Phylodynamic characteristics of the Russian population of rotavirus А (Reoviridae: Sedoreovirinae: Rotavirus) based on the VP6 gene

Cover Page

Cite item


Introduction. Rotavirus A is one of the leading causes of acute gastroenteritis in children in the first years of life. Rotavirus infection is currently classified as a preventable infection. The most abundant rotavirion protein is VP6.

Material and methods. Phylogenetic analysis and calculation of phylodynamic characteristics were carried out for 262 nucleotide sequences of the VP6 gene of rotavirus species A, isolated in Russia, using the BEAST v.1.10.4 software package. The derivation and analysis of amino acid sequences was performed using the MEGAX program.

Results. This study provides phylodynamic characteristics of the rotaviruses in Russia based on the sequences coding VP6 protein. Bayesian analysis showed the circulation of rotaviruses of three sublineages of genotype I1 and three sublineages of genotype I2 in Russia. The level of accumulation of mutations was established, which turned out to be similar for genotypes I1 and I2 and amounted to 7.732E-4 and 1.008E-3 nucleotides/site/year, respectively. The effective population sizes based on nucleotide sequences of the VP6 I1 and I2 genotypes are relatively stable while after the 2000s there is a tendency of its decreasing. Comparative analysis of the amino acid sequences in the region of the intracellular neutralization sites A (231–260 aa) and B (265–292 aa) made it possible to reveal a mutation in position V252I in a proportion of Russian strains of genotype I1 some strains of genotypes I1 and I2 had mutation I281V. These substitutions were not associated with any sublineages to which the strains belong. The analysis of three T-cell epitopes revealed four amino acid differences (in aa positions 305, 315, 342, 348) that were associated with the first or second genogroup.

Conclusion. Based on the phylodynamic characteristics and amino acid composition of antigenic determinants, it was concluded that the VP6 protein is highly stable and could potentially be a good model for development of a rotavirus vaccine.

Full Text


Group A rotaviruses (the family Reoviridae, the subfamily Sedoreovirinae, the genus Rotavirus) are a major cause of acute gastroenteritis in infants in the first years of life [1]. Rotavirus A (RVA) is the etiologic agent of gastroenteritis in 43% hospitalization cases among children under 5 years in Russia. Among outpatient visits, rotavirus gastroenteritis accounts for 31%, reaching 75% in some regions of Russia [2]. In the Russian Federation, the rotavirus infection (RVI) has a winter and spring seasonal pattern [3]. Two rotavirus vaccines are currently used worldwide: the RV1 monovalent, human, oral, live attenuated vaccine based on human rotavirus strain with genotype G1P[8] for preventing rotavirus infection, and the RV5 pentavalent, live vaccine for preventing rotavirus infection and containing reassortant bovine and human rotavirus strains with genotypes G1, G2, G3, G4, and P[8] [4][5]. The WHO prequalification has been awarded to Rotavac® (G9P[11]) and Rotasil® (G1, G2, G3, G4, G9) vaccines, which will be soon available on the global market [6][7]. Russia has registered only the RV5 vaccine, which is recommended for use in accordance with the epidemiological indications1.

The 1.6 kpb VP6 gene encodes group and subgroup antigens. VP6 was the first protein used for rotavirus classification based on its serologic cross-reactivity and genetic variability. Group A rotaviruses are subdivided by using monoclonal antibodies into 4 subgroups (SGI, SGII, SG I + II and SG non-I, non-II) [8][9]. At present, based on the genetic diversity of VP6, 9 groups of rotavirus A-I are differentiated, which lately have acquired the status of species. Species A, B, C, and H have been isolated from humans, though, undoubtedly, the first of them has the highest public health significance worldwide [10][11]. The differences exceeding 19%, which were identified by the nucleotide sequence analysis, suggest different VP6 genotypes of group A rotavirus. To date, there are 26 known RVA VP6 genotypes (I1–I26) isolated from humans and animals. Despite the genotypic diversity of rotaviruses, the epidemically significant variants belong to 2 genogroups: Wa-like rotaviruses (genogroup 1) and DS-1-like rotaviruses (genogroup 2). In the RV1 vaccine containing a human Wa-like 89-12 rotavirus strain, the VP6 protein belongs to genogroup 1 (genotype I1). The RV5 vaccine (based on the DS-1-like bovine rotavirus WC3 strain) contains VP6 of genogroup 2 (genotype I2).

Patients who had RVI tend to demonstrate high titers of antibodies against the VP6 protein. The VP6 structure shows the presence of several B- and T-cell antigenic epitopes. The studies of antigenic properties of the protein have shown that the subgroup-specific epitopes are conformational and appear to be present only on the trimer surface, but not on the monomeric unit of the protein molecule. It has been found that a single mutation at positions 172 or 305 and 296–299 affects binding of antibodies to viruses from subgroup I (SGI) [12]. The double amino acid substitution at positions 305–306 and the single amino acid mutation at position 315 affect binding of antibodies recognizing the epitope of subgroup II (SGII) [12][13]. Aiyegbo et al. offered 2 tentative antigenic epitopes for intracellular antibodies located on VP6: A (amino acids, aa 231–260) and B (aa 265–292). The researchers found that by binding to a subviral double-layered particle inside a cell, human IgAs inhibited the rotavirus transcription [14].

The BEAST software incorporating the Bayesian evolutionary analysis and Markov chain Monte Carlo (MCMC) integration algorithm is used for analyzing phylogenetic trees built from the time-stamped genetic data [15]. This approach is efficient for evaluation of evolutionary processes in a population characterized by measurable changes that occurred over the time of sampling. The effective population size (Ne), one of the most critical parameters in the population genetics, converts the size of a real population into the size of an idealized population showing the same rate of change in the genetic variability as the real one [16]. In our study based on the VP6 gene of rotaviruses isolated in Russia, we have estimated such phylodynamic parameters as the rate of mutation accumulation, the time to the most recent common ancestor, the rate of changes in the effective population size over time. In addition, the studied sample was used for a comparative analysis of the amino acid composition for B- and T-cell epitopes of vaccine strains in RV1 and RV5 as well as wild-type strains isolated in Russia.

Material and methods

Sampling. Addressing allelic variations of the VP6 gene of the studied rotaviruses, we have analyzed nucleotide sequences available in the GenBank database and covering more than 80% of the open reading frame. The sample included nucleotide sequences of the VP6 gene in vaccine strains (RV1 and RV5) as well as 262 VP6 sequences of rotaviruses available in the GenBank and isolated in Nizhny Novgorod (23), Novosibirsk (203), Omsk (29), Smolensk (4), Khanty-Mansiysk (3), Russia, after 2010.

In the studied sample, 206 sequences of the VP6 gene belonged to genotype I1 and 56 sequences belonged to genotype I2. Gene sequences belonging to other RVA genotypes isolated in Russia were not available in the above database.

Phylodynamic analysis. Processing and alignment of nucleotide sequences as well as identification and analysis of amino acid sequences were performed by using the MEGA X software [17]. Since different genotypes can have different phylodynamic characteristics, the analysis of the temporal signal, estimation of the mutation accumulation rate and specific features of the population dynamics were assessed separately for sequences of genotypes I1 and I2. To build phylogenetic trees by using the maximum likelihood (ML) approach, we have selected the optimal model for the studied samples, T92+G+I. For initial estimation of the temporal signal based on the ML phylogenetic tree, we used a TempEst v1.5.3 software tool [18]. Both sets of data demonstrated positive correlation between the genetic distance and the sampling time, thus proving their suitability for the further Bayesian phylogenetic analysis. In addition, the analysis showed that the relaxed molecular clock should be used for the studied samples. The phylogenetic analysis was performed with a BEAST v.1.10.4 software package and BEAGLE v3.1.0 library [15][19]. The Hasegawa–Kishino–Yano (HKY) model was used for analyzing the nucleotide substitution process. The SkyGrid model was used to estimate the dynamics of demographic parameters [20]. Evolutionary rates were estimated by using the uncorrelated lognormal relaxed clock. To reach the effective sample size (ESS)>>200, the MCMC length was 80 million iterations. The visualization and processing of the phylogenetic trees were performed by using the FigTree v.1.4.3 program. The visualization of population dynamics and analysis of output MCMC files were performed with the Tracer v1.7.1 program [21].

Analysis of antigenic epitopes. B- and T-cell epitopes were searched through the international epitope database (IEDB; The study focused on epitopes identified in group A rotaviruses isolated from humans.


Phylogenetic analysis. To analyze clustering of Russian strains and their relationship with strains present in RV5 and RV1 vaccines by using the aggregate sample including genotypes I1 and I2, we have constructed a phylogenetic tree shown in Fig. 1. The RV1 vaccine strain is clustered separately from wild-type rotaviruses of the Russian origin. The posterior probability of a node with closest Russian variants included into the small group I1- 2 was 0.42, thus implying no significant evidence of the relatedness of these strains. Allele I1-1 includes most of the strains isolated in different regions of Russia in 2010– 2018. Genotype G4P[8] and G1P[8] strains isolated in Novosibirsk in 2010 belong to lineage I1-2. Group I1-3 included genotype G4P[6] rotaviruses also isolated in Novosibirsk (2010–2016).

Fig. 1
. Bayesian MCC phylogenetic tree based on the nucleotide sequences of the VP6 gene of Russian wild-type rotavirus samples’ strains and vaccine strains RV5 and RV1.
Note. MCC – maximum clade credibility phylogenetic tree.

In the phylogenetic tree, rotaviruses belonging to genogroup 2 are represented by 3 clusters (the posterior probability is 0.99), namely I2-1–I2-3. The RV5 vaccine strains belong to sublineage I2-2, which also includes 2 Novosibirsk isolates isolated in 2010. Most of the Russian RVAs of genogroup 2 belong to allele I2-1 by the VP6 gene. Sublineage I2-3 is represented by strains with genotype G3P[9], which were isolated in Nizhny Novgorod, Omsk, and Novosibirsk in 2010–2016.

Mutation rate and tMRCA. The mutation accumulation rate in Russian strains with genotype I1 was slightly lower than in I2 – 7.732E-4 and 1.008E-3, respectively (Table 1). The mutation rate varied insignificantly for each lineage within a genotype.

Table 1. Mutation rate and time of the most recent common ancestor (tMRCA) calculated based on Bayesian phylogenetic reconstruction

Note. HPD – highest posterior density interval.

The time to the most recent common ancestor (tMRCA) dates back to 1983 for cluster I1-1 including most of the group I1 RVAs of the Russian origin, 1973 for I1-2 (which included the strain present in the RV1 vaccine) and 1951 for strains of allele I1-3. Lineage I2-1, which includes most of the Russian RVAs of genogroup 2, has tMRCA dating back to 1992; lineage I2-2, which includes the RV5 vaccine strain, has tMRCA dating back to 1967. Allele I2-3 has the most recent common ancestor dated back to 1910 (Table 1).

Effective population size. The demographic history graphs, which were reconstructed by using nucleotide sequences of VP6 gene of Russian rotaviruses, the SkyGrid model and Bayesian analysis, do not offer the possibility to identify differences between the strains belonging to genogroups 1 and 2 (Fig. 2). Both populations are characterized by long-term stable characteristics. Rotaviruses with genotype I1 demonstrated a slight increase in Ne to turn into a downward trend in 2000. Likewise, RVAs with genotype I2 showed a slight decrease in the effective population size at the same time.

Fig. 2
. Demographic history of the I1 and I2 VP6 gene. The x-axis shows time in calendar years. The y-axis shows the effective population size of the virus (Ne), representing the number of genomes that are effective for the development of new infections. The line in the center represents median values within 95% of the target density range.

B-cell antigenic epitopes of the VP6 protein. The RV1 vaccine is based on the attenuated human rotavirus strain with genotype G1P[8]. The VP6 gene has genotype I1 and belongs to genogroup 1. RV5 is a reassortant pentavalent vaccine based on bovine and human rotavirus strains. VP6 present in it belongs to the bovine rotavirus of genotype I2.

Epitope A is made up of 30 amino acid residues (231–260 aa). In this region, the amino acid composition of RV1 and RV5 vaccines is 1 amino acid different at position F248Y (Fig. 3). The wild-type strains isolated in Russia differ from vaccine strains by single mutations in individual strains. At position 252, a number of Russian samples (169 out of 180 sequences) belonging to genogroup 1 have V252I substitution. Genogroup 2, as well as RV1 and RV5, has valine (Val) at that position. This amino acid mutation is not connected with any lineage or cluster in the phylogenetic tree.

Fig. 3
. Amino acid composition of antigenic epitopes A (231–260 aa) and B (265–292 aa) of VP6 protein of Russian wild-type rotavirus strains and strains in the RV5 and RV1 vaccines.

Epitope B is made up of 28 amino acid residues (265–292 aa). In RV1 and RV5 vaccines, the amino acid composition is different at position S291L; both vaccines have isoleucine (Ile) at position 281; however, in both genogroups, wild-type strains are characterized by substitution for valine (Val) (38 isolates of genotype I1 and 26 isolates of genotype I2), which is also not connected with the phylogenetic characteristics of strains.

Thus, the analysis of the VP6 amino acid sequence in the tentative antigenic epitopes A and B demonstrated high conservation of the amino acid composition both in the vaccine strains and RVA strains isolated in Russia, even though they belong to different genogroups.

The studied sample was used to demonstrate amino acid differences at positions specific for antibodies belonging to subgroups I and II: M172A, N305A, and Q315E correlation with genogroup 1 or 2. Sites 296–299 and 306 aa, which are responsible for binding of specific subgroup antibodies, were conservative in all the studied isolates.

Analysis of T-cell epitopes. Using the sample of RVA strains isolated in Russia to study linear epitopes made it possible to identify only single mutations of wild-type strains as compared to vaccine strains. The amino acid differences at positions N305A, Q315E, L342M, and A348S correlate with genogroups 1 and 2, respectively. At position L291S, the RV1 vaccine strain bears leucine (Leu), while RV5 strains and Russian samples have serine (Ser). Generally, these sites are highly conservative and no point mutations were found in the strains of the Russian origin (Fig. 4).

Fig. 4
. Amino acid sequences of protein VP6 linear epitopes of vaccine strains RV1, RV5 and Russian wild-type RVA strains.


VP6, a highly conservative protein of the inner capsid of the virion, is both an antigenic protein and an immunogen [13][22][23][24][25]. Its native conformation in the expressed and purified form represents an oligomer. The further assembly of trimeric molecules into morphological structures occurs spontaneously; it does not require any interaction with other viral proteins or subviral structures [26]. The self-organizing VP6 inducing an immune response is increasingly being seen as a prospective vaccine candidate [27].

Currently, there are no Russian vaccines against RVI. Manufacturing of live vaccines is a labor-intensive, long, and costly process involving strict requirements for delivery of the ready-to-use vaccine to a patient. Another challenge associated with vaccines is their safety when using for children with immune deficiencies and the subsequent risk of development of vaccine-associated gastroenteritis as well as the risk of intussusception. One of the new paradigms implies non-replicating vaccines, including vaccines based on the VP6 protein. Therefore, a number of research groups both in Russia and other countries are working on designing recombinant constructs [28][29][30].

This study was the first to give molecular-genetic description of Russian and vaccine rotavirus A strains based on the VP6 gene. To estimate the evolutionary relationship between the Russian wild-type rotaviruses and the strains present in RV1 and RV5 vaccines, we reconstructed phylogenetic trees and used the Bayesian statistics. The phylogenetic analysis based on VP6 gene nucleotide sequences in Russian RVAs demonstrated the presence of three sublineages within genotype I1 (I1-1–I1-3) and 3 sublineages within genotype I2 (I2-1–I2-3). It has been found that most of the Russian RVAs bear alleles I1-1 and I2-1 of the VP6 gene.

Previously, a number of authors obtained data describing mutation accumulation rates for different genes of the group A rotavirus. The obtained results may vary within a certain range, as they are highly affected by the size and composition of a sample. In our study, the mutation accumulation rate for Russian RVAs of genotype I1 (7.732E-4) differed insignificantly from the rate estimated for I2 (1.008Е-3).

The effective population size (Ne) is a generalized parameter used for measuring the size of the studied, specific population based on genetic variability within an idealized model and for reconstructing the previous population dynamics [31]. This parameter provides a quantitative estimate of genetic variability and its temporal variations by using studied genomic data. The analysis of the effective population size can be used for retrospective identification of the epidemic outbreak time as well as for monitoring of the operating efficiency of the involved agencies and efficiency of the adopted measures aimed at prevention of the infection [32][33]. In our study, based on nucleotide sequences of VP6 gene of Russian rotaviruses, we have shown the decrease in the Ne parameter for the RVA population after the 2000s, which implies a reduction in the VP6 genetic variability. These data are supported by the phylogenetic analysis: most of the Russian wild-type rotaviruses isolated in 2010–2018 bear alleles I1-1 and I2-1. Clusters I1-2, I1-3, I2-2, and I2-3 contained vaccine strains and few isolates having no wide-spread occurrence. When vaccination is characterized by low coverage, the decrease in Ne can also be associated with the cyclic pattern of the epidemic process, which implies the natural decrease in the circulation of the dominant type, as was shown earlier by the example of the Nizhny Novgorod RVA population [34].

Numerous studies address the comparative analysis where neutralizing epitopes of VP7 and VP4 proteins in RVAs isolated in different territories are compared with RV1 and RV5 vaccine strains [35][36][37]. However, as such studies tend to ignore the VP6 protein, we compared the amino acid composition of antigenic epitopes of VP6 protein strains present in RV1 and RV5 and the amino acid composition of the rotaviruses isolated in Russia after 2010. The analysis of the amino acid composition of antigenic VP6 epitopes indicates high conservation of antigenic determinants in vaccine strains and wild-type strains isolated in Russia, though they were isolated in different time periods. High conservation has been found in rotaviruses belonging to genogroups 1 and 2, which prevail among RVAs isolated from humans. The identified amino acid differences in the VP6 protein are most likely associated with the genotype status of the strain and do not involve its immunological properties. On the one hand, this observation turns the VP6 protein into a promising model for vaccine development; on the other hand, its significance in building robust and stable protective immunity is not conclusive.


Thus, the analysis of the phylodynamic characteristics of VP6 nucleotide sequences and the study of the identified amino acid sequences in antigenic epitopes have demonstrated high conservation of the inner capsid protein, this turning it into a promising model for development of a universal rotavirus vaccine.


About the authors

O. V. Morozova

FSBI «Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare

Author for correspondence.
ORCID iD: 0000-0002-8058-8187

researcher of Laboratory of Molecular Epidemiology of Viral Infections

Nizhny Novgorod, 603950

Russian Federation

T. F. Sashina

FSBI «Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare

ORCID iD: 0000-0003-3203-7863

senior Researcher, laboratory of molecular epidemiology of viral infections

Nizhny Novgorod, 603950

Russian Federation

N. A. Novikova

FSBI «Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare

ORCID iD: 0000-0002-3710-6648

professor. Head of the laboratory of molecular epidemiology of viral infections

Nizhny Novgorod, 603950

Russian Federation


  1. Tate J.E., Burton A.H., Boschi-Pinto C., Steele A.D., Duque J., Parashar U.D. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect. Dis. 2012; 12(2): 136–41.
  2. Баранов А.А., Намазова-Баранова Л.С., Таточенко В.К., Вишнёва Е.А., Федосеенко М.В., Селимзянова Л.Р. и др. Ротавирусная инфекция у детей – нерешённая проблема. Обзор рекомендаций по вакцинопрофилактике. Педиатрическая фармакология. 2017; 14(4): 248–57.
  3. Mirzayeva R., Cortese M.M., Mosina L., Biellik R., Lobanov A., Chernyshova L., et al. Rotavirus burden among children in the newly independent states of the former union of soviet socialist republics: literature review and first-year results from the rotavirus surveillance network. J. Infect. Dis. 2009; 200 (Suppl. 2): S203–14.
  4. Ward R.L., Bernstein D.I. Rotarix: A rotavirus vaccine for the world. Clin. Infect. Dis. 2009; 48(2): 222–8.
  5. Ciarlet M., Schödel F. Development of a rotavirus vaccine: Clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq. Vaccine. 2009; 27(Suppl. 6): G72–81.
  6. Glass R.I., Bhan M.K., Ray P., Bahl R., Parashar U.D., Greenberg H., et al. Development of candidate rotavirus vaccines derived from neonatal strains in India. J. Infect. Dis. 2005; 192(Suppl. 1): S30–5.
  7. Naik S.P., Zade J.K., Sabale R.N., Pisal S.S., Menon R., Bankar S.G., et al. Stability of heat stable, live attenuated Rotavirus vaccine (ROTASIIL®). Vaccine. 2017; 35(22): 2962–9.
  8. Greenberg H.B., Flores J., Kalica A.R., Wyatt R.G., Jones R. Gene coding assignments for growth restriction, neutralization and subgroup specificities of the W and DS-1 strains of human rotavirus. J. Gen. Virol. 1983; 64 (Pt. 2): 313–20.
  9. Iturriza Gómara M., Wong C., Blome S., Desselberger U., Gray J. Molecular characterization of VP6 genes of human rotavirus isolates: correlation of genogroups with subgroups and evidence of independent segregation. J. Virol. 2002; 76(13): 6596–601.
  10. Estes M.K., Greenberg H.B. Rotaviruses. In: Knipe D.M., Howley P.M., eds. Fields Virology. Philadelphia: Williams & Wilkins; 2013:1347–401.
  11. Nagashima S., Kobayashi N., Ishino M., Alam M.M., Ahmed M.U., Paul S.K., et al. Whole genomic characterization of a human rotavirus strain B219 belonging to a novel group of the genus Rotavirus. J. Med. Virol. 2008; 80(11): 2023–33.
  12. López S., Espinosa R., Greenberg H.B., Arias C.F. Mapping the subgroup epitopes of rotavirus protein VP6. Virology. 1994; 204(1):153–62.
  13. Tang B., Gilbert J.M., Matsui S.M., Greenberg H.B. Comparison of the rotavirus gene 6 from different species by sequence analysis and localization of subgroup-specific epitopes using site-directed mutagenesis. Virology. 1997; 237(1): 89–96.
  14. Aiyegbo M.S., Sapparapu G., Spiller B.W., Eli I.M., Williams D.R., Kim R., et al. Human rotavirus VP6-specific antibodies mediate intracellular neutralization by binding to a quaternary structure in the transcriptional pore. PLoS One. 2013; 9(8): 1–15.
  15. Suchard M.A., Lemey P., Baele G., Ayres D.L., Drummond A.J., Rambaut A. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol. 2018; 4(1): vey016.
  16. Husemann M., Zachos F.E., Paxton R.J., Habel J.C. Effective population size in ecology and evolution. Heredity. 2016; 117(4): 191–2.
  17. Kumar S., Stecher G., Li M., Knyaz C., Tamura K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol. 2018; 35(6): 1547–9.
  18. Rambaut A., Lam T.T., Max Carvalho L., Pybus O.G. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evol. 2016; 2(1): vew007.
  19. Ayres D.L., Cummings M.P., Baele G., Darling A.E., Lewis P.O., Swofford D.L., et al. BEAGLE 3: improved performance, scaling and usability for a high-performance computing library for statistical phylogenetics. Syst. Biol. 2019; 68(6): 1052–61.
  20. Hill V., Baele G. Bayesian estimation of past population dynamics in BEAST 1.10 using the Skygrid coalescent model. Mol. Biol. Evol. 2019; 36(11): 2620–8.
  21. Rambaut A., Drummond A.J., Xie D., Baele G., Suchard M.A. Posterior summarization in Bayesian phylogenetics using Tracer 1.7. Syst. Biol. 2018; 67(5): 901–4.
  22. Svensson L., Sheshberadaran H., Vene S., Norrby E., Grandien M., Wadell G. Serum antibody responses to individual viral polypeptides in human rotavirus infections. J. Gen. Virol. 1987; 68(Pt. 3): 643–51.
  23. Svensson L., Sheshberadaran H., Vesikari T., Norrby E., Wadell G. Immune response to rotavirus polypeptides after vaccination with heterologous rotavirus vaccines (RIT 4237, RRV‑1). J. Gen. Virol. 1987; 68(Pt. 7): 1993–9.
  24. Ishida S., Feng N., Tang B., Gilbert J.M., Greenberg H.B. Quantification of systemic and local immune responses to individual rotavirus proteins during rotavirus infection in mice. J. Clin. Microbiol. 1996; 34(7): 1694–700.
  25. Colomina J., Gil M.T., Codoñer P., Buesa J. Viral proteins VP2, VP6, and NSP2 are strongly precipitated by serum and fecal antibodies from children with rotavirus symptomatic infection. J. Med. Virol. 1998; 56(1): 58–65.<58::aid-jmv10>;2-s.
  26. Estes M.K., Cohen J. Rotavirus gene structure and function. Microbiol. Rev. 1989; 53(4): 410–49.
  27. Afchangi A., Jalilvand S., Mohajel N., Marashi S.M., Shoja Z. Rotavirus VP6 as a potential vaccine candidate. Rev. Med. Virol. 2019; 29(2): e2027.
  28. Духовлинов И.В., Богомолова Е.Г., Фёдорова Е.А., Симбирцев А.С. Исследование протективной активности кандидатной вакцины против ротавирусной инфекции на основе рекомбинантного белка FliCVP6VP8. Медицинская иммунология. 2016; 18(5): 417–24.
  29. Choi A.H., McNeal M.M., Basu M., Flint J.A., Stone S.C., Clements J.D., et al. Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses. Vaccine. 2002; 20(27-28): 3310–21.
  30. McNeal M.M., Basu M., Bean J.A., Clements J.D., Lycke N.Y., Ramne A., et al. Intrarectal immunization of mice with VP6 and either LT(R192G) or CTA1-DD as adjuvant protects against fecal rotavirus shedding after EDIM challenge. Vaccine. 2007; 25(33):6224–31.
  31. Gill M.S., Lemey P., Faria N.R., Rambaut A., Shapiro B., Suchard M.A. Improving Bayesian population dynamics inference: a coalescent- based model for multiple loci. Mol. Biol. Evol. 2013; 30(3):713–24.
  32. Faria N.R., Suchard M.A., Abecasis A., Sousa J.D., Ndembi N., Camacho R.J., et al. Phylodynamics of the HIV-1 CRF02_AG clade in Cameroon. Infect. Genet. Evol. 2012; 12(2): 453–60.
  33. Rambaut A., Pybus O.G., Nelson M.I., Viboud C., Taubenberger J.K., Holmes E.C. The genomic and epidemiological dynamics of human influenza A virus. Nature. 2008; 453(7195): 615–9.
  34. Новикова Н.А., Епифанова Н.В., Фёдорова О.Ф. Цикличность эпидемического процесса ротавирусного гастроэнтерита и ее причины. В кн.: Материалы научной конференции «Новые технологии в профилактике, диагностике, эпиднадзоре и лечении инфекционных заболеваний». Н. Новгород; 2004: 74–7.
  35. Zeller M., Patton J.T., Heylen E., De Coster S., Ciarlet M., Van Ranst M., et al. Genetic analyses reveal differences in the VP7 and VP4 antigenic epitopes between human rotaviruses circulating in Belgium and rotaviruses in Rotarix and RotaTeq. J. Clin. Microbiol. 2012; 50(3): 966–76.
  36. Morozova O.V., Sashina T.A., Fomina S.G., Novikova N.A. Comparative characteristics of the VP7 and VP4 antigenic epitopes of the rotaviruses circulating in Russia (Nizhniy Novgorod) and the Rotarix and RotaTeq vaccines. Arch. Virol. 2015; 160(7): 1693–703.
  37. Motamedi-Rad M., Farahmand M., Arashkia A., Jalilvand S., Shoja Z. VP7 and VP4 genotypes of rotaviruses cocirculating in Iran, 2015 to 2017: Comparison with cogent sequences of Rotarix and RotaTeq vaccine strains before their use for universal mass vaccination. J. Med. Virol. 2020; 92(8): 1110–23.

Copyright (c) 2021 Morozova O.V., Sashina T.F., Novikova N.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС77-77676 от 29.01.2020.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies