--cocirculated in our country in 1991. Since 1986, all the influenza A(H1N1) viruses have been considered to be varieties of the reference strain A/Taiwan/1/86. A direct correlation was found between some atypical viruses and the vaccine strains previously used.

[The determination of the genotype of natural reassortant influenza A viruses according to the core protein genes by the methods of competitive dot hybridization and sequencing]. / Opredelenie genotipa prirodnykh reassortantov virusa grippa A po genam vnutrennikh belkov s pomoshch'iu metodov konkurentnoi tochechnoi gibridizatsii i sekvenirovaniia.

Simultaneous circulation of different subtypes of influenza A viruses provides conditions for reassortant strains formation. A comparative investigation of genome of 47 influenza A virus strains (H1N1, H2N2, and H3N2) was carried out by competitive dot hybridization technique and sequence analysis of some of cDNA-copies of the virus genes. All the genes of 43 strains encoding nonglycolysed proteins corresponded to the serum subtype of surface glycoproteins. The reassortant pattern of genome for some genes of core proteins was revealed in 4 viruses. All the dot hybridization data were completely confirmed by sequence analysis of the genes.

[Primary structure of the hemagglutinin gene in strains of the influenza virus A/Leningrad/624/86 and A/Leningrad/621/86 serologic subtype H1N1]. / Pervichnaia struktura gena gemaggliutinina shtammov virusa grippa A/Leningrad/624/86 i A/Leningrad/621/86 seropodtipa H1N1.

A molecular analysis was made of genomes of influenza A (H1N1) virus strains, the causative agents of an epidemic in Leningrad, 1986. The primary structure of hemagglutinin gene of two of these strains, A/Leningrad/624/86 and A/Leningrad/621/86, was established, as well as partial primary structure of PB1 gene of certain current strains of the A (H1N1) subtype. A hypothesis of a "shift" of PB1 gene in 1950-1957 is suggested.

[The primary structure of the hemagglutinin gene of strain A/Riga/9977/86--a drift variant of influenza virus A(H3N2)]. / Pervichnaia struktura gena gemaggliutinina shtamma A/Riga/9977/86--dreifovogo varianta virusa grippa A(H3N2).

The hemagglutinin gene primary structure of influenza virus A/Riga/9977/86 (H3N2) belonging to the "Coen/84" antigenic subgroup was determined by primer sequencing. A comparative analysis confirmed that the reversions of amino acids in the late stages of the H3 influenza virus subtype antigenic drift became more frequent and the antigenic variants remained in epidemic circulation longer. The possible role of some mutations is discussed.

[The isolation and study of the properties of current influenza A viruses (H1N1) with a natural resistance to remantadine]. / Vydelenie i izuchenie svoistv sovremennykh virusov grippa A (H1N1) s prirodnoi rezistentnost'iu k remantadinu.

Studies of influenza A viruses (H1N1) isolated in 1985-1988 revealed 4 strains with natural resistance to chemical drugs (remantadine, adapromine, deitiforin). Three of them were isolated in Mongolia (A/Mongolia/230/85, A/Mongolia/231/85, and A/Mongolia/128/86) and one in the USSR (A/Moscow/771/88). These strains differed from other isolates by the following features: (i) antigenic remoteness from reference A/Chile/1/83 and A/Taiwan/1/86; (ii) similarity in antigenic specificity with A/Khabarovsk/74/77; (iii) resistance to chemical drugs; (iv) high electrophoretic mobility of genes M and NS in PAG. The possible origin of these strains is discussed.

Primary structure of the gene coding for the haemagglutinin of influenza virus A/Leningrad/385/80(H3N2): detection of a point mutation responsible for the antigenic drift.

Primary structure of the gene coding for haemagglutinin (HA-gene) of influenza virus A/Leningrad/385/80(H2N2) isolated during the epidemics of influenza in Leningrad in 1980 was determined. The close relationship of HA gene of this virus to the corresponding gene of the virus A/Bangkok/1/79(H3N2) was confirmed. It was shown that a single mutation in an antigenic site (the change from isoleucine to leucine at position 51 of HA1 gene) caused an antigenic drift. One silent mutation was detected (nucleotide 428 of HA1 gene) which points at the relatedness of strains A/Leningrad/385/80 with A/Bangkok/2/79 and with other more recent strains. These data allowed to determine the position of the strain A/Leningrad/385/80 HA gene regarding to the evolutionary relationships of HA genes of influenza A (H3N2 subtype) viruses. The branch leading to the above-mentioned strain is supposed to start from a point common for strains isolated following A/Bangkok/1/79. The mutations of HA genes presented in this subgroup were analysed supporting the notion on limited evolutionary potential of the subtype H3N2 influenza viruses.

[Characteristics of the influenza type A (H3N2) epidemic in Omsk in January 1985]. / Kharakteristika épidemii grippa tipa A (H3N2) v Omske v ianvare 1985 g.

The work presents the data obtained in analysis of the epidemic situation among the population of Omsk in January-February 1985 and the characterization of the isolated strains of influenza A (H3N2) virus, determines the specific features of the course of the influenza epidemic process among different social and age groups, evaluates anti-influenza measures.

Laboratory characterization of influenza A viruses (H3N2)--pathogens of Leningrad 1983 epidemic.

Seventy strains of influenza A virus (H3N2) isolated in Leningrad during the influenza epidemic in January--March 1983 were studied. The virus isolates appeared to be markedly heterogeneous with respect to antigenic characteristics of surface glycoproteins, biological properties (haemagglutinating and neuraminidase activities, sensitivity to gamma-inhibitors, etc.) as well as genome structure. The identity of the virus isolates with the reference influenza A virus was as follows: 10% were similar to A/Texas/1/77 virus, 30% to A/Bangkok/1/79 virus, and 20% to A/Philippines/2/82 virus. A large part of the isolated viruses (27 of 70) were characterized by a certain (mainly unilateral) relatedness with the virus A/Victoria/35/72. The isolates were extremely heterogeneous with respect to genomic characteristics as determined by cRNA-vRNA hybridization test and differed from the corresponding reference strains by the homology of genes 1-6.

[Genomic and antigenic analysis of strains of influenza A virus (H1N1) isolated in 1982-1983: approaches to the choice of the optimal vaccine strain]. / Genomnyi i antigennyi analiz shtammov virusa grippa A (H1N1) 1982-1983 gg. vydeleniia: podkhody k vyboru optimal'nogo vaktsinnogo shtamma.

Features of the genome and antigenic specificity of hemagglutinin of some influenza A (H1N1) virus strains circulating in the epidemic period of 1982-1983 were studied comparatively. Analysis of the genome of the isolates under study in comparison with that of the reference A/England/333/80 strain and with each other has established changes not only in the genes coding for hemagglutinin and neuraminidase but also most of the genes coding for unglycolysed proteins. The antigenic specificity of hemagglutinin of the isolates under study examined with rat antisera and monoclonal antibodies was found to be quite dissimilar. Hemagglutinin of the A/Dunedin/27/83 strain induced antibodies capable of reacting predominantly with the homologous strain whereas antibodies to hemagglutinin of the A/Leningrad/16/16/82 and A/Chile/1/83 strains had a wide spectrum of antigenic specificity and neutralized well the hemagglutinin of different variants of influenza virus of H1N1 serotype circulating at that time. Among the 1982-1983 isolates studied, the A/Leningrad/16/16/82 strain was selected which, by its hemagglutinin properties, is optimal for preparation of inactivated vaccine, as was confirmed by the study of an experimental batch of such vaccine in volunteers.