Voprosy virusologii最新文献

The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea.

Materials and methods: Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus.

Results and discussion: In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified.

Conclusion: The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.

Introduction: The countries of Central Asia, including Kyrgyzstan, are characterized by high prevalence and morbidity of HCV infection. Identification of HCV genotype and mutations associated with resistance to direct-acting antiviral (DAA) plays an important role either in conducting molecular epidemiological studies or choosing the treatment tactics. The aim of the work was to research of the genotype diversity of HCV variants circulating in Kyrgyzstan and the identification among them the mutations associated with the development of resistance to DAA.

Materials and methods: 38 serum samples from HCV-infected residents of Kyrgyzstan were analyzed in this study. The nucleotide sequences of viral gene fragments (NS3, NS5A, NS5B) were determined by Sangers sequencing and deposited in the international GenBank database under the numbers ON841497ON841534 (NS5B), ON841535ON841566 (NS5A), and ON841567ON841584 (NS3).

Results: The HCV subtypes 1b (52.6%; 95% CI 37.367.5%), 3a (44.8%; 95% CI 30.260.2%) and 1a (2.6%; 95% CI 0.513.4%) are circulating in Kyrgyzstan. 37% (95% CI 1959%) of subtype 1b isolates had C316N mutation in the NS5A gene; 46% (95% CI 2370%) had F37L mutation in the NS5A gene; 45% (95% CI 2272%) had Y56F mutation in the NS3 gene. Among subtype 3a isolates, resistance-associated mutations in NS5B fragment were not found. 22% (95% CI 945%) of subtype 3a sequences had a Y93H mutation in the NS5A gene. A combination of Y56F + Q168 + I170 mutations was identified among all sequences of NS3 gene. DAA resistance mutations were not found in NS3, NS5A, NS5B genes of subtype 1a sequence.

Conclusion: A rather high prevalence of mutations associated with resistance or significant decrease in sensitivity to DAA among HCV sequences from Kyrgyzstan was shown. Updating of data on HCV genetic diversity is necessary for timely planning of measures to combat epidemic.

Introduction: Intranasal vaccination using live vector vaccines based on non-pathogenic or slightly pathogenic viruses is the one of the most convenient, safe and effective ways to prevent respiratory infections, including COVID-19. Sendai virus is the best suited for this purpose, since it is respiratory virus and is capable of limited replication in human bronchial epithelial cells without causing disease. The aim of the work is to design and study the vaccine properties of recombinant Sendai virus, Moscow strain, expressing secreted receptor-binding domain of SARS-CoV-2 Delta strain S protein (RBDdelta) during a single intranasal immunization.

Materials and methods: Recombinant Sendai virus carrying insertion of RBDdelta transgene between P and M genes was constructed using reverse genetics and synthetic biology methods. Expression of RBDdelta was analyzed by Western blot. Vaccine properties were studied in two models: Syrian hamsters and BALB/c mice. Immunogenicity was evaluated by ELISA and virus-neutralization assays. Protectiveness was assessed by quantitation of SARS-CoV-2 RNA in RT-PCR and histological analysis of the lungs.

Results: Based on Sendai virus Moscow strain, a recombinant Sen-RBDdelta(M) was constructed that expressed a secreted RBDdelta immunologically identical to natural SARS-CoV-2 protein. A single intranasal administration of Sen-RBDdelta(M) to hamsters and mice significantly, by 15 and 107 times, respectively, reduced replicative activity of SARS-CoV-2 in lungs of animals, preventing the development of pneumonia. An effective induction of virus-neutralizing antibodies has also been demonstrated in mice.

Conclusion: Sen-RBDdelta(M) is a promising vaccine construct against SARS-CoV-2 infection and has a protective properties even after a single intranasal introduction.