scholarly journals Molecular and seroepidemiologic studies of Enterovirus 71 infection in the State of Pará, Brazil

Author(s):  
Ceyla M.O. Castro ◽  
Ana Cecília R. Cruz ◽  
Edson E. da Silva ◽  
Maria de Lourdes C. Gomes

In many countries, the Enterovirus 71 (EV-71) Picornaviridae family is associated to hand, foot and mouth disease in addition to acute neurological diseases while in Brazil these viruses are more closely associated to the latter group. The aim of this research was to use the first EV-71 isolate of the Northern region of Brazil in molecular and seroepidemiologic studies. Two (2.2%) out of 88 stool samples (44 cases of AFP), collected from January 1998 to December 2000 were positive for EV-71 isolation (73442/PA/99). Nucleotide sequence of the gen that codifies the VP1 protein showed that isolate 73442/PA/99 was similar to the EV-71 strains belonging to genotype B - more closely identified with EV-71 from North America. Neutralization test with 389 sera samples collected from January 1998 to November 2001, from individuals ranging from 0 to 15 years of age living in the city of Belém, State of Pará showed the following results in relation to isolate 73442/PA/99 and prototype BrCr: a total of 207 individuals (53.2%) had neutralization antibodies to both viruses, 167 (42.9%) had no antibodies and 15 showed the presence of neutralizing antibodies to one of the two viruses. Only 20.2% of the children aged 0 to 3 had neutralizing antibodies to EV-71, indicating that these children were more susceptible to the infection. Both the seroprevalence study and VP1 sequencing were important to demonstrate the spread and the molecular pattern of the EV-71 circulating in the Northern Region of Brazil.

2019 ◽  
Vol 20 (6) ◽  
pp. 1256 ◽  
Author(s):  
Mohd Anasir ◽  
Chit Poh

Hand, foot, and mouth disease (HFMD) commonly produces herpangina, but fatal neurological complications have been observed in children. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) are the predominant viruses causing HFMD worldwide. With rising concern about HFMD outbreaks, there is a need for an effective vaccine against EV-A71 and CV-A16. Although an inactivated vaccine has been developed against EV-A71 in China, the inability of the inactivated vaccine to confer protection against CV-A16 infection and other HFMD etiological agents, such as CV-A6 and CV-A10, necessitates the exploration of other vaccine platforms. Thus, the antigenic peptide-based vaccines are promising platforms to develop safe and efficacious multivalent vaccines, while the monoclonal antibodies are viable therapeutic and prophylactic agents against HFMD etiological agents. This article reviews the available information related to the antigenic peptides of the etiological agents of HFMD and their neutralizing antibodies that can provide a basis for the design of future therapies against HFMD etiological agents.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
C. Q. Hoang ◽  
H. D. Nguyen ◽  
N. X. Ho ◽  
T. H. T. Vu ◽  
T. T. M. Pham ◽  
...  

Background. Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. Methods. We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. Results. The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. Conclusions. Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.


2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Xiaoli Wang ◽  
Zhiqiang Ku ◽  
Xiang Zhang ◽  
Xiaohua Ye ◽  
Jinhuan Chen ◽  
...  

ABSTRACTEnterovirus 71 (EV71) is the major causative agent of severe hand, foot, and mouth disease, which affects millions of young children in the Asia-Pacific region annually. In this study, we engineered a novel EV71 virus-like particle (VLP) that lacks VP4 (therefore designated VLPΔVP4) and investigated its structure, antigenicity, and vaccine potential. The cryo-electron microscopy (cryo-EM) structure of VLPΔVP4was reconstructed to 3.71-Å resolution. Results from structural and biochemical analyses revealed that VLPΔVP4resembles the end product of the viral uncoating process, the 80S empty capsid. VLPΔVP4is able to elicit high-titer neutralizing antibodies and to fully protect mice against lethal viral challenge. Mechanistic studies showed that, at the cellular level, the anti-VLPΔVP4sera exert neutralization effects at both pre- and postattachment stages by inhibiting both virus attachment and internalization, and at the molecular level, the antisera can block multiple interactions between EV71 and its key receptors. Our study gives a better understanding of EV71 capsid assembly and provides important information for the design and development of new-generation vaccines for EV71, and perhaps for other enteroviruses, as well.IMPORTANCEEnterovirus 71 (EV71) infection may lead to severe hand, foot, and mouth disease, with significant morbidity and mortality. Knowledge regarding EV71 particle assembly remains limited. Here, we report the generation and characterization of a novel EV71 virus-like particle that lacks the VP4 capsid subunit protein. This particle, termed VLPΔVP4, structurally mimics the 80S empty capsid, which is the end stage of EV71 uncoating. We further show that VLPΔVP4exhibits desirable immunogenicity and protective efficacy in proof-of-concept studies. In addition, the inhibitory mechanisms of the VLPΔVP4-induced antibodies are unraveled at both the cellular and molecular levels. Our work provides the first evidence of picornaviral particle assembly in the complete absence of VP4 and identifies VLPΔVP4as an improved EV71 vaccine candidate with desirable traits. These findings not only enhance our understanding of particle assembly and uncoating of picornaviruses, but also provide important information for structure-guided vaccine design for EV71 and other enteroviruses.


Author(s):  
Mahsa Javadi ◽  
Ahmad Nejati ◽  
Maryam Yousefi ◽  
Mahmood Mahmoodi ◽  
Zabihollah Shoja ◽  
...  

Background and Objectives: Human Enterovirus 71 (EV-A71) is the causative agent for many dermal to neurological diseases especially polio-like paralysis outbreaks around the world. This study, the first of this kind in Iran, aimed to find neu- tralizing antibodies against EV-A71 in serum of healthy individuals in different age groups based on neutralization test (NT). Materials and Methods: In this cross-sectional study, 547 serum samples were collected from healthy individuals who were referring for routine checkup tests (aged from under 6 months to over 31 years old) to Imam-Khomeini Hospital in Tehran during January-December 2015. Serum samples were examined by NT in cell culture to detect neutralizing antibodies against EV-A71. In the next step, some of the positive samples were subjected to complete titration to determine the exact titer of anti-EV-A71 antibodies. Results: Of 547 samples, 310 (56.7%) were positive for EV-A71 neutralizing antibody. The presence of the antibody in- creased with age (p<0.001), and there was a significant statistical relationship between sex and the presence of antibody (p=0.009). Conclusion: Our results demonstrated an apparent but limited circulation of EV-A71 in our society. After the worldwide eradication of poliovirus, EV-A71 which can cause polio-likes syndrome, might be the new challenge for our health care system as regard more in depth research is however needed.


2015 ◽  
Vol 89 (23) ◽  
pp. 12084-12095 ◽  
Author(s):  
Zhiqiang Ku ◽  
Xiaohua Ye ◽  
Jinping Shi ◽  
Xiaoli Wang ◽  
Qingwei Liu ◽  
...  

ABSTRACTAntibodies play a critical role in immunity against enterovirus 71 (EV71). However, how EV71-specific antibodies neutralize infections remains poorly understood. Here we report the working mechanism for a group of three monoclonal antibodies (MAbs) that potently neutralize EV71. We found that these three MAbs (termed D5, H7, and C4, respectively) recognize the same conserved neutralizing epitope within the VP1 GH loop of EV71. Single MAbs in this group, exemplified by D5, could inhibit EV71 infection in cell cultures at both the pre- and postattachment stages in a cell type-independent manner. Specifically, MAb treatment resulted in the blockade of multiple steps of EV71 entry, including virus attachment, internalization, and subsequent uncoating and RNA release. Furthermore, we show that the D5 and C4 antibodies can interfere with EV71 binding to its key receptors, including heparan sulfate, SCARB2, and PSGL-1, thus providing a possible explanation for the observed multi-inhibitory function of the MAbs. Collectively, our study unravels the mechanism of neutralization by a unique group of anti-EV71 MAbs targeting the conserved VP1 GH loop. The findings should enhance our understanding of MAb-mediated immunity against enterovirus infections and accelerate the development of MAb-based anti-EV71 therapeutic drugs.IMPORTANCEEnterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which has caused significant morbidities and mortalities in young children. Neither a vaccine nor an antiviral drug is available. Neutralizing antibodies are major protective components in EV71 immunity. Here, we unraveled an unusual mechanism of EV71 neutralization by a group of three neutralizing monoclonal antibodies (MAbs). All of these MAbs bound the same conserved epitope located at the VP1 GH loop of EV71. Interestingly, mechanistic studies showed that single antibodies in this MAb group could block EV71 attachment and internalization during the viral entry process and interfere with EV71 binding to heparan sulfate, SCARB2, and PSGL-1 molecules, which are key receptors involved in different steps of EV71 entry. Our findings greatly enhance the understanding of the interplays among EV71, neutralizing antibodies, and host receptors, which in turn should facilitate the development of an MAb-based anti-EV71 therapy.


1999 ◽  
Vol 73 (12) ◽  
pp. 9969-9975 ◽  
Author(s):  
Betty A. Brown ◽  
M. Steven Oberste ◽  
James P. Alexander ◽  
Margery L. Kennett ◽  
Mark A. Pallansch

ABSTRACT Enterovirus 71 (EV71) (genus Enterovirus, familyPicornaviridae), a common cause of hand, foot, and mouth disease (HFMD), may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity and rate of evolution of EV71, we have determined and analyzed complete VP1 sequences (891 nucleotides) for 113 EV71 strains isolated in the United States and five other countries from 1970 to 1998. Nucleotide sequence comparisons demonstrated three distinct EV71 genotypes, designated A, B, and C. The genetic variation within genotypes (12% or fewer nucleotide differences) was less than the variation between genotypes (16.5 to 19.7%). Strains of all three genotypes were at least 94% identical to one another in deduced amino acid sequence. The EV71 prototype strain, BrCr-CA-70, isolated in California in 1970, is the sole member of genotype A. Strains isolated in the United States and Australia during the period from 1972 to 1988, a 1994 Colombian isolate, and isolates from a large HFMD outbreak in Malaysia in 1997 are all members of genotype B. Although strains of genotype B continue to circulate in other parts of the world, none have been isolated in the United States since 1988. Genotype C contains strains isolated in 1985 or later in the United States, Canada, Australia, and the Republic of China. The annual rate of evolution within both the B and C genotypes was estimated to be approximately 1.35 × 10−2 substitutions per nucleotide and is similar to the rate observed for poliovirus. The results indicate that EV71 is a genetically diverse, rapidly evolving virus. Its worldwide circulation and potential to cause severe disease underscore the need for additional surveillance and improved methods to identify EV71 in human disease.


Clean Energy ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 57-78
Author(s):  
Sohaib Nasr Mohamed Abdalla ◽  
Hakan Özcan

Abstract Developing nations have a critical need to increase electricity supply. Sudan has much unrealized potential for generating solar energy, particularly in the northern region. This research study focuses on designing a 1-GW solar power station in northern Sudan using the PVsyst7.0 software program. To determine the appropriate location for the solar-energy station, 14 criteria were evaluated. This process is generic and suitable for use in any other country. The method for conducting cash-flow estimates and return on investment is illustrated in the economic evaluation. The city of Dongola, the capital of the northern state, was selected because of its high annual irradiance on a horizontal surface at ~2333.2 kWh/m2. The simulation results show that the annual optimum tilt angle of inclination for photovoltaic (PV) modules is 30°, the energy production is 1 979 259 MWh/yr and the average annual performance rate is 0.810. In addition, the electric power consumption per capita in Sudan is 269 kWh/yr, so the proposed solar power plant with 1 979 259 MWh/yr can provide energy to 7.4 million people per year annually and reduce carbon emissions by ~18 million tons of carbon dioxide per year. Economic calculations show that the levelized cost of electricity (LCOE) is $0.06/kWh, the discounted payback period is ~11 years and the net present value is $635 291 000. As a result, the proposed grid-connected PV solar plant is considered economically, technically and environmentally feasible in Sudan.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 593
Author(s):  
Václav Šimánek ◽  
Ladislav Pecen ◽  
Zuzana Krátká ◽  
Tomáš Fürst ◽  
Hana Řezáčková ◽  
...  

There is an ongoing debate as to whether SARS-CoV-2 antibodies can be found in patients who have recovered from COVID-19 disease. Currently, there is no consensus on whether the antibodies, if present, are protective. Our regular measurements of SARS-CoV-2 antibodies, starting in July 2020, have provided us with the opportunity of becoming acquainted with the five different immunoassays. A total of 149 patients were enrolled in our study. We measured the samples using each immunoassay, then performing a virus neutralization test and comparing the results of SARS-CoV-2 antibodies with this test. We observed that the production of neutralizing antibodies is age-dependent. Elderly patients have a higher proportion of high neutralizing titers than young patients. Based on our results, and in combination with the literature findings, we can conclude that the serological SARS-CoV-2 antibody measurement is a helpful tool in the fight against COVID-19. The assays can provide information about the patient’s previous contact with the virus. Anti-spike protein assays correlate well with the virus neutralization test and can be used in the screening of potential convalescent plasma donors.


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