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The Journal of Infectious Diseases Sep 2021In 2019, the United States (US) experienced the highest number of measles importations and cases in the postelimination era. More than a quarter of imported cases...
In 2019, the United States (US) experienced the highest number of measles importations and cases in the postelimination era. More than a quarter of imported cases entered the US through California. Measles surveillance efforts in California resulted in the identification of 26 importations, 6 outbreaks, and 72 cases in 2019. Only genotype B3 and D8 measles strains were detected. Genotype-specific differences were noted in the incidence of vaccine failures, hospitalizations, and severe complications among cases. A targeted whole genome sequencing approach provided higher-resolution discrimination between epidemiologically linked and sporadically introduced strains than conventional N450 sequencing. Our report underscores the importance of ensuring appropriate measles vaccination status, especially prior to international travel to measles-endemic regions, and highlights the value of a strong measles surveillance system in minimizing outbreaks and preserving measles elimination status in the US.
Topics: Adolescent; Adult; Aged; California; Child; DNA-Directed RNA Polymerases; Disease Outbreaks; Female; Genotype; Humans; Male; Measles; Measles Vaccine; Measles virus; Middle Aged; Molecular Epidemiology; Phylogeny; Sequence Analysis, DNA; United States; Young Adult
PubMed: 33528506
DOI: 10.1093/infdis/jiab059 -
Science (New York, N.Y.) Jun 2024An intermediate virus-cell fusion step is revealed by an antibody with therapeutic potential.
An intermediate virus-cell fusion step is revealed by an antibody with therapeutic potential.
Topics: Animals; Humans; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Measles; Measles virus; Virus Internalization
PubMed: 38935737
DOI: 10.1126/science.adq3348 -
Biologicals : Journal of the... Sep 2022Canine morbillivirus is a highly contagious multi-host pathogen with high morbidity and mortality. Timely diagnosis is of utmost importance to effectively control such a...
Canine morbillivirus is a highly contagious multi-host pathogen with high morbidity and mortality. Timely diagnosis is of utmost importance to effectively control such a dreadful disease. Monoclonal antibodies (mAbs) serve as a high throughput diagnostics and applied tools for research and development (R&D). In the present study, a total of six mouse monoclonal antibodies were developed. All the mAbs generated belonged to IgG class. Of the six mAbs, two of them, namely CD-2F8 and CD-3D8 were directed against the nucleocapsid protein of CDV as determined in western blotting. The reactivity of all the mAbs was checked in indirect-ELISA and cell-ELISA using different morbilliviruses. The mAbs could broadly be categorized as; CDV specific (CD-3D8 and CD-2F8), cross-reactive to PPR virus (CD-AB3 and CD-4D6) and cross-reactive to both PPR virus and measles virus (CD-5D10 and CD-6E5). The characterized mAbs were used for antigenic profiling of CDV, PPR virus and measles virus. Based on the reactivity pattern; a close antigenic relationship was found among CDV and PPR virus as compared to measles virus. A pair of CDV specific mAbs namely CD-2F8 and CD-3D8 were identified which did not cross-react with measles and PPR viruses and thus could be used for diagnostic applications.
Topics: Animals; Antibodies, Monoclonal; Distemper Virus, Canine; Dogs; Immunoglobulin G; Measles virus; Mice; Nucleocapsid Proteins; Peste-des-petits-ruminants virus
PubMed: 36096853
DOI: 10.1016/j.biologicals.2022.08.005 -
Journal of Clinical Virology : the... Aug 2014Ireland is classified as an area of high measles incidence. A World Health Organisation-European Region strategic plan exists for measles elimination by 2015.
BACKGROUND
Ireland is classified as an area of high measles incidence. A World Health Organisation-European Region strategic plan exists for measles elimination by 2015.
OBJECTIVES
To retrospectively investigate measles outbreaks using all patient samples (sera and oral fluid) received for measles laboratory diagnosis and characterise the genetic diversity of circulating measles genotypes in Ireland.
STUDY DESIGN
704 cases of acute measles infection as determined by the presence of measles specific IgM in sera and oral fluids were confirmed at the National Virus Reference Laboratory. Measles positive samples (n=116) were examined by genotyping, sequence analysis and phylogenetic characterisation.
RESULTS
Three measles outbreaks occurred over the study period: 2004, 2009/2010 and 2011. Measles IgM positivity ranged from 22-29% in outbreak years to 5-10% in the intervening years. Age profile analysis revealed that whereas individuals >10 years accounted for only 8% of cases in the 2004 outbreak, this increased to 33% and 29% in the 2009/2010 and 2011 outbreaks, respectively. The <1 year cohort accounted for 18-20% of cases in all outbreaks. Phylogenetic analysis demonstrated both indigenous transmission and also importation events. Clade D viruses were exclusively found circulating in Ireland, with autochthonous transmission of diverse genotype D4 strains associated with large outbreaks across Europe. More recently, genotype D8 was identified and these were associated with importation events.
CONCLUSIONS
This study provides a comprehensive genetic analysis of circulating measles genotypes in Ireland and discriminated between indigenous and imported viral strains. Notably, an increase in laboratory-confirmed measles cases in the greater than 10 years of age group was seen over the study period. This information is valuable to inform vaccination strategies with a focus on those populations who remain susceptible to measles infection.
Topics: Adolescent; Aging; Antibodies, Viral; Base Sequence; Child; Child, Preschool; Disease Outbreaks; Female; Genetic Variation; Humans; Immunoglobulin M; Infant; Ireland; Male; Measles; Measles virus; Measles-Mumps-Rubella Vaccine; Phylogeny; RNA, Viral; Retrospective Studies; Sequence Analysis, RNA; Seroepidemiologic Studies; Vaccination; Young Adult
PubMed: 24929750
DOI: 10.1016/j.jcv.2014.05.010 -
Journal of Virology May 2017Measles virus (MeV) is a member of the family that causes a highly contagious respiratory disease but has emerged as a promising oncolytic platform. Previous studies of...
Measles virus (MeV) is a member of the family that causes a highly contagious respiratory disease but has emerged as a promising oncolytic platform. Previous studies of MeV entry focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express the MeV receptors SLAM (signaling lymphocyte-activating molecule) and PVRL4 (poliovirus receptor-like 4) (nectin-4). Recombinant MeVs expressing either firefly luciferase or green fluorescent protein together with a variety of inhibitors were used. The results showed that MeV uptake was dynamin independent in the Vero.hPVRL4, Vero.hSLAM, and PVRL4-positive MCF7 breast cancer cell lines. However, MeV infection was blocked by 5-(-ethyl--propyl)amiloride (EIPA), the hallmark inhibitor of macropinocytosis, as well as inhibitors of actin polymerization. By using phalloidin staining, MeV entry was shown to induce actin rearrangements and the formation of membrane ruffles accompanied by transient elevated fluid uptake. Small interfering RNA (siRNA) knockdown of p21-activated kinase 1 (PAK1) demonstrated that MeV enters both Vero.hPVRL4 and Vero.hSLAM cells in a PAK1-independent manner using a macropinocytosis-like pathway. In contrast, MeV entry into MCF7 human breast cancer cells relied upon Rac1 and its effector PAK1 through a PVRL4-mediated macropinocytosis pathway. MeV entry into DLD-1 colon and HTB-20 breast cancer cells also appeared to use the same pathway. Overall, these findings provide new insight into the life cycle of MeV, which could lead to therapies that block virus entry or methods that improve the uptake of MeV by cancer cells during oncolytic therapy. In the past decades, measles virus (MeV) has emerged as a promising oncolytic platform. Previous studies concerning MeV entry focused mainly on the identification of putative receptors for MeV. Nectin-4 (PVRL4) was recently identified as the epithelial cell receptor for MeV. However, the specific endocytic and trafficking pathways utilized during MeV infections are poorly documented. In this study, we demonstrated that MeV enters host cells via a dynamin-independent and actin-dependent endocytic pathway. Moreover, we show that MeV gains entry into MCF7, DLD-1, and HTB-20 cancer cells through a PVRL4-mediated macropinocytosis pathway and identified the typical cellular GTPase and kinase involved. Our findings provide new insight into the life cycle of MeV, which may lead to the development of therapies that block the entry of the virus into the host cell or alternatively promote the uptake of oncolytic MeV into cancer cells.
Topics: Actins; Amiloride; Animals; Breast Neoplasms; Cell Adhesion Molecules; Cell Line; Chlorocebus aethiops; Colonic Neoplasms; Epithelial Cells; Female; Humans; MCF-7 Cells; Measles virus; Oncolytic Viruses; Pinocytosis; RNA, Small Interfering; Vero Cells; Virus Internalization; p21-Activated Kinases
PubMed: 28250131
DOI: 10.1128/JVI.02191-16 -
Science Advances Apr 2020Many viruses are known to form cellular compartments, also called viral factories. Paramyxoviruses, including measles virus, colocalize their proteomic and genomic...
Many viruses are known to form cellular compartments, also called viral factories. Paramyxoviruses, including measles virus, colocalize their proteomic and genomic material in puncta in infected cells. We demonstrate that purified nucleoproteins (N) and phosphoproteins (P) of measles virus form liquid-like membraneless organelles upon mixing in vitro. We identify weak interactions involving intrinsically disordered domains of N and P that are implicated in this process, one of which is essential for phase separation. Fluorescence allows us to follow the modulation of the dynamics of N and P upon droplet formation, while NMR is used to investigate the thermodynamics of this process. RNA colocalizes to droplets, where it triggers assembly of N protomers into nucleocapsid-like particles that encapsidate the RNA. The rate of encapsidation within droplets is enhanced compared to the dilute phase, revealing one of the roles of liquid-liquid phase separation in measles virus replication.
Topics: Magnetic Resonance Spectroscopy; Measles; Measles virus; Nucleocapsid; Nucleoproteins; Phosphoproteins; Protein Binding; Protein Interaction Domains and Motifs; RNA, Viral; Recombinant Proteins; Thermodynamics; Viral Proteins; Virus Assembly; Virus Replication
PubMed: 32270045
DOI: 10.1126/sciadv.aaz7095 -
Travel Medicine and Infectious Disease 2019
Topics: Disease Outbreaks; Humans; Madagascar; Male; Measles; Measles virus; Middle Aged; Travel; Vaccination Coverage
PubMed: 30954543
DOI: 10.1016/j.tmaid.2019.04.003 -
Infection, Genetics and Evolution :... Mar 2017Molecular surveillance and advanced phylogenetic methods are important tools to track the pathways of Measles virus (MV) genotypes, provide evidence for the interruption...
Molecular surveillance and advanced phylogenetic methods are important tools to track the pathways of Measles virus (MV) genotypes, provide evidence for the interruption of endemic transmission and verify the elimination of the disease. The aims of this study were to describe the genetic profile of MV genotype D8 (D8-MV) strains circulating in Northern Italy (Lombardy Region) during the 2013-2014 period and to analyze the transmission chains and estimate the introduction time points using a phylogenetic approach. Forty-four strains of D8-MV identified from 12 outbreaks and 28 cases reported as sporadic were analyzed. Molecular analysis was performed by sequencing the highly variable 450nt region of the N gene of MV genome (N-450), as recommended by the WHO. Phylogenetic analyses and tree time-scaled reconstruction were performed with BEAST software. We could trace back the transmission pathways that resulted in three chains of transmission, two introductions with limited spread (two familiar outbreaks), and two single introductions (true sporadic cases). The D8-Taunton transmission chain, which was involved in 7 outbreaks and 13 sporadic cases, was endemic during the studied period. Furthermore, two novel local variants emerged independently in March 2014 and caused two transmission chains linked to at least 3 outbreaks. Overall, viral diversity was high and strains belonging to 5 different variants were identified. The results of this study clearly demonstrate that multiple lineages of D8-MV co-circulated in Northern Italy. Measles can be considered a re-emerging disease in Italy and additional efforts are necessary to achieve measles elimination goal.
Topics: Communicable Diseases, Emerging; Disease Outbreaks; Evolution, Molecular; Genetic Variation; Genotype; Humans; Italy; Measles; Measles virus; Molecular Epidemiology; Phylogeny; RNA, Viral; Sequence Analysis, DNA; Viral Proteins
PubMed: 27989661
DOI: 10.1016/j.meegid.2016.12.013 -
Uirusu 2017A large-scale national measles epidemic occurred among mainly in teenagers and young adults in 2007. MHLW announced ''Special infectious disease prevention guidelines... (Review)
Review
A large-scale national measles epidemic occurred among mainly in teenagers and young adults in 2007. MHLW announced ''Special infectious disease prevention guidelines for measles'' (issued on 28 December 2007; Revised issued on 30 March 2013), and Japan decided the elimination target year was fiscal year (FY) 2015. In 2008, it continued to be a large-scale nation epidemic exceeding 10,000 cases, and a large number of 0 to 1 year old infants, teenagers and young adults were suffering. Many cases were unvaccinated, single dose vaccination or unknown vaccination history. The number of measles cases has declined dramatically since 2009, and the measles virus of genotype D5, which was the indigenous strain in Japan, was not detected at the end of May 2010. Regional epidemics were approved in 2011 and 2014, starting from imported cases from overseas, but it ended early. Since 2006, a two-dose routine vaccination regimen of measles rubella combined (MR) vaccine has started, moreover in the 5 years from fiscal 2008, the second dose of MR vaccine for junior high school students and high school students was periodically inoculated and immunization strengthened for teens was done. As a result, antibody positive rate of 95% or more is maintained in all age groups over 2 years old. In March 2015, Japan's measles elimination was certified by the WHO Western Pacific Regional Office. In 2017, outbreaks occurred in adults originating from imported cases from Asia or Europe, but early termination declarations have been made by aggressive measures by local public health centers/institutes. The annual number of reported cases after measles elimination certification is less than 200 cases.
Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Genotype; Humans; Japan; Measles; Measles Vaccine; Measles virus; Time Factors; Young Adult
PubMed: 29593147
DOI: 10.2222/jsv.67.17 -
Scientific Reports Sep 2019Based on measles surveillance in Shanghai, People's Republic of China, from 2006 to 2015, we found that measles virus isolates from 40 throat swab samples exhibited... (Clinical Trial)
Clinical Trial
Based on measles surveillance in Shanghai, People's Republic of China, from 2006 to 2015, we found that measles virus isolates from 40 throat swab samples exhibited atypical cytopathic effects in Vero/hSLAM cells, which was found to be a result of coinfection with measles virus (MeV) and human herpes simplex virus type 1 (HSV-1). Serological and molecular approaches were used to confirm and characterize the coinfections in these patients. Among the 40 measles cases, measles-specific IgM was detected in 37 cases, while measles-specific IgG was detected in 27 cases. HSV-1-specific IgM and IgG were detected in 7 and 34 cases, respectively, suggesting that most of the MeV infections were primary, but that HSV-1 infection was due to the reactivation of latent virus in most cases. The titers of HSV-1 IgG in patients with either measles or measles-HSV-1 coinfection were significantly higher than those in the healthy group (P = 0.0026 and P < 0.0001, respectively); however, there was no significant difference in the titers of HSV-1 IgG in the MeV and MeV-HSV-1 coinfection patients (P = 0.105). Nucleic acids from MeV and HSV-1 were detected in 40 and 39 throat swabs, respectively. Twenty five MeV RNA sequences were genotyped, and all represented genotype H1, which is the endemic genotype in China. Sequences from the glycoprotein G gene of HSV-1 were used to classify the isolates into two distinct phylogenetic groups: 34 belonged to group A and 3 belonged to group B.
Topics: Adolescent; Adult; Antibodies, Viral; Child; Child, Preschool; China; Coinfection; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulin M; Infant; Male; Measles; Measles virus; Middle Aged; Phylogeny; RNA, Viral
PubMed: 31484944
DOI: 10.1038/s41598-019-48994-5