Viruses

Research

13 pages, 950 KiB

Open AccessArticle

Enteroviruses Manipulate the Unfolded Protein Response through Multifaceted Deregulation of the Ire1-Xbp1 Pathway

by Anna Shishova, Ilya Dyugay, Ksenia Fominykh, Victoria Baryshnikova, Alena Dereventsova, Yuriy Turchenko, Anna A. Slavokhotova, Yury Ivin, Sergey E. Dmitriev and Anatoly Gmyl

Viruses 2022, 14(11), 2486; https://doi.org/10.3390/v14112486 - 10 Nov 2022

Cited by 8 | Viewed by 2394

Abstract

Many viruses are known to trigger endoplasmic reticulum (ER) stress in host cells, which in turn can develop a protective unfolded protein response (UPR). Depending on the conditions, the UPR may lead to either cell survival or programmed cell death. One of three [...] Read more.

Many viruses are known to trigger endoplasmic reticulum (ER) stress in host cells, which in turn can develop a protective unfolded protein response (UPR). Depending on the conditions, the UPR may lead to either cell survival or programmed cell death. One of three UPR branches involves the upregulation of Xbp1 transcription factor caused by the unconventional cytoplasmic splicing of its mRNA. This process is accomplished by the phosphorylated form of the endoribonuclease/protein kinase Ire1/ERN1. Here, we show that the phosphorylation of Ire1 is up-regulated in HeLa cells early in enterovirus infection but down-regulated at later stages. We also find that Ire1 is cleaved in poliovirus- and coxsackievirus-infected HeLa cells 4–6 h after infection. We further show that the Ire1-mediated Xbp1 mRNA splicing is repressed in infected cells in a time-dependent manner. Thus, our results demonstrate the ability of enteroviruses to actively modulate the Ire1-Xbp1 host defensive pathway by inducing phosphorylation and proteolytic cleavage of the ER stress sensor Ire1, as well as down-regulating its splicing activity. Inactivation of Ire1 could be a novel mode of the UPR manipulation employed by viruses to modify the ER stress response in the infected cells. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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12 pages, 1068 KiB

Open AccessArticle

Simultaneous Detection of RIG-1, MDA5, and IFIT-1 Expression Is a Convenient Tool for Evaluation of the Interferon-Mediated Response

by Alexey A. Lozhkov, Marina A. Plotnikova, Marya A. Egorova, Irina L. Baranovskaya, Ekaterina A. Elpaeva, Sergey A. Klotchenko and Andrey V. Vasin

Viruses 2022, 14(10), 2090; https://doi.org/10.3390/v14102090 - 21 Sep 2022

Cited by 4 | Viewed by 2649

Abstract

In this study, we developed a novel, multiplex qPCR assay for simultaneous detection of RIG-1, MDA5, and IFIT-1 at the mRNA level. The assay was validated in A549 cells transfected with in vitro transcribed RNAs. Both exogenous RNA-GFP and self-amplifying (saRNA-GFP) induced significant [...] Read more.

In this study, we developed a novel, multiplex qPCR assay for simultaneous detection of RIG-1, MDA5, and IFIT-1 at the mRNA level. The assay was validated in A549 cells transfected with in vitro transcribed RNAs. Both exogenous RNA-GFP and self-amplifying (saRNA-GFP) induced significant expression of RIG-1, MDA5, IFIT-1, as well as type I and III interferons. In contrast, native RNA from intact A549 cells did not upregulate expression of these genes. Next, we evaluated RIG-1, MDA5, and IFIT-1 mRNA levels in the white blood cells of patients with influenza A virus (H3N2) or SARS-CoV-2. In acute phase (about 4 days after disease onset) both viruses induced these genes expression. Clinical observations of SARS-CoV-2 typically describe a two-step disease progression, starting with a mild-to-moderate presentation followed by a secondary respiratory worsening 9 to 12 days after the first onset of symptoms. It revealed that the expression of RIG-1, MDA5, and MxA was not increased after 2 and 3 weeks from the onset the disease, while for IFIT-1 it was observed the second peak at 21 day post infection. It is well known that RIG-1, MDA5, and IFIT-1 expression is induced by the action of interferons. Due to the ability of SOCS-1 to inhibit interferon-dependent signaling, and the distinct antagonism of SARS-CoV-2 in relation to interferon-stimulated genes expression, we assessed SOCS-1 mRNA levels in white blood cells. SARS-CoV-2 patients had increased SOCS-1 expression, while the influenza-infected group did not differ from heathy donors. Moreover, SOCS-1 mRNA expression remained stably elevated during the course of the disease. It can be assumed that augmented SOCS-1 expression is one of multiple mechanisms that allow SARS-CoV-2 to escape from the interferon-mediated immune response. Our results implicate SOCS-1 involvement in the pathogenesis of SARS-CoV-2. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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16 pages, 2303 KiB

Open AccessArticle

Double and Triple Combinations of Broadly Neutralizing Antibodies Provide Efficient Neutralization of All HIV-1 Strains from the Global Panel

by Evgeniya A. Kochina, Felix A. Urusov, Artem A. Kruglov, Dina V. Glazkova, German A. Shipulin and Elena V. Bogoslovskaya

Viruses 2022, 14(9), 1910; https://doi.org/10.3390/v14091910 - 29 Aug 2022

Cited by 4 | Viewed by 2622

Abstract

The use of broadly neutralizing antibodies (bNAbs) is a promising approach to HIV-1 treatment. In this work, we evaluate the neutralizing activity of the following HIV-1 bNAbs: VCR07-523, N6, PGDM1400, CAP256-VRC26.25, 10-1074, PGT128, 10E8, and DH511.11P, which are directed to different Env surface [...] Read more.

The use of broadly neutralizing antibodies (bNAbs) is a promising approach to HIV-1 treatment. In this work, we evaluate the neutralizing activity of the following HIV-1 bNAbs: VCR07-523, N6, PGDM1400, CAP256-VRC26.25, 10-1074, PGT128, 10E8, and DH511.11P, which are directed to different Env surface epitopes. We used the global panel of HIV-1 pseudoviruses to analyze the bNAbs’ potency and chose the most potent ones. To achieve maximum neutralization breadth and minimum IC₅₀ concentration, the most effective antibodies were tested in double and triple combinations. Among the doubles, the combinations of N6+PGDM1400 and N6+PGT128 with IC₅₀ ≤ 0.3 µg/mL proved to be the most effective. The most effective triple combination was N6+PGDM1400+PGT128. Our data demonstrate that this combination neutralizes pseudoviruses of the global HIV-1 panel with IC₅₀ ≤ 0.11 µg/mL and IC₈₀ ≤ 0.25 µg/mL. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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15 pages, 2140 KiB

Open AccessArticle

Resurgence of Influenza Circulation in the Russian Federation during the Delta and Omicron COVID-19 Era

by Anna Sominina, Daria Danilenko, Andrey Komissarov, Ludmila Karpova, Maria Pisareva, Artem Fadeev, Nadezhda Konovalova, Mikhail Eropkin, Kirill Stolyarov, Anna Shtro, Elena Burtseva and Dmitry Lioznov

Viruses 2022, 14(9), 1909; https://doi.org/10.3390/v14091909 - 29 Aug 2022

Cited by 12 | Viewed by 2333

Abstract

Influenza circulation was substantially reduced after March 2020 in the European region and globally due to the wide introduction of non-pharmaceutical interventions (NPIs) against COVID-19. The virus, however, has been actively circulating in natural reservoirs. In summer 2021, NPIs were loosened in Russia, [...] Read more.

Influenza circulation was substantially reduced after March 2020 in the European region and globally due to the wide introduction of non-pharmaceutical interventions (NPIs) against COVID-19. The virus, however, has been actively circulating in natural reservoirs. In summer 2021, NPIs were loosened in Russia, and influenza activity resumed shortly thereafter. Here, we summarize the epidemiological and virological data on the influenza epidemic in Russia in 2021–2022 obtained by the two National Influenza Centers. We demonstrate that the commonly used baseline for acute respiratory infection (ARI) is no longer sufficiently sensitive and BL for ILI incidence was more specific for early recognition of the epidemic. We also present the results of PCR detection of influenza, SARS-CoV-2 and other respiratory viruses as well as antigenic and genetic analysis of influenza viruses. Influenza A(H3N2) prevailed this season with influenza B being detected at low levels at the end of the epidemic. The majority of A(H3N2) viruses were antigenically and genetically homogenous and belonged to the clade 3C.2a1b.2a.2 of the vaccine strain A/Darwin/9/2021 for the season 2022–2023. All influenza B viruses belonged to the Victoria lineage and were similar to the influenza B/Austria/1359417/2021 virus. No influenza A(H1N1)pdm09 and influenza B/Yamagata lineage was isolated last season. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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23 pages, 2768 KiB

Open AccessArticle

Heterogenous CD8+ T Cell Maturation and ‘Polarization’ in Acute and Convalescent COVID-19 Patients

by Igor V. Kudryavtsev, Natalia A. Arsentieva, Zoia R. Korobova, Dmitry V. Isakov, Artem A. Rubinstein, Oleg K. Batsunov, Irina V. Khamitova, Raisa N. Kuznetsova, Tikhon V. Savin, Tatiana V. Akisheva, Oksana V. Stanevich, Aleksandra A. Lebedeva, Evgeny A. Vorobyov, Snejana V. Vorobyova, Alexander N. Kulikov, Maria A. Sharapova, Dmitrii E. Pevtsov and Areg A. Totolian

Viruses 2022, 14(9), 1906; https://doi.org/10.3390/v14091906 - 28 Aug 2022

Cited by 23 | Viewed by 3178

Abstract

Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. [...] Read more.

Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. Methods.. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. Results. Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on ‘naïve’, CM, EM4, and pE1 2–3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. Conclusions. We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on ‘naïve’ and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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12 pages, 1927 KiB

Open AccessArticle

Effective Approaches to Study the Genetic Variability of SARS-CoV-2

by Ivan Kotov, Valeriia Saenko, Nadezhda Borisova, Anton Kolesnikov, Larisa Kondrasheva, Elena Tivanova, Kamil Khafizov and Vasily Akimkin

Viruses 2022, 14(9), 1855; https://doi.org/10.3390/v14091855 - 24 Aug 2022

Cited by 4 | Viewed by 2122

Abstract

Significant efforts are being made in many countries around the world to respond to the COVID-19 pandemic by developing diagnostic reagent kits, identifying infected people, determining treatment methods, and finally producing effective vaccines. However, novel coronavirus variants may potentially reduce the effectiveness of [...] Read more.

Significant efforts are being made in many countries around the world to respond to the COVID-19 pandemic by developing diagnostic reagent kits, identifying infected people, determining treatment methods, and finally producing effective vaccines. However, novel coronavirus variants may potentially reduce the effectiveness of all these efforts, demonstrating increased transmissibility and abated response to therapy or vaccines, as well as the possibility of false negative results in diagnostic procedures based on nucleic acid amplification methods. Since the end of 2020, several variants of concern have been discovered around the world. When information about a new, potentially more dangerous strain of pathogen appears, it is crucial to determine the moment of its emergence in a region. Eventually, that permits taking timely measures and minimizing new risks associated with the spreading of the virus. Therefore, numerous nations have made tremendous efforts to identify and trace these virus variants, which necessitates serious technological processes to sequence a large number of viral genomes. Here, we report on our experience as one of the primary laboratories involved in monitoring SARS-CoV-2 variants in Russia. We discuss the various approaches used, describe effective protocols, and outline a potential technique combining several methods to increase the ability to trace genetic variants while minimizing financial and labor costs. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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17 pages, 3222 KiB

Open AccessArticle

Autoimmune Effect of Antibodies against the SARS-CoV-2 Nucleoprotein

by Daria Matyushkina, Varvara Shokina, Polina Tikhonova, Valentin Manuvera, Dmitry Shirokov, Daria Kharlampieva, Vasily Lazarev, Anna Varizhuk, Tatiana Vedekhina, Alexander Pavlenko, Leonid Penkin, Georgij Arapidi, Konstantin Pavlov, Dmitry Pushkar, Konstantin Kolontarev, Alexander Rumyantsev, Sergey Rumyantsev, Lyubov Rychkova and Vadim Govorun

Viruses 2022, 14(6), 1141; https://doi.org/10.3390/v14061141 - 25 May 2022

Cited by 10 | Viewed by 4712

Abstract

COVID-19 caused by SARS-CoV-2 is continuing to spread around the world and drastically affect our daily life. New strains appear, and the severity of the course of the disease itself seems to be decreasing, but even people who have been ill on an [...] Read more.

COVID-19 caused by SARS-CoV-2 is continuing to spread around the world and drastically affect our daily life. New strains appear, and the severity of the course of the disease itself seems to be decreasing, but even people who have been ill on an outpatient basis suffer post-COVID consequences. Partly, it is associated with the autoimmune reactions, so debates about the development of new vaccines and the need for vaccination/revaccination continue. In this study we performed an analysis of the antibody response of patients with COVID-19 to linear and conformational epitopes of viral proteins using ELISA, chip array and western blot with analysis of correlations between antibody titer, disease severity, and complications. We have shown that the presence of IgG antibodies to the nucleoprotein can deteriorate the course of the disease, induce multiple direct COVID-19 symptoms, and contribute to long-term post-covid symptoms. We analyzed the cross reactivity of antibodies to SARS-CoV-2 with own human proteins and showed that antibodies to the nucleocapsid protein can bind to human proteins. In accordance with the possibility of HLA presentation, the main possible targets of the autoantibodies were identified. People with HLA alleles A01:01; A26:01; B39:01; B15:01 are most susceptible to the development of autoimmune processes after COVID-19. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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12 pages, 979 KiB

Open AccessArticle

Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

by Iuliia A. Merkuleva, Dmitry N. Shcherbakov, Mariya B. Borgoyakova, Anastasiya A. Isaeva, Valentina S. Nesmeyanova, Natalia V. Volkova, Vazirbek S. Aripov, Daniil V. Shanshin, Larisa I. Karpenko, Svetlana V. Belenkaya, Elena I. Kazachinskaia, Ekaterina A. Volosnikova, Tatiana I. Esina, Alexandr A. Sergeev, Kseniia A. Titova, Yulia V. Konyakhina, Anna V. Zaykovskaya, Oleg V. Pyankov, Evgeniia A. Kolosova, Olesya E. Viktorina, Arseniya A. Shelemba, Andrey P. Rudometov and Alexander A. Ilyichev Show full author list Hide full author list

Viruses 2022, 14(5), 1060; https://doi.org/10.3390/v14051060 - 16 May 2022

Cited by 11 | Viewed by 2744

Abstract

Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, [...] Read more.

Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, rabbits, ferrets, and chickens) for RBD immunogenicity assessments. The humoral immune response was evaluated by ELISA and virus-neutralization assays. The data obtained show hamsters to be the least suitable candidates for RBD immunogenicity testing and, hence, assessing the protective efficacy of RBD-based vaccines. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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11 pages, 2554 KiB

Open AccessArticle

Infectivity and Morphology of Bovine Coronavirus Inactivated In Vitro by Cationic Photosensitizers

by Vladimir Zhukhovitsky, Natalia Shevlyagina, Margarita Zubasheva, Leonid Russu, Vladimir Gushchin, Gennady Meerovich and Marina Strakhovskaya

Viruses 2022, 14(5), 1053; https://doi.org/10.3390/v14051053 - 15 May 2022

Cited by 8 | Viewed by 2598

Abstract

Bovine coronaviruses (BCoVs), which cause gastrointestinal and respiratory diseases in cattle, and are genetically related to the human coronavirus HCoV-OC43, which is responsible for up to 10% of common colds, attract increased attention. We applied the method of photodynamic inactivation with cationic photosensitizers [...] Read more.

Bovine coronaviruses (BCoVs), which cause gastrointestinal and respiratory diseases in cattle, and are genetically related to the human coronavirus HCoV-OC43, which is responsible for up to 10% of common colds, attract increased attention. We applied the method of photodynamic inactivation with cationic photosensitizers (PSs) to reduce the titers of BCoV and studied the morphological structure of viral particles under various modes of photodynamic exposure. The samples of virus containing liquid with an initial virus titer of 5 Log₁₀ TCID50/mL were incubated with methylene blue (MB) or octakis(cholinyl)zinc phthalocyanine (Zn-PcChol₈₊) at concentrations of 1–5 μM for 10 min in the dark at room temperature. After incubation, samples were irradiated with LED (emission with maximum at 663 nm for MB or at 686 nm for Zn-PcChol₈₊) with light doses of 1.5 or 4 J/cm². Next, the irradiation titrated virus containing liquid was studied using negative staining transmission electron microscopy. MB and Zn-PcChol₈₊ at concentrations of 1–5 μM, in combination with red light from LED sources in the low doses of 1.5–4.0 J/cm², led to a decrease in BCoV titers by at least four orders of magnitude from the initial titer 5 Log₁₀ TCID50/mL. Morphological changes in photodamaged BCoVs with increasing PS concentrations were loss of spikes, change in shape, decreased size of virus particles, destruction of the envelope, and complete disintegration of viruses. BCoV has been found to be sensitive to MB, which is the well-known approved drug, even in the absence of light. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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13 pages, 3845 KiB

Open AccessArticle

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

by Zoia R. Korobova, Elena V. Zueva, Natalia A. Arsentieva, Oleg K. Batsunov, Natalia E. Liubimova, Irina V. Khamitova, Raisa N. Kuznetsova, Artem A. Rubinstein, Tikhon V. Savin, Oksana V. Stanevich, Alexandr N. Kulikov, Dmitry E. Pevtsov and Areg A. Totolian

Viruses 2022, 14(5), 941; https://doi.org/10.3390/v14050941 - 29 Apr 2022

Cited by 18 | Viewed by 3207

Abstract

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and [...] Read more.

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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14 pages, 7647 KiB

Open AccessArticle

Epidemiological Features of COVID-19 in Northwest Russia in 2021

by Anna Gladkikh, Vladimir Dedkov, Alena Sharova, Ekaterina Klyuchnikova, Valeriya Sbarzaglia, Olga Kanaeva, Tatyana Arbuzova, Nadezhda Tsyganova, Anna Popova, Edward Ramsay and Areg Totolian

Viruses 2022, 14(5), 931; https://doi.org/10.3390/v14050931 - 29 Apr 2022

Cited by 7 | Viewed by 2305 | Correction

Abstract

Appearing in Wuhan (China) and quickly spreading across the globe, the novel coronavirus infection quickly became a significant threat to global health. The year 2021 was characterized by both increases and decreases in COVID-19 incidence, and Russia was no exception. In this work, [...] Read more.

Appearing in Wuhan (China) and quickly spreading across the globe, the novel coronavirus infection quickly became a significant threat to global health. The year 2021 was characterized by both increases and decreases in COVID-19 incidence, and Russia was no exception. In this work, we describe regional features in the Northwestern federal district (FD) of Russia of the pandemic in 2021 based on Rospotrebnadzor statistics and data from SARS-CoV-2 genetic monitoring provided by the Saint Petersburg Pasteur Institute as a part of epidemiological surveillance. The epidemiological situation in the studied region was complicated by the presence of the megacity Saint Petersburg, featuring a high population density and its status as an international transport hub. COVID-19 incidence in the Northwestern FD fluctuated throughout the year, with two characteristic maxima in January and November. An analysis of fluctuations in the age structure, severity of morbidity, mortality rates, and the level of population vaccination in the region during the year is given. Assessment of epidemiological indicators was carried out in relation to changes in locally circulating genetic variants. It was seen that, during 2021, so-called variants of concern (VOC) circulated in the region (Alpha, Beta, Delta, Omicron), with Delta variant strains dominating from June to December. They successively replaced the variants of lines 20A and 20B circulating at the beginning of the year. An epidemiological feature of the northwestern region is the AT.1 variant, which was identified for the first time and later spread throughout the region and beyond its borders. Its share of the regional viral population reached 28.2% in May, and sporadic cases were observed until September. It has been shown that genetic variants of AT.1 lineages distributed in Russia and Northern Europe represent a single phylogenetic group at the base of the 20B branch on the global phylogenetic tree of SARS-CoV-2 strains. The progression of the COVID-19 pandemic occurred against the background of a vaccination campaign. The findings highlight the impact of vaccination on lowering severe COVID-19 case numbers and the mortality rate, despite ongoing changes in circulating SARS-CoV-2 genetic variants. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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17 pages, 1807 KiB

Open AccessArticle

TREC/KREC Levels and T and B Lymphocyte Subpopulations in COVID-19 Patients at Different Stages of the Disease

by Andrei A. Savchenko, Elena Tikhonova, Igor Kudryavtsev, Dmitry Kudlay, Ilya Korsunsky, Vasily Beleniuk and Alexandr Borisov

Viruses 2022, 14(3), 646; https://doi.org/10.3390/v14030646 - 21 Mar 2022

Cited by 21 | Viewed by 3553

Abstract

Background: T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets [...] Read more.

Background: T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets as well as KREC levels and B lymphocyte subsets. The aim of the present study was to evaluate the correlation between the TREC/KREC concentrations and T/B lymphocyte subsets at different stages of COVID-19. Methods: We examined 33 patients in the acute stage of COVID-19 (including 8 patients with poor outcomes) and 33 COVID-19 survivors. TREC/KREC concentrations were measured using quantitative real-time PCR. T/B lymphocyte subsets were determined using flow cytometry. Results: Blood TREC and KREC levels were found to be significantly lower in the acute stage of COVID-19 compared to control values. Moreover, a zero blood TREC level was a predictor of a poor disease outcome. Reductions in CD3⁺CD4⁺CD45RO⁻CD62L⁻ and CD3⁺CD8⁺CD45RO⁻CD62L⁻ T cell counts (as well as in the main fractions of B1 and B2 B cells) indicated a favorable outcome in COVID-19 patients in the acute stage of the disease. Decreased CD3⁺CD4⁺CD45RO⁻CD62L⁺ and CD3⁺CD8⁺CD45RO⁻CD62L⁺ T cell frequencies and increased CD3⁺CD8⁺CD45RO⁻CD62L⁻ cell counts were found to indicate a poor outcome in patients with acute COVID-19. These patients were also found to have increased B1 cell counts while demonstrating no changes in B2 cell counts. The levels of effector T cell subsets an naïve B cells were normal in COVID-19 survivors. The most pronounced correlations between TREC/KREC levels and T/B cell subsets counts were observed in COVID-19 survivors: there were positive correlations with naïve T and B lymphocytes and negative correlations with central and effector memory T cell subsets. Conclusions: The assessment of correlations between TREC and T cell subsets as well as KREC levels and B cell subset counts in patients with acute COVID-19 and COVID-19 survivors has shown that blood concentrations of TREC and KREC are sensitive indicators of the stage of antigen-independent differentiation of adaptive immunity cells. The results of the TREC and KREC analysis correlated with the stages of COVID-19 and differed depending on the outcome of COVID-19. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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Review

Jump to: Research, Other

23 pages, 982 KiB

Open AccessReview

Influenza B: Prospects for the Development of Cross-Protective Vaccines

by Liudmila M. Tsybalova, Liudmila A. Stepanova, Edward S. Ramsay and Andrey V. Vasin

Viruses 2022, 14(6), 1323; https://doi.org/10.3390/v14061323 - 17 Jun 2022

Cited by 11 | Viewed by 3452

Abstract

In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide [...] Read more.

In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide an overview of viral proteins as cross-protective vaccine targets, along with other updated broadly protective vaccine strategies. The importance of developing such vaccines lies not only in influenza B prevention, but also in the very attractive prospect of eradicating the influenza B virus in the human population. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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28 pages, 4474 KiB

Open AccessReview

Dysregulated Immune Responses in SARS-CoV-2-Infected Patients: A Comprehensive Overview

by Igor Kudryavtsev, Artem Rubinstein, Alexey Golovkin, Olga Kalinina, Kirill Vasilyev, Larisa Rudenko and Irina Isakova-Sivak

Viruses 2022, 14(5), 1082; https://doi.org/10.3390/v14051082 - 18 May 2022

Cited by 24 | Viewed by 4454

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in humans more than two years ago and caused an unprecedented socio-economic burden on all countries around the world. Since then, numerous studies have attempted to identify various mechanisms involved in the alterations [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in humans more than two years ago and caused an unprecedented socio-economic burden on all countries around the world. Since then, numerous studies have attempted to identify various mechanisms involved in the alterations of innate and adaptive immunity in COVID-19 patients, with the ultimate goal of finding ways to correct pathological changes and improve disease outcomes. State-of-the-art research methods made it possible to establish precise molecular mechanisms which the new virus uses to trigger multisystem inflammatory syndrome and evade host antiviral immune responses. In this review, we present a comprehensive analysis of published data that provide insight into pathological changes in T and B cell subsets and their phenotypes, accompanying the acute phase of the SARS-CoV-2 infection. This knowledge might help reveal new biomarkers that can be utilized to recognize case severity early as well as to provide additional objective information on the effective formation of SARS-CoV-2-specific immunity and predict long-term complications of COVID-19, including a large variety of symptoms termed the ‘post-COVID-19 syndrome’. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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Other

Jump to: Research, Review

1 pages, 161 KiB

Open AccessCorrection

Correction: Gladkikh et al. Epidemiological Features of COVID-19 in Northwest Russia in 2021. Viruses 2022, 14, 931

by Anna Gladkikh, Vladimir Dedkov, Alena Sharova, Ekaterina Klyuchnikova, Valeriya Sbarzaglia, Olga Kanaeva, Tatyana Arbuzova, Nadezhda Tsyganova, Anna Popova, Edward Ramsay and Areg Totolian

Viruses 2023, 15(5), 1190; https://doi.org/10.3390/v15051190 - 18 May 2023

Cited by 1 | Viewed by 1039

Abstract

There was an error in the original publication [...] Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

11 pages, 982 KiB

Open AccessBrief Report

Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests

by Alexandra Rak, Svetlana Donina, Yana Zabrodskaya, Larisa Rudenko and Irina Isakova-Sivak

Viruses 2022, 14(9), 2041; https://doi.org/10.3390/v14092041 - 14 Sep 2022

Cited by 21 | Viewed by 2537

Abstract

The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those [...] Read more.

The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccinated with specific vaccines has been characterized in numerous studies, mainly using Spike protein-based serology tests. However, Spike protein and specifically its receptor-binding domain (RBD) are mutation-prone, suggesting the reduced sensitivity of the validated serology tests in detecting antibodies raised to variants of concern (VOC). The viral nucleocapsid (N) protein is more conserved compared to Spike, but little is known about cross-reactivity of the N-specific antibodies between the ancestral B.1 virus and different VOCs. Here, we generated recombinant N phosphoproteins from different SARS-CoV-2 strains and analyzed the magnitude of N-specific antibodies in COVID-19 convalescent sera using an in-house N-based ELISA test system. We found a strong positive correlation in the magnitude of anti-N (B.1) antibodies and antibodies specific to various VOCs in COVID-19-recovered patients, suggesting that the N-binding antibodies are highly cross-reactive, and the most immunogenic epitopes within this protein are not under selective pressure. Overall, our study suggests that the RBD-based serology tests should be timely updated to reflect the constantly evolving nature of the SARS-CoV-2 Spike protein, whereas the validated N-based test systems can be used for the analysis of sera from COVID-19 patients regardless of the strain that caused the infection. Full article

(This article belongs to the Special Issue Viruses Research in Russia 2022)

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