Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Plausible reasons for the resurgence of Mpox (formerly Monkeypox): an overview.

Poxviruses are large and diversified viruses that cause an emerging zoonotic disease known as monkeypox (mpox). In the past, mpox predominated primarily in the rural rainforests of Central and West Africa. Recently, the exportation of mpoxv from Africa to other continents has been progressively reported. However, the lack of travel history to Africa in most of the currently reported cases in 2022 promotes the sign of changing epidemiology of this disease. Concerns over the geographic distribution and continued resurgence of mpox is growing. In this review, we addressed the geographic distribution, transmission, reasons for the resurgence of mpox, and vaccination. Although the precise cause of the resurgence in mpox cases is mostly unknown, several suggested factors are believed to be waning immunity, accumulation of unvaccinated people, ecological conditions, risk behaviors of men who have sex with men, and genetic evolution.

Characterization and immunogenicity of a novel chimeric hepatitis B core-virus like particles (cVLPs) carrying rotavirus VP8*protein in mice model.

Given the efficacy and safety issues of the WHO for approved/prequalified live attenuated rotavirus (RV) vaccines, studies on alternative non-replicating modals and proper RV antigens are actively undertaken. Herein, we report the novel chimeric hepatitis B core-virus like particles (VLPs) carrying RV VP8*26-231 protein of a P [8] strain (cVLPVP8*), as a parenteral VLP RV vaccine candidate. SDS-PAGE and Western blotting analyses indicated the expected size of the E. coli-derived HBc-VP8* protein that self-assembled to cVLPVP8* particles. Immunization in mice indicated development of higher levels of IgG and IgA as well as higher IgG1/IgG2a ratios by cVLPVP8* vaccination compared to the VP8* alone. Assessment of neutralizing antibodies (nAbs) indicated development of heterotypic nAbs with cross-reactivity to a heterotypic RV strain by cVLPVP8* immunization compared to VP8* alone. The observed anti-VP8* cross-reactivity might indicate the possibility of developing a Pan-genomic RVA vaccine based on the cVLPVP8* formulation that deserves further challenge studies.

Critical involvement of circular RNAs in virus-associated cancers.

Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV), Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus (HTLV), and Merkel cell polyomavirus (MCV)) that infect humans have been identified as an oncogene and have been associated with several human malignancies. Recently, growing attention has been attracted to exploring the pathogenesis of virus-related cancers. One of the most mysterious molecules involved in carcinogenesis and progression of virus-related cancers is circular RNAs (circRNA). These emerging non-coding RNAs (ncRNAs), due to the absence of 5' and 3' ends, have high stability than linear RNAs and are found in some species across the eukaryotic organisms. Compelling evidence has revealed that viruses also encode a repertoire of circRNAs, as well as dysregulation of these viral circRNAs play a critical role in the pathogenesis and progression of different types of virus-related cancers. Therefore, understanding the exact role and function of the virally encoded circRNAs with virus-associated cancers will open a new road for increasing our knowledge about the RNA world. Hence, in this review, we will focus on emerging roles of virus-encoded circRNAs in multiple cancers, including cervical cancer, gastric cancer, Merkel cell carcinoma, nasopharyngeal carcinoma, Kaposi cancer, and liver cancer.

The predominance of recombinant Norovirus GII.4Sydney[P16] strains in children less than 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022.

The present study was aimed to both detect emerging noroviruses and investigate RdRp and VP1-based dual typing of circulating noroviruses in hospitalized children less than 5 years of age with acute gastroenteritis (AGE) in Iran. For this purpose, a total of 200 stool specimens were screened during 2021-2022 by real-time RT-PCR for genogroup I and II (GI and GII) and dual-typed by sequence analysis of PCR products, using a web-based norovirus Typing Tool and phylogenetic analysis. The GI and GII noroviruses were detected in 20% of 200 specimens. The GII.4 norovirus was found to be the most common VP1 genotype (53%) followed by GII.8 (32%), GII.7 (6%), GII.17 (6%), and GII.3 (3%). The GII.P16 norovirus was also found as the predominant RdRp type (53%) followed by GII.P8 (32%), GII.P7 (6%), GII.P17 (6%), and GII.P31 (3%). To our knowledge, this is the first report that highlights the dominancy of recombinant norovirus GII.4Sydney[P16] and newly emerging of norovirus GII.8 [P8], GII.17 [P17] and GII.3 [P16] in Iran. These findings further indicate inter-genotype recombinant strains of noroviruses.

Molecular characterization of rotavirus infections in children less than 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022: Emergence of uncommon G9P[4] and G9P[8] rotavirus strains.

The present study was conducted to monitor the genotypes of circulating species A rotavirus (RVA) in Iran and investigate genetic linkages between specific RVA VP7, VP4, VP6, and NSP4 segments. For this purpose, 48 RVA strains were detected during the 2021-2022 seasons. The two combinations of G9P[4] and G9P[8] RVA strains were predominant. However, several other combinations of RVA also were detected. Based on the distribution of I and E genotypes (46 strains) with respect to G and P, the most common strains were G9P[4]-I2-E2 (19.5%), G9P[4]-I2-E1 (6.5%), G9P[4]-I1-E1 (4.3%), G9P[8]-I1-E1 (19.5%), and G9P[8]-I2-E2 (10.9%), which were followed by several other combinations of G and P RVA strains with different pattern of I-E genotypes and also emerging, rare and uncommon strains. The present study described the continued circulation of G9 strains with the emergence of uncommon G9P[4] and G9P[8] reassortants with three and two different I-E genotypes, respectively, which have not been reported previously in Iran. Our findings indicated that these uncommon strains exhibited a unique genotype pattern comprising a mixture of genogroup 1 and 2 genes and suggest the need for further analysis of rare, uncommon, and emerging strains of RVA at all 11 gene segments to determine intergenogroup and intragenotype reassortments.

Circulating rotavirus P[8]-lineage IV, unlike P[8]-lineage III, significantly related to nonsecretors status in Iranian children.

Rotavirus (RV) P[8] strains are responsible for the most of the RV infections globally and are significantly associated with the secretor and Lewis positive status. Among the distinct P[8] lineages, different ligand affinities have been detected which can be linked to differences in secretor status associated histo-blood group antigens (HBGAs). Herein, we report the lineages of P[8] strains and their associated secretor and Lewis antigen phenotypes in Iranian children. The phylogenetic tree and sequence analyses showed that the most common detected RV P[8] strain belonged to P[8]-lineage III (92%) and were significantly associated with secretor and Lewis positive status. In contrast, 8% of P[8] strains clustered into the P[8]-lineage IV and were significantly associated with nonsecretor status, implying that lineage IV tends to infect nonsecretor individuals. Furthermore, protein modeling and amino acid analyses of the VP8* glycan binding site of Iranian P[8]-lineage IV strains indicated two residual substitutions (T184V and N216V/I) compared to the P[8]-lineage III strains that might have affected the glycan affinity among P[8]-lineages IV strains. The corresponding residual changes might permit their continued transmission in nonsecretor children in competition with other P[8]-lineages. Although nonsecretors show natural resistant to P[8] strains, but such residual changes might overcome this natural resistance which in turn might indirectly contribute to the decline in the vaccine efficacy in populations where HBGA polymorphism allows their circulation at high frequency.

In vitro Effect of EBV Infection on HERV-K18 env Expression in the Presence and Absence of Vitamin D in Multiple Sclerosis Patients.

Background: HERV-K env is associated with several neurological disorders, including MS. Clinical studies have demonstrated a plausible interaction between HERV-K env and other MS risk factors. The present study aimed to investigate the possible association between HERV-K18 env and TGF-ß. We further assessed the in vitro effect of EBV infection on HERV-K18 env expression in the presence and absence of vitamin D in MS patients. Methods: PBMCs from 20 MS patients and 20 healthy controls were infected with the B95.8 EBV, seeded into 24-well plates and incubated in the presence or absence of 100 nM of 1,25(OH)D3. The expression levels of HERV-K18 env and TGF-ß were measured using real-time PCR. Results: While the expression level of HERV-K18 env was significantly higher in MS patients than the healthy controls, this trend for TGF-ß was significantly reverse. Interestingly, an inverse correlation was found between HERV-K18 env and TGF-ß expression in MS patients, although the in vitro stimulation of PBMCs with EBV and vitamin D showed no significant differences in terms of HERV-K18 expression. Conclusion: Our findings highlight the potential role of HERV-K18 env in MS patients.

Thrombotic storm in coronavirus disease 2019: from underlying mechanisms to its management.

Introduction. Coronavirus disease 2019 (COVID-19) identified in December 2019 in Wuhan, China, is associated with high mortality rates worldwide.Hypothesis/Gap Statement. Thrombotic problems, such as coagulopathy, are common in COVID-19 patients. Despite anticoagulation, thrombosis is more common in patients in the intensive care unit and patients with more severe disease. Although the exact mechanisms of coagulopathy in COVID-19 patients are still unclear, studies showed that overactivation of the renin-angiotensin system (RAS), cytokine storm, endothelial damage, formation of neutrophil extracellular traps (NETs), and also extracellular vesicles (EVs) in response to COVID-19 induced inflammation can lead to systemic coagulation and thrombosis.Aim. The management of COVID-19 patients requires the use of basic and readily available laboratory markers, both on admission and during hospitalization. Because it is critical to understand the pathophysiology of COVID-19 induced coagulopathy and treatment strategies, in this review we attempt to explain the underlying mechanism of COVID-19 coagulopathy, its diagnosis, and the associated successful treatment strategies.Conclusion. The exact mechanisms behind COVID-19-related coagulopathy are still unclear, but several studies revealed some mechanisms. More research is needed to determine the best anticoagulant regimen and to study other therapeutic options.

Genetic characterization of P[8] rotavirus strains circulated in Iran between 2009 and 2017.

Group A rotavirus (RVA) is the most common cause of acute gastroenteritis worldwide, which is responsible for causing an estimated 120 000 deaths in children under 5 years of age, which mostly occur in the lower-income countries of Asia and Africa. The G1P[8] is a common genotype of RVA that has spread throughout the world, including Iran and this genotype is present in two commonly used RVA vaccines, RotarixTM and RotaTeqTM . In this study, we investigated the genetic diversity, viral evolution, and differences between antigenic epitopes of Iran's P[8] strains and two licensed vaccines. The phylogenetic and evolutionary analysis was carried out, using MEGA version 6.0 and BEAST, respectively. Antigenic epitopes of VP8* were compared to determine the differences between strains from Iran and RotarixTM and RotaTeqTM . The P[8]-lineages III and IV were found as the predominant P genotype that circulated in Iran. The TMRCA of P[8]-lineages III and IV was estimated in 1987 and 2009, respectively. The P[8]-lineage III strains showed 12 amino acid changes compared to RotarixTM and 10 amino acid changes compared to RotaTeqTM . The P[8]-lineage IV strains showed 10 amino acid variations for both RotarixTM and RotaTeqTM strains. The results revealed that the P[8] strains circulating in Iran differ from RotarixTM and RotaTeqTM strains. To monitor the long-term effects of vaccines on the emergence of P[8] strains with different lineages, routine and successful monitoring of these strains will be crucial.

Rotavirus VP6: involvement in immunogenicity, adjuvant activity, and use as a vector for heterologous peptides, drug delivery, and production of nano-biomaterials.

The first-generation, live attenuated rotavirus (RV) vaccines, such as RotaTeq and Rotarix, were successful in reducing the number of RV-induced acute gastroenteritis (AGE) and child deaths globally. However, the low efficacy of these first-generation oral vaccines, coupled with safety concerns, required development of improved RV vaccines. The highly conserved structural protein VP6 is highly immunogenic, and it can generate self-assembled nano-sized structures, including tubes and spheres (virus-like particles; VLPs). Amongst the RV proteins, only VP6 shows these features. Interestingly, VP6-assembled structures, in addition to being highly immunogenic, have several other useful characteristics that could allow them to be used as adjuvants, immunological carriers, and drug-delivery vehicles as well as acting a scaffold for production of valuable nano-biomaterials. This review provides an overview of the self-assembled nano-sized structures of VP6-tubes/VLPs and their various functions.

The role of human endogenous retroviruses (HERVs) in Multiple Sclerosis and the plausible interplay between HERVs, Epstein-Barr virus infection, and vitamin D.

Multiple Sclerosis (MS) is one of the chronic inflammatory diseases with neurological disability in the central nervous system (CNS). Although the exact cause of MS is still largely unknown, both genetic and environmental factors are thought to play a role in disease risk. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. HERVs are normally silenced or expressed at low levels, although their expression is higher in MS than in the healthy population. Several studies highlighted the plausible interaction between HERVs and other MS risk factors, including viral infection like Epstein-Barr viruses and vitamin D deficiency which may lead to high expression of HERVs in these patients. Understanding how HERVs act in this scenario can improve our understanding towards MS etiology and may lead to the development of antiretroviral therapies in these patients. Here in this review, we try to examine the different HERVs expression implicated in MS and their association with EBV infection and vitamin D status.

Co-administration of rotavirus nanospheres VP6 and NSP4 proteins enhanced the anti-NSP4 humoral responses in immunized mice.

Inconveniences associated with the efficacy and safety of the World Health Organization (WHO) approved/prequalified live attenuated rotavirus (RV) vaccines, sounded for finding alternative non-replicating modals and proper RV antigens (Ags). Herein, we report the development of a RV candidate vaccine based on the combination of RV VP6 nanospheres (S) and NSP4112-175 proteins (VP6S + NSP4). Self-assembled VP6S protein was produced in insect cells. Analyses by western blotting and transmission electron microscopy (TEM) indicated expression of VP6 trimer structures with sizes of ≥140 kDa and presence of VP6S. Four group of mice were immunized (2-dose formulation) intra-peritoneally (IP) by either¨VP6S + NSP4¨ or each protein alone (VP6S or NSP4112-175) emulsified in aluminium hydroxide or control. Results indicated that VP6S + NSP4 formulation induced significant anti-VP6 IgG (P < 0.001) and IgA (P < 0.05) as well as anti-NSP4 IgG (P < 0.001) and enhancement of protective immunity. Analyses of anti-VP6S and anti-NSP4 IgG subclass (IgG1 and IgG2a) showed IgG1/IgG2a ≥6 and IgG1/IgG2a ≥3 ratios, respectively indicating Th2 polarization of immune responses. The combination of VP6S + NSP4 proteins emulsified in aluminum hydroxide adjuvant might present a dual universal, efficient and cost-effective candidate vaccine against RV infection.

The role of single-domain antibodies (or nanobodies) in SARS-CoV-2 neutralization.

The severe acute respiratory syndrome (SARS-CoV-2), a newly emerging of coronavirus, continues to infect humans in the absence of a viable treatment. Neutralizing antibodies that disrupt the interaction of RBD and ACE2 has been under the spotlight as a way of developing the COVID-19 treatment. Some animals, such as llamas, manufacture heavy-chain antibodies that have a single variable domain (VHH) instead of two variable domains (VH/VL) as opposed to typical antibodies. Nanobodies are antigen-specific, single-domain, changeable segments of camelid heavy chain-only antibodies that are recombinantly produced. These types of antibodies exhibit a wide range of strong physical and chemical properties, like high solubility, and stability. The VHH's high-affinity attachment to the receptor-binding domain (RBD) allowed the neutralization of SARS-CoV-2. To tackle COVID-19, some nanobodies are being developed against SARS-CoV-2, some of which have been recently included in clinical trials. Nanobody therapy may be useful in managing the COVID-19 pandemic as a potent and low-cost treatment. This paper describes the application of nanobodies as a new class of recombinant antibodies in COVID-19 treatment.

COVID-19 associated central nervous system manifestations, mental and neurological symptoms: a systematic review and meta-analysis.

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral infections can infect the nervous system; these viral infections can present a wide range of manifestation. The aim of the current study was to systematically review the COVID-19 associated central nervous system manifestations, mental and neurological symptoms. For that we conducted a comprehensive systematic literature review of four online databases, including Web of Science, PubMed, Scopus and Embase. All relevant articles that reported psychiatric/psychological symptoms or disorders in COVID-19 without considering time and language restrictions were assessed. All the study procedures were performed based on the PRISMA criteria. Due to the screening, 14 studies were included. The current study result indicated that, the pooled prevalence of CNS or mental associated disorders with 95% CI was 50.68% (6.68-93.88). The most prevalence symptoms were hyposmia/anosmia/olfactory dysfunction (number of study: 10) with 36.20% (14.99-60.51). Only one study reported numbness/paresthesia and dysphonia. Pooled prevalence of numbness/paresthesia and dysphonia was 5.83% (2.17-12.25) and 2.39% (10.75-14.22). The pooled prevalence of depression and anxiety was 3.52% (2.62-4.54) and 13.92% (9.44-19.08). Our findings demonstrate that COVID-19 has a certain relation with neurological symptoms. The hypsomia, anosmia or olfactory dysfunction was most frequent symptom. Other symptoms were headache or dizziness, dysgeusia or ageusia, dysphonia and fatigue. Depression, anxiety, and confusion were less frequent symptoms.

Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins.

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.

Critical review of Epstein-Barr virus microRNAs relation with EBV-associated gastric cancer.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is regarded as the most prevalent malignant tumor triggered by EBV infection. In recent years, increasing attention has been considered to recognize more about the disease process's exact mechanisms. There is accumulating evidence that showing epigenetic modifications play critical roles in the EBVaGC pathogenesis. MicroRNAs (miRNAs), as critical epigenetic modulators, are single-strand short noncoding RNA (length ~ <200 bp), which regulate gene expression through binding to the 3'-untranslated region (3'-UTR) of target RNA transcripts and either degrade or repress their activities. In the latest research on EBV, it was found that this virus could encode miRNAs. Mechanistically, EBV-encoded miRNAs are involved in carcinogenesis and the progression of EBV-associated malignancies. Moreover, these miRNAs implicated in immune evasion, identification of pattern recognition receptors, regulation of lymphocyte activation and lethality, modulation of infected host cell antigen, maintain of EBV infection status, promotion of cell proliferation, invasion and migration, and reduction of apoptosis. As good news, not only has recent data demonstrated the crucial function of EBV-encoded miRNAs in the pathogenesis of EBVaGC, but it has also been revealed that aberrant expression of exosomal miRNAs in EBVaGC has made them biomarkers for detection of EBVaGC. Regarding these substantial characterizes, the critical role of EBV-encoded miRNAs has been a hot topic in research. In this review, we will focus on the multiple mechanisms involved in EBVaGC caused by EBV-encoded miRNAs and briefly discuss their potential application in the clinic as a diagnostic biomarker.