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Viruses Mar 2020Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include... (Review)
Review
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies.
Topics: Animals; Antiviral Agents; Binding Sites; Drug Discovery; Humans; Models, Molecular; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Protein Binding; Structure-Activity Relationship; Virus Internalization
PubMed: 32245118
DOI: 10.3390/v12030342 -
Science (New York, N.Y.) Jun 2020Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the...
Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the sixth century BCE, possibly coinciding with the rise of large cities.
Topics: Cities; Communicable Diseases, Emerging; Evolution, Molecular; Genetic Variation; History, Ancient; Humans; Measles; Measles virus; Rinderpest virus
PubMed: 32554594
DOI: 10.1126/science.aba9411 -
One Health (Amsterdam, Netherlands) Dec 2023Measles infections can cause significant morbidity and mortality in human and monkey populations. The endemicity of measles in human populations and viral circulation...
Measles infections can cause significant morbidity and mortality in human and monkey populations. The endemicity of measles in human populations and viral circulation within populations of free-living monkeys may have important repercussions for potential zoonotic transmission events and for the long-term health of monkey populations. Yet, there has not yet been a rigorous investigation of the dynamics of measles transmission where human and monkey populations coexist. In this study, to determine the difference in seroprevalence of the measles virus across different contexts of human-monkey contact, we analyzed serum samples collected from 56 apparently healthy monkeys who occupied diverse contexts, with different degrees of human-monkey contact, in Bangladesh. This is the first report of measles virus seroprevalence in monkeys in Bangladesh. We found a clear association between measles virus seropositivity in monkeys and the context in which they interact with humans. Seroprevalence was the lowest in wild areas (0.0%) and increased in shrines (4.8%), urban areas (5.9%), and was highest among monkeys who are used as performance animals (50.0%). This work suggests that a One Health approach informed by local interspecies transmission dynamics is necessary to develop strategies that both improve measles vaccination coverage, achieve long-term surveillance in monkey populations, and prevent measles spillback to monkeys. This approach aims to inform conservation efforts and protect the long-term health of human and monkey populations.
PubMed: 37332882
DOI: 10.1016/j.onehlt.2023.100571 -
Current Opinion in Virology Apr 2020The innate immune system is the first line of defense against infections with pathogens. It provides direct antiviral mechanisms to suppress the viral life cycle at... (Review)
Review
The innate immune system is the first line of defense against infections with pathogens. It provides direct antiviral mechanisms to suppress the viral life cycle at multiple steps. Innate immune cells are specialized to recognize pathogen infections and activate and modulate adaptive immune responses through antigen presentation, co-stimulation and release of cytokines and chemokines. Measles virus, which causes long-lasting immunosuppression and immune-amnesia, primarily infects and replicates in innate and adaptive immune cells, such as dendritic cells, macrophages, T cells and B cells. To achieve efficient replication, measles virus has evolved multiple mechanisms to manipulate innate immune responses by both stimulation and blocking of specific signals necessary for antiviral immunity. This review will highlight our current knowledge in this and address open questions.
Topics: Animals; Cytokines; Host-Pathogen Interactions; Humans; Immunity, Innate; Measles; Measles virus; Virus Replication
PubMed: 32330821
DOI: 10.1016/j.coviro.2020.03.001 -
Frontiers in Medicine 2022Although the highly effective measles vaccine has dramatically reduced the incidence of measles, measles, and outbreaks continue to occur in individuals who received the...
Although the highly effective measles vaccine has dramatically reduced the incidence of measles, measles, and outbreaks continue to occur in individuals who received the measles vaccine because of immunization failure. In this study, patients who have definite records of immunization were enrolled based on measles surveillance in Shanghai, China, from 2009 to 2017, and genomic characteristics regarding viruses retrieved from these cases provided insights into immunization failure. A total of 147 complete genomes of measles virus (MV) were obtained from the laboratory-confirmed cases through Illumina MiSeq. Epidemiological, and genetic characteristics of the MV were focused on information about age, gender, immunization record, variation, and evolution of the whole genome. Furthermore, systematic genomics using phylogeny and selection pressure approaches were analyzed. Our analysis based on the whole genome of 147 isolates revealed 4 clusters: 2 for the genotype H1 (clusters named H1-A, including 73 isolates; H1-B, including 72 isolates) and the other 2 for D8 and B3, respectively. Estimated nucleotide substitution rates of genotype H1 MV derived using genome and individual genes are lower than other genotypes. Our study contributes to global measles epidemiology and proves that whole-genome sequencing was a useful tool for more refined genomic characterization. The conclusion indicates that vaccination may have an effect on virus evolution. However, no major impact was found on the antigenicity in Shanghai isolates.
PubMed: 35847814
DOI: 10.3389/fmed.2022.841650 -
Viruses May 2022Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young... (Review)
Review
Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.
Topics: Antiviral Agents; COVID-19; Child; Humans; Measles; Measles Vaccine; Measles virus; Pandemics; Vaccination
PubMed: 35746658
DOI: 10.3390/v14061186 -
The Canadian Journal of Infectious... 2020Measles remains a public health concern in many regions, and the imported measles cases continue to challenge the measles elimination program for most of the countries...
Measles remains a public health concern in many regions, and the imported measles cases continue to challenge the measles elimination program for most of the countries where measles was verified to be eliminated or approaching elimination. The imported measles cases have been reported since October, 2017, in Jiangsu province, China. In this study, we reported the first imported B3 genotype measles virus from Egypt and the second imported D8 genotype measles virus from Philippines through international traveling. No secondary measles cases were found after these imported cases. Our findings highlighted the importance of measles vaccination targeting international travelers in China.
PubMed: 32089759
DOI: 10.1155/2020/7318582 -
The Journal of Infectious Diseases Jul 2019Chikungunya virus (CHIKV) infection can result in chikungunya fever (CHIKF), a self-limited acute febrile illness that can progress to chronic arthralgic sequelae in a...
BACKGROUND
Chikungunya virus (CHIKV) infection can result in chikungunya fever (CHIKF), a self-limited acute febrile illness that can progress to chronic arthralgic sequelae in a large percentage of patients. A new measles virus-vectored vaccine was developed to prevent CHIKF, and we tested it for immunogenicity and efficacy in a nonhuman primate model.
METHODS
Nine cynomolgus macaques were immunized and boosted with the measles virus-vectored chikungunya vaccine or sham-vaccinated. Sera were taken at multiple times during the vaccination phase to assess antibody responses against CHIKV. Macaques were challenged with a dose of CHIKV previously shown to cause fever and viremia, and core body temperature, viremia, and blood cell and chemistry panels were monitored.
RESULTS
The vaccine was well tolerated in all macaques, and all seroconverted (high neutralizing antibody [PRNT80 titers, 40-640] and enzyme-linked immunosorbent assay titers) after the boost. Furthermore, the vaccinated primates were protected against viremia, fever, elevated white blood cell counts, and CHIKF-associated cytokine changes after challenge with the virulent La Reunión CHIKV strain.
CONCLUSIONS
These results further document the immunogenicity and efficacy of a measles-vectored chikungunya vaccine that shows promise in Phase I-II clinical trials. These findings are critical to human health because no vaccine to combat CHIKF is yet licensed.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Body Temperature; Chikungunya Fever; Chikungunya virus; Cytokines; Disease Models, Animal; Female; Genetic Vectors; Humans; Immunization, Secondary; Immunogenicity, Vaccine; Macaca fascicularis; Male; Measles; Measles Vaccine; Measles virus; Vaccination; Viral Vaccines; Viremia
PubMed: 31053842
DOI: 10.1093/infdis/jiz202 -
Journal of Medical Virology Oct 2023In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a...
In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV-6) and 7 (HHV-7), parvovirus B19 (B19V), enterovirus (EV), Epstein-Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS-CoV-2. Differential diagnosis was carried out on 289 discarded cases by multiplex real-time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV-7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV-6, EV, HAdV, and HCMV-positive cases were found in children aged 0-4 years and HHV-7 was most frequent in the 15-39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus-positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities.
Topics: Child; Humans; Adolescent; Young Adult; Adult; Diagnosis, Differential; Epstein-Barr Virus Infections; Antibodies, Viral; Immunoglobulin M; Herpesvirus 4, Human; Measles; Rubella; Measles virus; Enterovirus; Exanthema; Fever; Enterovirus Infections; Herpesvirus 6, Human; Adenoviruses, Human
PubMed: 37796084
DOI: 10.1002/jmv.29141 -
Vaccines Nov 2019Despite efforts to improve surveillance and vaccination coverage, measles virus (MeV) continues to cause outbreaks also in high-income countries. As the reference...
Despite efforts to improve surveillance and vaccination coverage, measles virus (MeV) continues to cause outbreaks also in high-income countries. As the reference laboratory of the Veneto Region, Italy, we analyzed changes in population immunity, described measles outbreaks, investigated MeV genetic diversity, and evaluated cross-protection of measles vaccination against MeV epidemic strains. Like most European areas, the Veneto Region has suboptimal measles vaccination coverage and is facing a growing public mistrust of vaccination. A progressive decline of measles vaccine uptake was observed during the last decade in the Veneto Region, leading to immunity gaps in children and young adults. Measles outbreaks were caused by the same MeV genotype B3, D4, and D8 strains that were circulating in other European countries. Eleven cases of measles were observed in immunized subjects. These cases were not associated with particular MeV genotypes nor with mutations in epitopes recognized by neutralizing antibodies. Accordingly, sera from fully vaccinated subjects cross-neutralized epidemic MeV strains, including the genotypes B3, D4, and D8, with the same high efficiency demonstrated against the vaccine strain. In fully vaccinated subjects, high MeV IgG antibody titers persisted up to 30 years following vaccination. These results support the use of the current measles-containing vaccines and strategies to strengthen vaccination.
PubMed: 31795157
DOI: 10.3390/vaccines7040199