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Rubella virus infection during pregnancy has several effects on the developing fetus. However, little is known about the epidemiology of the infection in Ethiopia. A cross-sectional study was conducted to assess the seroprevalence of rubella virus infection on consecutive 299 pregnant women attending antenatal care clinics in public health facilities in Halaba Town, Southern Ethiopia. Structured questionnaires were used to collect information on socio-demographic and reproductive characteristics. Venous blood samples were collected, and sera were tested for anti-rubella IgM and IgG using the enzyme-linked immunosorbent assay. Anti-rubella IgG and IgM were detected in 265 (88.6%) and 15 (5.0%) of 299 participants, respectively. Pregnant women in their first trimester [crude odds ratio (cOR) = 4.26; 95% CI (1.47, 12.4)] were at increased risk of having anti-rubella IgM compared to those in their second and third trimesters. Urban residents [cOR = 4.06; 95% CI (1.94, 8.47)] were with a higher percentage of IgG positivity compared to rural residents. Anti-rubella IgG positivity was higher in housewives [cOR = 2.94; 95% CI (1.07, 8.04)] compared to self-employed women. Our findings showed a high prevalence of rubella virus exposure, and considerable percentages of recent infection and susceptible women to contracting the infection, emphasizing the importance of congenital rubella syndrome in the research area. [ABSTRACT FROM AUTHOR]

Vertical transmission of rubella virus (RuV) occurs at a high rate during the first trimester of pregnancy. The modes of vertical transmission including the response of trophoblasts to RuV are not well understood. Here, RuV-trophoblast interaction was studied in the BeWo trophoblast cell line. Analysis included early and late time-point kinetics of virus infection rate and the antiviral innate immune response at mRNA and protein level. BeWo characteristics were addressed through metabolic activity by extracellular flux analysis and syncytiotrophoblast formation through incubation with forskolin. We found that RuV infection of BeWo led to profuse type III interferon (IFN) production. Transfecting trophoblast cells with dsRNA analog induced an increase in the production of type I IFN-β and type III IFNs; however, this did not occur in RuV-infected BeWo trophoblasts. IFN-β and to a lesser extent type III IFN-λ1 were inhibitory to RuV. While no significant metabolic alteration was detected, RuV infection reduced the cell number in the monolayer culture in comparison to the mock control and resulted in detached and floating cells. Syncytia formation restricted RuV infection. The use of BeWo as a relevant cell culture model for infection of trophoblasts highlights cytopathogenicity in the absence of a type I IFN response as a pathogenic alteration by RuV. [ABSTRACT FROM AUTHOR]

Here, we report a case of rubella virus-induced granulomatous dermatitis in a young girl with immunodeficiency caused by DCLRE1C gene mutations. The patient was a 6-year-old girl who presented with multiple erythematous plaques on the face and limbs. Biopsies of the lesions revealed tuberculoid necrotizing granulomas. No pathogens could be identified on extensive special stains, tissue cultures, or PCR-based microbiology assays. Metagenomic nextgeneration sequencing analysis revealed the rubella virus. Underlying atypical severe combined immunodeficiency was recognized based on the patient's history of repetitive infections since birth, low T-cell, B-cell, and NK cell counts, and abnormal immunoglobulins and complements. Whole-exome sequencing revealed the genetic abnormality of the atypical severe combined immunodeficiency (SCID), and compound heterozygous mutations of the DCLRE1C gene were detected. This report highlights the diagnostic values of metagenomic next-generation sequencing in identifying rare pathogens causing cutaneous granulomas in patients with atypical SCID. [ABSTRACT FROM AUTHOR]

Global efforts are underway to eliminate measles and rubella, and active viral surveillance is the key to achieving this goal. In addition, the World Health Organization announced guidelines for handling materials potentially infectious for poliovirus (PV) to minimize the risk of PV reintroduction and to achieve PV eradication. To support global efforts, we established new PV‐non‐susceptible cell lines that are useful for the isolation of measles virus (MeV) and rubella virus (RuV) (Vero ΔPVR1/2 hSLAM+). In the cell lines, MeV and RuV replicated efficiently, with no concern regarding PV replication. [ABSTRACT FROM AUTHOR]

To investigate viruses in measles‐negative cases, 221 measles‐suspected samples collected in Gyeonggi Province, South Korea were tested using a real‐time PCR assay. Rubella virus was not detected. However, 11 cases of parvovirus B19 (5.0%), 47 cases of human herpesvirus 6 (21.3%), 25 cases of human herpesvirus 7 (11.3%), and one case of co‐infection with parvovirus B19 and human herpesvirus 7 were confirmed, as were eight cases of co‐infection with human herpesvirus 6 and human herpesvirus 7. This study showed that parvovirus B19, human herpesvirus 6, and human herpesvirus 7 should be considered by physicians for the diagnosis of measles‐suspected patients. [ABSTRACT FROM AUTHOR]

Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10-3 subs/site/year and 8.9 x 10-4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.

PurposeNitazoxanide was recently reported as having in vitro effectiveness against the rubella virus. Immunodeficiency-related vaccine-derived rubella occurs in some patients who have an inherited immunodeficiency and who received the MMR vaccine. This study investigated the in vivo effectiveness of nitazoxanide therapy.MethodsThis is a retrospective analysis of seven patients treated with nitazoxanide as salvage therapy for immunodeficiency-related vaccine-derived rubella infection. The patients were recruited from an ongoing rubella detection surveillance project.ResultsSeven patients with persistent rubella were treated with nitazoxanide and one demonstrated significant clinical improvement. Two additional patients exhibited diminished viral capsid production with one patient having transient slowing of progression. The cohort overall generally had low T cell counts and had a high burden of comorbidities. There were three deaths. Two deaths were from PML and one was related to hematopoietic stem cell transplantation.ConclusionsNitazoxanide has limited in vivo anti-viral effects for immunodeficiency-related vaccine-derived rubella. Most patients did not exhibit clinical improvement.

Background: TORCH infections are the most common prenatal infections causing congenital malformation and infant mortality, especially in developing countries. Migrant women might be vulnerable to TORCH infections, but little is known about the association between migration-related characteristics and TORCH infection risk. This study aimed to investigate the impact of migrant status, migration distance, and the spouse's migrant status on the TORCH epidemic among women of childbearing age. Methods: Based on the National Free Preconception Health Examination Project, we analyzed a representative dataset of TORCH infections among women of childbearing age (15–49 years old) in Guangdong Province of China (2014–2019, n = 2,451,297). The past and/or recent infection status of TORCH infections (Toxoplasma gondii [TOX], Cytomegalovirus [CMV], and Rubella virus [RV]) were identified. Demographic and migration-related characteristics were collected. We thoroughly assessed the prevalence of TORCH infections in both migrant and native women and estimated adjusted odd ratios (aOR) for migration-related characteristics using multivariable logistic regression after adjusting the other sociodemographic factors. Results: Among all 2,451,297 participants, 443,725 (18.1%) were migrant women. Migrant women presented a lower risk of past TOX infection (aOR: 0.89, 0.88–0.91) suggesting a healthy migrant effect (HME), but a higher risk of recent TOX infection (aOR: 1.88, 1.77–1.99), past CMV infection (aOR: 1.26, 1.25–1.28) and RV infection in natural ways (aOR: 1.05, 1.04–1.06). Compared with intra-provincial migrants, inter-provincial migrants had a lower past TOX infection (aOR: 0.88, 0.85–0.91), but a higher risk of recent TOX infection (aOR: 1.16, 1.05–1.27) and RV infection (aOR: 1.33, 1.31–1.36). In addition, having a migrant spouse was associated with a higher risk for all types of infection. Conclusion: This study reported the association of migrant status and migration distance with TORCH infections, although the significance and directionality of these associations varied between pathogens. The spouse's migrant status further amplified the infection risk for all types of pathogens. Our findings suggested interventions for preventing the spread of CMV and RV infection and new acquisition of TOX infection for migrants in southern China, to narrow the native-migrant health inequity and decrease the incidence of prenatal infections and related adverse outcomes. [ABSTRACT FROM AUTHOR]

'Staggering disease' is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with'staggering disease' from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work indicates that RusV is the long-sought cause of feline 'staggering disease'. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans. Rustrela virus (RusV) was detected in the brains of 27 out of 29 domestic cats with 'staggering disease', but not of 29 control cats. This suggests RusV as the long-sought causative agent of 'staggering disease', which had been obscure for 50 years. [ABSTRACT FROM AUTHOR]

TORCH pathogens are a group of globally prevalent infectious agents that may cross the placental barrier, causing severe negative sequalae in neonates, including fetal death and lifelong morbidity. TORCH infections are classically defined by Toxoplasma gondii, other infectious causes of concern (e.g., syphilis, Zika virus, malaria, human immunodeficiency virus), rubella virus, cytomegalovirus, and herpes simplex viruses. Neonatal disorders and congenital birth defects are the leading causes of neonatal mortality in Central America's Northern Triangle, yet little is known about TORCH congenital syndrome in this region. This review synthesizes the little that is known regarding the most salient TORCH infections among pregnant women and neonates in Central America's Northern Triangle and highlights gaps in the literature that warrant further research. Due to the limited publicly available information, this review includes both peer-reviewed published literature and university professional degree theses. Further large-scale studies should be conducted to clarify the public health impact these infections in this world region. [ABSTRACT FROM AUTHOR]

Background: Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. Methods: One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. Results: One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. Conclusions: Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains. [ABSTRACT FROM AUTHOR]

Background: Rubella is a common inherited infection resulting in congenital cataracts and a significant cause of permanent vision loss in developing countries. In 2016, Indonesia had the highest number of congenital rubella syndrome (CRS) cases globally. Here, we report the first genotype of the rubella virus extracted from the eye lens from a child with congenital cataracts due to CRS. Case presentation: A female neonate was delivered by an elective caesarean delivery with normal birth weight at term from a 24-year-old mother in the rural setting. The baby presented with bilateral congenital cataracts, small-moderate secundum atrial septal defect, severe supravalvular pulmonary stenosis, and profound bilateral hearing loss. She also had microcephaly and splenomegaly. The patient's serology showed persistent positive IgG for rubella virus at the age of four years and four months. Following extraction during cataract surgery, viral detection of the lenses identified the presence of rubella. Phylogenetic analysis confirmed that the virus was grouped into genotype 1E. Conclusions: Our study reports the first phylogenetic analysis of the rubella virus extracted from the eye lens of a child with CRS in Indonesia. The detection of the rubella virus from eye lenses is remarkably promising. Our findings also emphasize the importance of molecular epidemiology in tracking the origin of rubella infection toward achieving virus eradication. [ABSTRACT FROM AUTHOR]

Introduction. Taking into account the particular importance of the assurance of the safety of antiviral vaccines containing, albeit attenuated, but live viruses, that can possibly retain the residual neurovirulence, it is important to develop additional tests to confirm the stability of attenuation using modern methods of laboratory diagnostics.The aim of the study was to assess the possibility of using the RT-PCR method as an additional test for monitoring the residual neurovirulence of attenuated rubella virus vaccine strains.Materials and methods. We used live attenuated vaccine strains of rubella virus "Orlov-V" and RA27/3. The study was carried out on 11 clinically healthy monkeys of the species Macaca mulatta weighing 3–5 kg, born and kept in the nursery of the Research Institute of Medical Primatology. The clinical material studied was tissue samples from various parts of the central nervous system (CNS), regional lymph nodes, parenchymal organs, plasma and cerebrospinal fluid of experimental animals. Control of extraneural dissemination of vaccine strains was carried out using virological (cytopathic action) and molecular biological methods (RT-PCR).Results. The absence of an infectious virus in the CNS, peripheral organs and blood plasma of monkeys infected with vaccine strains was demonstrated, which indicates a high level of attenuation of rubella virus strains "Orlov-B" and RA27/3. The analytical sensitivity of the RT-PCR method was found to exceed the analytical sensitivity of the cytopathic reaction by 1.7–3.3 lg when determining the content of rubella virus in the tissues of the CNS and peripheral organs of inoculated animals.Conclusion. Comparative analysis of experimental data showed that the detection of rubella virus by real-time PCR has a number of advantages due its specificity, sensitivity and a shorter turnaround time. In this connection, the RT-PCR method can be used as an additional test in the preclinical assessment of specific safety, namely, extraneural dissemination of attenuated vaccine strains, which is essential for quality and safety control of live rubella vaccines.

India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella. [ABSTRACT FROM AUTHOR]

The Rubella virus (RUBV) is a highly contagious pathogen classified within the rubivirus genus, primarily infecting humans and transmitted via airborne routes. RUBV infection generally manifests as a mild illness reminiscent of measles. However, when affecting pregnant women, it can lead to a severe condition known as congenital rubella syndrome (CRS). Rubella infection could be also associated with joint pain, arthritis, and neurological disorders. Determination of Rubella immunity and diagnosis conventionally involve the Hemagglutination Inhibition (HI) test or the Enzyme-Linked Immunosorbent Assay (ELISA). In this study, we describe the selection and characterization of specific aptamers targeting the Rubella virus by using the process of Systematic Evolution of Ligands by EXponantial enrichment (SELEX). The Binding affinity studies have shown that the two aptamers; R-7 and R-5 display the lowest dissociation constants (K d) of 6.58 nM and 19.05 nM, respectively. Then, R-7 aptamer was modified with a thiol group to enable its immobilization on screen-printed gold electrodes for the Rubella virus aptasensing. The label-free electrochemical detection was achieved using square wave voltammetry (SWV). The designed aptasensor has shown an excellent performance in detecting the Rubella virus within the range of 0.0005 ng/ml to 1000 ng/ml antigen and a limit of detection (LOD) of 0.00015 ng/ml. Selectivity studies were also performed against other viral antigens and serum proteins. Finally, the biosensor applicability was successfully demonstrated in spiked serum samples. [Display omitted] • Specific aptamers are selected and characterized for Rubella virus using SELEX. • High affinities were obtained; 6.58 nM and 19.05 nM. • Electrochemical aptasensor was developed for the detection of Rubella virus. • Wide linear range (0.0005 ng/ml to 1000 ng/ml) and LOD of 0.00015 ng/ml. • Good selectivity and applicability in serum samples. [ABSTRACT FROM AUTHOR]

Abstract Background Rubella virus (RV) is the causative agent of rubella or German measles. Although most infections cause only mild self-limited measles-like illness, the infection in pregnant women can cause severe foetal malformation or even miscarriage, especially in the first 3 months of pregnancy. Therefore, it is of great practical significance to establish a simple and sensitive RV detection method. Methods The partial epitopes of the E1 and E2 proteins from Rubella Virus were selected as the target sites, the sequence of the selected antigenic sites of the E1 and E2 were linked by a linker. The expression plasmid P6T was constructed by inserting the gene into PET-32A + with a histidine Tag. The P6 protein was induced and expressed in Escherichia coli L21 (DE3) and purified by nickel column affinity. The protein P6 antigen was identified by Western blotting analysis, and an anti-P6 antibody ELISA was established to test known serum samples to evaluate the capability of this method. Results After purification, the concentration and purity of the protein P6 were 0.283 mg/mL and more than 80%, respectively. Western blotting analysis showed that the protein P6 could react with rubella virus positive serum. By ELISA, 36 negative sera and 58 positive sera were detected. The coincidence rate, specificity and sensitivity of the ELISA were 86.2%, 88.89% and 84.48%, respectively. The P6 ELISA with a kappa coefficient of 0.715, P

In 2002, the WHO Regional Office for Europe developed the Strategic Program for the Prevention of Measles and Congenital Rubella Infections in the European Region, which was revised in 2004. As a result of the revision, an additional target was set to eliminate endemic rubella in the region by 2010. Rubella is a disease well controlled by vaccination that accounts for a theoretical potential to interrupt its global transmission. Since 2013, the Russian Federation has been implementing the National Rubella Elimination Program. Elimination criteria have been revised as the Program proceeds. Currently, the main criterion for rubella elimination is the absence of endemic (local) virus transmission for at least 36 months, which should be confirmed by molecular genetic research methods. In addition, in the Russian Federation, an incidence rate of less than 1 case per 1 million population is also used as one of the elimination criteria. Since 2013, due to a high (over 95%) coverage of preventive vaccinations a decrease in incidence rates and their stabilization at a level of less than 1 per 1 million population since 2014 state in favor of successfully implemented Program. Genetic monitoring of rubella virus strains circulating in human population noted the termination of endemic virus transmission. While implementing the Elimination Program, the prevailing virus genotypes that circulate in Russia were found to be genotypes 1E and 2B showing a global distribution. The data obtained after molecular genetic monitoring allowed to find that the strains isolated during this period belonged to different clusters accounting for in favor of being imported. Considering the above factors such as high vaccination coverage, low incidence rate and lack of endemic virus transmission, the 2017 WHO Committee on verification of measles and rubella elimination assigned the Russian Federation the status of a country that has achieved rubella elimination. The continuation of the phase of infection elimination is confirmed annually. This article presents the results on comprehensive assessment of rubella elimination status in the Russian Federation by specialists from the National Scientific and Methodological Center for Measles and Rubella and WHO EURO Moscow regional reference laboratory for measles and rubella based on 2019 epidemiological data and molecular genetic studies.

ABSTRACT The lipid composition of the host cell membrane is one of the key determinants of the entry of enveloped viruses into cells. To elucidate the detailed mechanisms behind the cell entry of rubella virus (RuV), one of the enveloped viruses, we searched for host factors involved in such entry by using CRISPR/Cas9 genome-wide knockout screening, and we found sphingomyelin synthase 1 (SMS1), encoded by the SGMS1 gene, as a candidate. RuV growth was strictly suppressed in SGMS1-knockout cells and was completely recovered by the overexpression of enzymatically active SMS1 and partially recovered by that of SMS2, another member of the SMS family, but not by that of enzymatically inactive SMS1. An entry assay using pseudotyped vesicular stomatitis virus possessing RuV envelope proteins revealed that sphingomyelin generated by SMSs is crucial for at least RuV entry. In SGMS1-knockout cells, lipid mixing between the RuV envelope membrane and the membrane of host cells occurred, but entry of the RuV genome from the viral particles into the cytoplasm was strongly inhibited. This indicates that sphingomyelin produced by SMSs is essential for the formation of membrane pores after hemifusion occurs during RuV entry. IMPORTANCE Infection with rubella virus during pregnancy causes congenital rubella syndrome in infants. Despite its importance in public health, the detailed mechanisms of rubella virus cell entry have only recently become somewhat clearer. The E1 protein of rubella virus is classified as a class II fusion protein based on its structural similarity, but it has the unique feature that its activity is dependent on calcium ion binding in the fusion loops. In this study, we found another unique feature, as cellular sphingomyelin plays a critical role in the penetration of the nucleocapsid into the cytoplasm after hemifusion by rubella virus. This provides important insight into the entry mechanism of rubella virus. This study also presents a model of hemifusion arrest during cell entry by an intact virus, providing a useful tool for analyzing membrane fusion, a biologically important phenomenon.

Nodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition.

Rubella is listed by the World Health Organization (WHO) as a disease that needs to be eliminated worldwide. The aim of this study was to understand the progress and challenges towards rubella elimination in Beijing, China, by analyzing molecular surveillance data combined with immunization and surveillance strategies as well as epidemiological data. With high immunization coverage under the 3-dose policy (8 months, 18 months, and 6 years) and supplementary immunization activities for the floating population, rubella incidence showed a downward trend since 2010, despite two epidemics that occurred in 2014–2015 and 2019. The reported rubella cases were generally concentrated in the age group of 15–34 years. Although citywide surveillance for congenital rubella syndrome (CRS) has been carried out since 2016, only one case has been confirmed by laboratory testing. Furthermore, molecular surveillance data showed that rubella viruses (RVs) circulating in Beijing during 2010–2020 were evidently heterogeneous; the domestic lineage 1E-L1 and multiple imported lineages, including 2B-L1, 1E-L2, and 2B-L2c, were identified in the last decade. Meanwhile, two lineage-related switches were determined, including the displacement of lineage 1E-L1 with lineage 2B-L1 around 2014 and the transition between lineage 2B-L1 and lineage 1E-L2 and 2B-L2c in 2018–2019. This RV transmission pattern was similar to that observed across the country, whereas lineages 1E-L1 and 2B-L2c were prevalent in Beijing for a shorter period. Overall, these results indicate the need to maintain routine immunization with rubella-containing vaccines, promote regular supplementary immunization activities, and enhance rubella and CRS surveillance even in order to accelerate rubella elimination in Beijing. Further, the existing immunization strategies must be optimized to further close the immunity gap. [ABSTRACT FROM AUTHOR]

Purpose: To compare iris affectation in cytomegalovirus anterior uveitis (CMVAU), rubella virus-associated uveitis (RVU), and healthy contralateral eyes, using swept-source anterior segment optical coherence tomography (SS-AS-OCT). Materials and methods: A comparative, transversal, retrospective study examining 60 eyes from 30 patients—18 eyes (17 patients) with CMVAU, 14 eyes (13 patients) with RVU, and 28 healthy eyes—was performed. Six-millimeter cross-sectional SS-AS-OCT B-scans were obtained in each iris quadrant. Images were exported to ImageJ®. Qualitative and quantitative analyses were done: stromal thickness (ST), smooth index (SI), and optical density (OD) of pigment epithelium. Comparisons between measurements and clinical-demographic parameters were performed using SPSS®. Results: Qualitative analysis showed extensive damage in iris stroma but was unable to differentiate between both uveitis. RVU eyes had a lower mean ST (315.72 μm ± 42.4) compared to those with CMVAU (348.6 μm ± 46) (p = 0.047) and a lower ST in the upper (338.9 μm ± 38.52)/(386.25 μm ± 47.2) (p = 0.005) and temporal (281.5 μm ± 57.3)/(326.43 μm ± 62.3) (p = 0.016) quadrants. Mean (0.94 ± 0.02)/(0.9 ± 0.03) (p = 0.001), temporal (0.94 ± 0.02)/(0.89 ± 0.03) (p < 0.001), and nasal SI (0.094 ± 0.02)/(0.9 ± 0.04) (p = 0.005) were higher in RVU. OD was similar in both uveitis. In healthy eyes, mean ST (376.8 μm ± 39.7) was higher and mean SI was lower (0.87 ± 0.04) than in RVU (p < 0.001) and CMVAU eyes (p = 0.032). Mean OD was higher in healthy eyes (911 ± 130) than in CMVAU eyes (800 ± 200) (p = 0.037). Conclusions: The quantitative analysis of the SS-AS-OCT iris images allows for the differentiation between healthy eyes and those with CMVAU and RVU, as well as between both uveitis. [ABSTRACT FROM AUTHOR]

We investigated the epidemiology of measles and rubella infections in Senegal based on data from twelve consecutive years of laboratory-based surveillance (2010–2021) and conducted phylogenetic analyses of circulating measles viruses. Sera from measles-suspected cases were collected and tested for measles and rubella-specific IgM antibodies using enzyme-linked immunosorbent assays (ELISA). Throat swabs were collected from patients with clinically diagnosed measles for confirmation by reverse-transcription polymerase chain reaction (RT-PCR) and viral genotyping. Among 8082 laboratory-tested specimens from measles-suspected cases, serological evidence of measles and rubella infection was confirmed in 1303/8082 (16.1%) and 465/6714 (6.9%), respectively. The incidence of rubella is now low—0.8 (95% CI 0.4–1.3) cases per million people in 2021—whereas progress towards measles pre-elimination targets (<1.0 case per million people per year) appears to have stalled; there were 10.8 (95% CI 9.3–12.5) cases per million people in 2021. Phylogenetic analyses revealed that all Senegalese measles strains belonged to genotype B3. The rubella virus sequence obtained in this study was consistent with genotype 1C. Our national surveillance data suggest that despite their low incidence both measles and rubella remain endemic in Senegal with a concerning stagnation in the decline of measles infections that represents a significant challenge to the goal of regional elimination. [ABSTRACT FROM AUTHOR]

The Zika virus (ZIKV) is well known for causing congenital Zika syndrome if the infection occurs during pregnancy; however, the mechanism by which the virus infects and crosses the placenta barrier has not been completely understood. In pregnancy, TGF-β1 is abundant at the maternal–fetal interface. TGF-β1 has been reported to enhance rubella virus binding and infection in human lung epithelial cells. Therefore, in this study, we investigate the role of TGF-β1 in ZIKV infection in the immortalized human first-trimester trophoblasts, i.e., Swan.71. The cells were treated with TGF-β1 (10 ng/mL) for two days before being inoculated with the virus (American strain PRVABC59) at a multiplicity of infection of five. The results showed an enhancement of ZIKV infection, as demonstrated by the immunofluorescent assay and flow cytometry analysis. Such enhanced infection effects were abolished using SB431542 or SB525334, inhibitors of the TGF-β/Smad signaling pathway. An approximately 2-fold increase in the virus binding to the studied trophoblasts was found. In the presence of the Smad inhibitors, virus replication was significantly suppressed. An enhancement in Tyro3 and AXL (receptors for ZIKV) expression induced by TGF-β1 was also noted. The results suggest that TGF-β1 promotes the virus infection via the Smad pathway. Further studies should be carried out to clarify the underlying mechanisms of these findings. [ABSTRACT FROM AUTHOR]

Anterior uveitis has various causes, but the majority of cases are viral induced. The most common viral anterior uveitis etiology includes double-stranded DNA viruses of the Herpesviridae family, including Alpha herpes virinae (herpes simplex 1 and 2 and varicella zoster virus), Beta herpesvirinae (cytomegalovirus), and less frequently, Gamma herpesvirinae (Epstein-Barr virus). In the last few decades, a growing body of evidence has correlated Fuchs uveitis etiology to the rubella virus from the Matonaviridae family, which has a single-stranded RNA genome. The clinical presentation of each of these uveitis is hypertensive granulomatous anterior uveitis; however, the very slight differences between them, which often overlap, make differential diagnosis sometimes difficult. Therefore, diagnostic laboratory tests such as polymerase chain reaction and antibody index or Goldmann-Witmer coefficient analyses on the aqueous humor help to identify the etiology in doubtful cases and thus to plan targeted treatment. [ABSTRACT FROM AUTHOR]

The type I interferon (IFN) response is one of the primary defense systems against various pathogens. Although rubella virus (RuV) infection is known to cause dysfunction of various organs and systems, including the central nervous system, little is known about how human neural cells evoke protective immunity against RuV infection, leading to controlling RuV replication. Using cultured human neural cells experimentally infected with RuV RA27/3 strain, we characterized the type I IFN immune response against the virus. RuV infected cultured human neural cell lines and induced IFN-β production, leading to the activation of signal transducer and activator of transcription 1 (STAT1) and the increased expression of IFN-stimulated genes (ISGs). Melanoma-differentiation-associated gene 5 (MDA5), one of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors, is required for the RuV-triggered IFN-β mRNA induction in U373MG cells. We also showed that upregulation of RuV-triggered ISGs was attenuated by blocking IFN-α/β receptor subunit 2 (IFNAR2) using an IFNAR2-specific neutralizing antibody or by repressing mitochondrial antiviral signaling protein (MAVS) expression using MAVS-targeting short hairpin RNA (shRNA). Furthermore, treating RuV-infected cells with BX-795, a TANK-binding kinase 1 (TBK1)/I kappa B kinase ε (IKKε) inhibitor, robustly reduced STAT1 phosphorylation and expression of ISGs, enhancing viral gene expression and infectious virion production. Overall, our findings suggest that the RuV-triggered type I IFN-mediated antiviral response is essential in controlling RuV gene expression and viral replication in human neural cells. [ABSTRACT FROM AUTHOR]

Rubella virus (RuV) is an enveloped virus that usually causes mild disease in children, but can produce miscarriage or severe congenital birth defects. While in nature RuV only infects humans, the discovery of the related Ruhugu (RuhV) and Rustrela (RusV) viruses highlights the spillover potential of mammalian rubiviruses to humans. RuV buds into the Golgi, but its assembly and exit are not well understood. We identified a potential late domain motif 278 PPAY 281 at the C-terminus of the RuV E2 envelope protein. Such late domain motifs can promote virus budding by recruiting the cellular ESCRT machinery. An E2 Y281A mutation reduced infectious virus production by >3 logs and inhibited virus particle production. However, RuV was insensitive to inhibition by dominant-negative VPS4, and thus appeared ESCRT-independent. The E2 Y281A mutation did not significantly inhibit the production of the viral structural proteins capsid (Cp), E2, and E1, or dimerization, glycosylation, Golgi transport, and colocalization of E2 and E1. However, E2 Y281A significantly reduced glycoprotein-Cp colocalization and interaction, and inhibited Cp localization to the Golgi. Revertants of the E2 Y281A mutant contained an E2 281V substitution or the second site mutations [E2 N277I + Cp D215A]. These mutations promoted virus growth, particle production, E2/Cp colocalization and Cp-Golgi localization. Both the E2 substitutions 281V and 277I were found at the corresponding positions in the RuhV E2 protein. Taken together, our data identify a key interaction of the RuV E2 endodomain with the Cp during RuV biogenesis, and support the close evolutionary relationship between human and animal rubiviruses., Importance: Rubella virus (RuV) is an enveloped virus that only infects humans, where transplacental infection can cause miscarriage or congenital birth defects. We identified a potential late domain, 278 PPAY 281 , at the C terminus of the E2 envelope protein. However, rather than this domain recruiting the cellular ESCRT machinery as predicted, our data indicate that E2 Y281 promotes a critical interaction of the E2 endodomain with the capsid protein, leading to capsid's localization to the Golgi where virus budding occurs. Revertant analysis demonstrated that two substitutions on the E2 protein could partially rescue virus growth and Cp-Golgi localization. Both residues were found at the corresponding positions in Ruhugu virus E2, supporting the close evolutionary relationship between RuV and Ruhugu virus, a recently discovered rubivirus from bats., Competing Interests: The authors declare no conflict of interest.

Introduction: rubella poses a significant public health threat, particularly in developing countries, where congenital rubella remains a preventable concern. This cross-sectional study examined rubella seroprevalence among children aged 10 and under from May to September 2016 in Jos, Nigeria., Methods: using a multistage sampling method, eligible participants who had not been vaccinated against the rubella virus and consented to participate in the study were recruited across schools in the city. Rubella-specific IgG and IgM antibodies were detected from eluted serum collected from the participants using the enzyme-linked immunosorbent assay (ELISA). Data analysis and visualization was done using the R software version 4.3.1., Results: of the 405 participants investigated in this study, 336 (82.96%) tested positive for rubella IgG, while 9 (2.22%) tested positive for rubella IgM. Factors such as age ≥ 5 years and lack of Western education showed significant associations with rubella seropositivity., Conclusion: this study highlights the seroprevalence of rubella IgG and IgM antibodies among children aged 10 and under in Jos, Nigeria. The significant associations between rubella seropositivity and factors such as age ≥ 5 years and lack of Western education underscore the necessity for an effective rubella vaccination program to prevent congenital rubella syndrome (CRS)., Competing Interests: The authors declare no competing interests., (Copyright: Hyelshilni Samuel Waziri et al.)

Interferon lambda (IFN-λ, type III IFN, IL-28/29) is a family of antiviral cytokines that are especially important at barrier sites, including the maternal-fetal interface. Recent discoveries have identified important roles for IFN-λ during pregnancy, particularly in the context of congenital infections. Here, we provide a comprehensive review of the activity of IFN-λ at the maternal-fetal interface, highlighting cell types that produce and respond to IFN-λ in the placenta, decidua, and endometrium. Further, we discuss the role of IFN-λ during infections with congenital pathogens including Zika virus, human cytomegalovirus, rubella virus, and Listeria monocytogenes . We discuss advances in experimental models that can be used to fill important knowledge gaps about IFN-λ-mediated immunity.

Objective: The objective of this article is to report a rare case of glucocorticoid hypersensitivity syndrome, which may be associated with an underlying rubella virus infection. Case Report: A 29-year-old man showed progressive weight gain for 16 months accompanied by a moon face, enlarged dorsocervical fat pad, central obesity, and purple striae. His cortisol circadian rhythm was normal, and plasma cortisol levels at 8:00 AM fluctuated between 3.2 and 9.54 μg/dL (reference range, 4.3-22.4 μg/dL). A dexamethasone suppression test with a very low dose (0.25 mg) of dexamethasone showed a marked decrease in plasma cortisol level to 0 μg/dL. Adrenal computed tomography and pituitary magnetic resonance imaging findings were normal. The Z-score of the bone density in the lumbar spine was −4.2. The IgM antibody for the rubella virus was positive. His erythrocyte sedimentation rate was 24 mm/hour (reference range,

Rubella is a contagious disease caused by rubella virus leading to adverse outcomes among pregnant women including abortions, low birth weight, stillbirths and congenital rubella syndrome (CRS) in the baby. If not pregnant, the clinical manifestations are mild and self-limiting. In this hospital based cross-sectional study, 1985 blood samples were collected from females attending outpatient services of various hospitals to serologically detect Rubella infection. Rubella antibodies namely Immunoglobulin M (IgM)/Immunoglobulin G (IgG) were detected through enzyme linked immunosorbent assay (ELISA) or by identifying virus through polymerase chain reaction (PCR). From the total enrolled participants, 1951 samples were tested with age ranging from 16 to 38 years. Among the positive samples, about 60% patients had IgG antibodies as compared to less than 1% IgM and 0.40% by PCR. Out of 1951 samples, 7/849 (0.82%) and 651/1070 (60.8%) had IgM & IgG rubella antibodies respectively. The odds of having abortion was [OR-13.14 (4.94–34.97)] among anti-rubella positive and primi-gravida [OR-43.6 (5.9–322)] women. Therefore, vaccination of women against rubella before planning of pregnancy or at adolescence seems to be the need of hour to avoid the ill consequences during pregnancy as well as for the new born baby.

Objectives: Rubella cases in the Central African Republic (CAF) are currently identified during measles surveillance. This study aimed to investigate rubella epidemiology between 2015 and 2016 and to provide baseline genotype data for monitoring future rubella control efforts.Methods: 831 measles IgM negative or equivocal sera from 2015/2016 were tested for rubella IgM antibodies and 350 rubella IgM positive sera collected between 2008 and 2016 were selected for PCR and sequencing.Results: 411 of the 831 sera (49.5%) were rubella IgM positive and most cases (n=391, 95.1%) occurred between January and April. Most patients were between 5 and 9 years old (50.2%) and more than half of the rubella cases (56.7%) originated from the capital Bangui. Genotype information was obtained for 37 of the 350 selected rubella IgM-positive specimens, with the majority of the patients originating from Bangui (n=24, 64.9%) and sequences covering all years except 2009. Phylogenetic analysis identified genotypes 1E (n=12), 1G (n=5) and 2B (n=20), with 2B being detected from 2014 onwards.Conclusions: Our study confirmed the important role of rubella as a rash and fever disease in CAF and provided comprehensive data on rubella epidemiology and the first information on rubella genotypes in the country.

Objective: To assess the rate of positivity of Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (TORCH) pathogens in patients suffering from congenital cataract in Pakistan. Study Design: Cross sectional comparative study. Place and Duration of Study: Armed Forces Institute of Ophthalmology, Rawalpindi, from Jun 2017 to Mar 2018. Methodology: Cataract group included sixty children already diagnosed with congenital cataract and control group included 60 children not suffering from congenital cataract. Serum samples of all children were collected to test against IgG and IgM antibodies of Toxoplasma gondii, Rubella, Cytomegalo, Herpes simplex pathogens using enzyme linked immune essay (ELISA) technique. Data were analyzed observe in difference between unilateral and bilateral cataract and between cataract and control group. Results: Out of 60 children in cataract group, 29 were tested positive for Toxoplasma gondii, Rubella, Cytomegalo (CMV), Herpes simplex infections. CMV IgG antibodies were identified in 21 (35%) children followed by Rubella IgG 13 (21.7%), Toxoplasmosis IgG 8 (13.3%), CMV IgM 7 (11.7%), HSV I IgG 5 (8.3%), HSV II IgG 2 (3.3%) and HSV I IgM 1 (1.7%) antibodies. None of the children was positive for Toxoplasmosis, Rubella and HSV II IgM antibodies. There was no statistical difference in rate of positivity of Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex pathogens between unilateral and bilateral cataract and between cataract and control group. Conclusion: Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex pathogens are an important cause of congenital cataract with Cytomegalovirus and Rubella virus being most common respectively. In order to prevent paediatric complications, we need........

The World Health Organization has strict rules and recommendations on the selection and use of cell substrates in laboratories. Given the widespread use of safe and secure cell substrates in the production and quality control of viral vaccines and also the high demand for vaccines against viral diseases, obligating the selection of a suitable cell substrate for cultivation and production of biological products. Animal cell lines play a valuable role in the preparation and propagation of viral seeds; thus, the current study used the BHK-21 cell line among others for viral checking with the aim of replacing the BHK-21 C5 cell line with the RK13 cell line to investigate the cytopathic effects of the rubella virus. To this end, attempts were made to determine the characteristics of the BHK-21 C5 cell line including cell growth characteristics and sterility tests to validate its safety and security. Then, by culturing the cells in a 96-well microplate, titration of the rubella virus was subsequently performed by preparing serial dilutions of the virus from 10-1 to 10-5 and inoculated to cell lines in order to compare the sensitivity of BHK-21 C5 and RK13 cell lines to rubella virus. Data analysis according to the results of the tests by ahead default, p-value < 0/05 was equal to p-value = 0.01 based on SPSS analysis with the paired-sample t-test. In addition, the box-plot diagram indicated a significant difference between these cell lines. Based on the results, the BHK-21 C5 cell line seems to be more sensitive to the rubella virus than others. Therefore, it can be used for production and quality control of the vaccine and in research and diagnosis of rubella.

A growing number of organisations, including medical associations, recommend that research subjects should be given the option of being informed about the general outcome and results of the study. We recently completed a study involving nine serosurveys from 2018 to 2020 in five districts of India among three age groups (children 9 months to < 5 years; 5 to < 15 years of age, and women 15 to < 50 years of age before and after the measles and rubella (MR) vaccination campaigns). In Palghar district of Maharashtra all individuals in 30 selected clusters were enumerated, and 13 individuals per age group were randomly sampled. We established the procedures to return the results to the respondents for each stage of the survey. Of the 1,166 individuals selected for the measles and rubella serosurvey, 971 (83%) agreed to participate and were enrolled. Participants were informed that they will only be contacted if they test seronegative for measles and/or rubella antibodies. Overall, 140 individuals enrolled in the survey tested seronegative for IgG antibodies to measles and/or rubella viruses; were provided the reports and informed to seek medical advice. Upon follow up by phone, 10% (14) of the 140 participants reported to have been vaccinated. In this paper we discuss the procedures, experiences and considerations in returning results to participants in a community-based measles and rubella serosurvey. Although the lessons learned are specific to post measles-rubella vaccine campaign serosurvey in India, they might be helpful to those contemplating sharing results to participants of large scale survey settings. [ABSTRACT FROM AUTHOR]

Rubella, a viral disease characterized by a red skin rash, is well controlled because of an effective vaccine, but outbreaks are still occurring in the absence of available antiviral treatments. The Rubella virus (RUBV) papain-like protease (Rub- Pro) is crucial for RUBV replication, cleaving the nonstructural polyprotein p200 into two multifunctional proteins, p150 and p90. This protease could represent a potential drug target, but structural and mechanistic details important for the inhibition of this enzyme are unclear. Here, we report a novel crystal structure of RubPro at a resolution of 1.64 Å. The RubPro adopts a unique papain-like protease fold, with a similar catalytic core to that of proteases from Severe acute respiratory syndrome coronavirus 2 and foot-and-mouth disease virus while having a distinctive N-terminal fingers domain. RubPro has well-conserved sequence motifs that are also found in its newly discovered Rubivirus relatives. In addition, we show that the RubPro construct has protease activity in trans against a construct of RUBV protease-helicase and fluorogenic peptides. A protease-helicase construct, exogenously expressed in Escherichia coli, was also cleaved at the p150-p90 cleavage junction, demonstrating protease activity of the protease- helicase protein. We also demonstrate that RubPro possesses deubiquitylation activity, suggesting a potential role of RubPro in modulating the host's innate immune responses. We anticipate that these structural and functional insights of RubPro will advance our current understanding of its function and help facilitate more structure-based research into the RUBV replication machinery, in hopes of developing antiviral therapeutics against RUBV. [ABSTRACT FROM AUTHOR]

Rubella virus (RV) infection in susceptible women during the first trimester of pregnancy is associated with congenital Rubella syndrome (CRS). In countries where a vaccination program is implemented, active case surveillance is emphasized. This report documents the magnitude of active cases before and after vaccine implementation in Tanzania. A total of 8750 children and adolescents with signs and symptoms of RV infection were tested for Rubella IgM antibodies between 2013 and 2019 using enzyme immunoassay followed by descriptive analysis. The median age of participants was 3.8 (IQR: 2–6.4) years. About half (4867; 55.6%) of the participants were aged 1–5 years. The prevalence of RV active cases was 534 (32.6%, 95% CI: 30.2–34.9) and 219 (3.2%, 95% CI: 2.7–3.6) before and after vaccine implementation, respectively. Before vaccination, the highest prevalence was recorded in Pemba (78.6%) and the lowest was reported in Geita (15.6%), whereas, after vaccination, the prevalence ranged between 0.5% in Iringa and 6.5% in Pemba. Overall, >50% of the regions had a >90% reduction in active cases. The significant reduction in active cases after vaccine implementation in Tanzania underscores the need to sustain high vaccination coverage to prevent active infections and eventually eliminate CRS, which is the main goal of Rubella vaccine implementation. [ABSTRACT FROM AUTHOR]

Background and Objectives: A cross-sectional single-center study was conducted to investigate the etiology in hypertensive anterior uveitis whose clinical features are not fully distinctive from cytomegalovirus or from rubella virus and to demonstrate the possible coexistence of both these viruses in causing anterior uveitis. Materials and Methods: The clinical charts of a cohort of patients with hypertensive viral anterior uveitis of uncertain origin consecutively seen in a single center from 2019 to 2022 were retrospectively reviewed; data on the clinical features, aqueous polymerase chain reaction, and antibody response to cytomegalovirus and rubella virus were collected. Results: Forty-three eyes of as many subjects with viral anterior uveitis of uncertain origin were included. Thirty-two patients had an aqueous polymerase chain reaction or antibody index positive to cytomegalovirus only, while 11 cases had an aqueous antibody response to both cytomegalovirus and rubella virus. This latter overlapping group had a statistically significant higher rate of hypochromia and anterior vitritis (p-value: 0.02 and < 0.001, respectively). Conclusions: The simultaneous presence of intraocular antibodies against cytomegalovirus and rubella virus could redefine the differential diagnosis of hypertensive viral anterior uveitis, demonstrating a possible "converged" immune pathway consisting in a variety of stimuli. [ABSTRACT FROM AUTHOR]

To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018–9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide. [ABSTRACT FROM AUTHOR]

Mumps and rubella are vaccine-preventable viral diseases through the measles-mumps-rubella-varicella (MMRV) vaccine, administered at 12 months and again at 6 years. We assessed the sero-prevalence of mumps and rubella, identified factors associated with sero-negativity, and evaluated concordance between mumps and rubella sero-positivity. A national cross-sectional sero-survey was conducted on samples collected in 2015 by the Israel National Sera Bank. Samples were tested for mumps and rubella IgG antibodies using an enzyme-linked immunosorbent assay. Of 3131 samples tested for mumps IgG, 84.8% (95%CI: 83.5–86.0%) were sero-positive. Sero-negativity for mumps was significantly associated with age (high odds ratios observed in infants younger than 4 years and 20–29 years old subjects). Of 3169 samples tested for rubella IgG antibodies, 95.2% (95%CI: 94.4–95.9%) were sero-positive. Rubella sero-negativity was significantly associated with age (high odds ratios observed in children younger than 4 years old and adults older than 30 years), males, Jews, and others. Concordant sero-positivity for both mumps and rubella viruses was observed in 83.9% of the tested samples. The Israeli population was sufficiently protected against rubella but not against mumps. Since both components are administered in the MMRV vaccine simultaneously, the mumps component has a lower uptake than rubella and quicker waning. [ABSTRACT FROM AUTHOR]

Maintaining herd immunity against the rubella virus is important for controlling the spread and recurrence of rubella. Rubella vaccination for children has been affordable in Saudi Arabia since 1982. To assess the immune response derived from vaccination, we assessed the seroprevalence against the rubella virus among the population of the Madinah region. An indirect enzyme-linked immunosorbent assay (ELISA) was used to measure anti-rubella IgG antibodies in 791 serum samples obtained from 336 (42.5%) men and 455 (57.5%) women, ranging from 14 to 49 years in age. Among all participants, 94.2% were seropositive for rubella IgG antibodies, indicating a high degree of immunization. However, 5.8% of participants were seronegative, suggesting a population of either poor vaccine responders or the potential risk of waning vaccine-induced immunity. No significant difference or association with rubella seropositivity was identified according to age, sex, or pregnancy status. The median anti-rubella IgG antibody concentrations differed significantly between age groups (p < 0.001). Although a high percentage of the tested population in Madinah demonstrated anti-rubella IgG antibody seropositivity, a notable percentage of the population were seronegative, making them susceptible to infection. [ABSTRACT FROM AUTHOR]

We recently published an article about myelin oligodendrocyte glycoprotein-independent rubella infection of keratinocytes in vitro, in which first-trimester trophoblast cells were shown as rubella virus (RuV)-resistant. Given an incident rate as high as 90% of congenital rubella syndrome in the first eight weeks of pregnancy, the RuV infection of first-trimester trophoblasts is considered key to opening the gate to transplacental transmission mechanisms. Therefore, with this study, we aimed to verify the susceptibility/resistance of first-trimester trophoblast cell lines, HTR-8/SVneo and Swan.71, against RuV. Cells cultured on multi-well plates were challenged with a RuV clinical strain at a multiplicity of infection from 5 to 10 for 3 h. The infectivity was investigated by immunofluorescence (IF) assay and flow cytometry (FCM) analysis. Supernatants collected during the post-infection period were used to determine virus-progeny production. The scattered signaling of RuV infection of these cells was noted by IF assay, and the FCM analysis showed an average of 4–5% of gated cells infected with RuV. In addition, a small but significant production of virus progeny was also observed. In conclusion, by employing appropriate approaches, we determined the low infectivity of RuV in first-trimester trophoblast cell lines but not resistance as in our previous report. [ABSTRACT FROM AUTHOR]

Enhanced replication of rubella virus (RuV) and replicons by de novo synthesized viral structural proteins has been previously described. Such enhancement can occur by viral capsid proteins (CP) alone in trans. It is not clear whether the CP in the virus particles, i.e., the exogenous CP, modulate viral genome replication. In this study, we found that exogenous RuV CP also enhanced viral genome replication, either when used to package replicons or when mixed with RNA during transfection. We demonstrated that CP does not affect the translation efficiency from genomic (gRNA) or subgenomic RNA (sgRNA), the intracellular distribution of the non-structural proteins (NSP), or sgRNA synthesis. Significantly active RNA replication was observed in transfections supplemented with recombinant CP (rCP), which was supported by accumulated genomic negative-strand RNA. rCP was found to restore replication of a few mutants in NSP but failed to fully restore replicons known to have defects in the positive-strand RNA synthesis. By monitoring the amount of RuV RNA following transfection, we found that all RuV replicon RNAs were well-retained in the presence of rCP within 24 h of post-transfection, compared to non-RuV RNA. These results suggest that the exogenous RuV CP increases efficiency of early viral genome replication by modulating the stage(s) prior to and/or at the initiation of negative-strand RNA synthesis, possibly through a general mechanism such as protecting viral RNA. [ABSTRACT FROM AUTHOR]