CRISPR/Cas9-Mediated Gene Drive to Prevent the Replication of Dengue Virus in the Mosquito Vectors to Reduce the Impact of Dengue Epidemic in Bangladesh

2021 ◽  
pp. 63-68
Author(s):  
Masuma Afrin Taniya ◽  
Jessica Das Senjuti ◽  
Rashed Noor
Keyword(s):  
Dengue Virus ◽  
Dengue Infection ◽  
Drive System ◽  
Scfv Antibody ◽  
Gene Drive ◽  
Single Chain ◽  
Denv Serotypes ◽  
Novel Technology ◽  
The Government ◽  
The Impact

Dengue is a flavivirus transmitted by Aedes aegypti, leading to mosquito-borne illness causing significant morbidity and mortality each year. A majority of dengue cases around the world are caused by four serotypes-dengue virus (DENV) 1-4. The recent outbreak has broken all the previous record of infections with 101, 354 dengue cases, which has increased the urgency of finding an effective way to reduce the level of infection. CRISPR-Cas9 mediated gene drive is a novel technology that can be used to reduce the transmission by Aedes mosquitoes. Ae. aegypti can be engineered to express anti-DENV, 1C19-based, single-chain variable fragment (scFv) antibody, to provide protection against all four DENV serotypes by neutralizing them. Anti-DENV scFv-antibody transgene can be incorporated into a clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR associated (Cas); i.e., the CRISPR/Cas9-based gene drive system gene for effective suppression of dengue infection. CRISPR/Cas9-based gene drive system allows it to pass down this phenotype across the wild population in the urban area. However, the incautious release of gene drive in the environment can swipe away the entire population. This technology can greatly impact on the environment, creating an imbalance in the ecosystem if not applied carefully. Rigorous studies and mass level cooperation are needed among the scientists, local authorities and the government to make the informed decisions on the outcome of this technology.

scholarly journals Modeling Dengue Immune Responses Mediatedby Antibodies: A Qualitative Study

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 941
Author(s):  
Afrina Andriani Sebayang ◽  
Hilda Fahlena ◽  
Vizda Anam ◽  
Damián Knopoff ◽  
Nico Stollenwerk ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Antibody Production ◽  
Natural Infection ◽  
Severe Disease ◽  
Dengue Infection ◽  
Immunological Response ◽  
Health Concern ◽  
Future Research ◽  
Model Framework ◽  
The Impact

Dengue fever is a viral mosquito-borne infection and a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called antibody-dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: (i) primary dengue infection, (ii) secondary dengue infection with the same (homologous) dengue virus and (iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights into the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

scholarly journals Computational antigenic epitope prediction of clinical Indonesian Dengue virus NS1 protein

2021 ◽  
Vol 948 (1) ◽  
pp. 012080
Author(s):  
S Pambudi ◽  
D Irawan ◽  
A Danny ◽  
T Widayanti ◽  
Tarwadi
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
B Cell ◽  
Dengue Infection ◽  
Epitope Prediction ◽  
Antigenic Epitope ◽  
Ns1 Protein ◽  
Mhc I ◽  
B Cell Epitopes ◽  
Denv Serotypes

Abstract The identification of human Non-Structural-1 (NS1) protein epitopes will help us better understand Dengue virus (DENV) immunopathogenesis. In this study, several online and offline bioinformatic prediction tools were exploited to predict and analyze T-cell and B-cell epitopes of DENV NS1 consensus sequences originated from Indonesian clinical isolates. We identified a potential peptide at NS1155--163 (VEDYGFGIF) which interact with MHC-I allele HLA-B*40:01 and showed high binding affinity (IC50) scores ranging between 63.8 nM to 183.9 nM for all Indonesian DENV serotypes. Furthermore, we have succeeded identified a region at the C-terminal of Indonesian DENV NS1 protein between 325--344 as part of discontinuous antigenic epitope which conserved for all serotypes. Our analyses showed this region could induce strong and persistent antibody against all DENV serotypes by interacting with MHC-I molecule and also recognized by B-cell receptor. The identification of DENV NS1 T-cell and B-cell epitopes may help in the development of a new vaccine, drug discovery, and diagnostic system to help eradicate dengue infection.

scholarly journals The role of different serotypes and dengue virus concentration in the prognosis of dengue shock syndrome in children

2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Tram Van Ta ◽  
Hai Thanh Tran ◽  
Quyen Nguyen Than Ha ◽  
Xuong Tuyet Nguyen ◽  
Vu Kien Tran ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Denv Infection ◽  
Virus Concentration ◽  
Denv Serotypes ◽  
Significant Difference ◽  
Almost All ◽  
The Relationship

Dengue haemorrhagic fever (DHF) is a burden of disease in tropical countries, caused by any one of four-dengue virus (DENV) serotypes (DENV-1 to DENV-4). Although there have been many studies on patients with DHF, many things remain unclear, including the role of DENV serotypes and DENV concentration. The objective of this study was to determine the role of different serotypes and DENV concentration in the prognosis of dengue shock syndrome. This was a prospective cohort study, conducted to show information relating to patients’ conditions, such as hematocrit, platelet, leukocytes, and DENV concentration and the differences between DENV serotypes. The study also expressed the relationship between two groups, DHF without shock and DHF with shock, in terms of immune status, different DENV serotypes, and DENV concentration. Two-hundred and thirty-four patients were serologically confirmed as having a DENV infection. On hospital admission day (fever within 72 hours), results showed that almost all patients had a secondary dengue infection (76.5 %). DENV-1 accounted for the highest number of cases (61.11%), and DENV-4 accounted for the lowest (0.43%). No statistically significant difference was found when comparing the two groups (DHF with shock and DHF without shock) or when comparing the groups of different DENV serotypes. The study concluded that different DENV serotypes or DENV concentration in the first day of hospitalization (fever within 72 hours) cannot be used for prognostic of DSS.

scholarly journals On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes

2009 ◽  
Vol 90 (4) ◽  
pp. 799-809 ◽  
Author(s):  
Ravikumar Rajamanonmani ◽  
Celine Nkenfou ◽  
Paula Clancy ◽  
Yin Hoe Yau ◽  
Susana Geifman Shochat ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Viral Entry ◽  
Cross Reactivity ◽  
Binding Activity ◽  
Single Chain ◽  
Viral Attachment ◽  
Denv Serotypes ◽  
Humoral Immune ◽  
Single Chain Fv ◽  
Domain Iii

The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F12 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F12 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F12 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.

scholarly journals Diagnostic Performance of Dengue Virus Envelope Domain III in Acute Dengue Infection

2019 ◽  
Vol 20 (14) ◽  
pp. 3464 ◽  
Author(s):  
Ngoc Minh Nguyen ◽  
Bao Tuan Duong ◽  
Mudsser Azam ◽  
Truong Thai Phuong ◽  
Hyun Park ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Acute Phase ◽  
Clinical Symptoms ◽  
Dengue Infection ◽  
Protein Domain ◽  
Comparable Efficacy ◽  
Virus Envelope ◽  
Denv Serotypes ◽  
Diagnostic Potential ◽  
Domain Iii

Dengue, one of the most prevalent illnesses caused by dengue viruses that are members of the genus Flavivirus, is a significant global health problem. However, similar clinical symptoms and high antigenic homologies with other Flaviviruses in the endemic area pose difficulties for differential diagnosis of dengue from other arbovirus infections. Here, we investigated four types of recombinant envelope protein domain III (DV-rED III) derived from four dengue virus (DENV) serotypes for diagnostic potential in detecting IgM in acute phase (mainly 2–3 days after onset of fever). Each independent DV-1, -3, and -4-rED III-ELISA showed less than 60% sensitivity, but the combined results of DV-1, -3, and -4-rED III-ELISA led to sensitivity of 81.82% (18/22) (95% CI, 59.72 to 94.81) and 100% specificity (46/46) (95% CI, 92.29 to 100.00) as each antigen compensated the other antigen-derived negative result. In conclusion, the independent combination of data derived from each recombinant antigen (DV1-, DV3-, and DV4-rED III) showed comparable efficacy for the detection of IgM in patients with acute-phase dengue infection.

scholarly journals REVIEW ARTICLE: DEVELOPEMENT AND USING DENGUE VACCINE FOR DENGUE INFECTION VIRUS

2019 ◽  
Vol 3 (2) ◽  
pp. 8
Author(s):  
Firdaus Kabiru Massey ◽  
Rika Yulia
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Target Population ◽  
World Health ◽  
Dengue Virus Infection ◽  
High Incidence ◽  
The Government ◽  
One Year ◽  
Health Organization

Abstract : Tropical and subtropical countries are regions with high incidence of dengue infection. Dengue virus infection is estimated to cause 300 million new infections in one year and approximately 1 million severe cases with 2 + 5% deaths. The case of dengue in Indonesia has continued to increase since 1968 until 1980 where all provinces in Indonesia have been affected by the dengue virus. Dengue virus is a virus carried by the Aedes aegypti mosquito in its salivary gland. The virus which is a family group of Flaviviruses has four homologous serotypes, namely DENV-1, DENV-2, DENV-3, and DENV-4, which can cause dengue infection in individuals. Currently there is a shift in the target population from children to adults. This is a problem that needs to be resolved by the government and the community itself. Solution to overcome this, the government needs early prevention efforts to reduce the severity of dengue infection by developing and researching dengue vaccines. Currently a vaccine has been found that can be used as prophylaxis for dengue virus, namely Dengvaxia. This vaccine has been recommended by the World Health Organization (WHO) as prophylaxis for dengue infection, but Dengvaxia is only used in areas that are very endemic to dengue fever. The Indonesian Food and Drug Supervisory Agency (BPOM RI) has also approved the use of Dengvaxia as an indication of prevention of dengue infection since August 31, 2016. This vaccine has been approved globally only given to individuals aged between 9-16 years.  Keyword : dengue virus, dengvaxia vaccine, Aedes aegypti, endemic

scholarly journals DISTRIBUSI SEROTIPE DENGUE DI SURABAYA TAHUN 2012

2016 ◽  
Vol 19 (1) ◽  
pp. 41 ◽  
Author(s):  
Aryati Aryati ◽  
Puspa Wardhani ◽  
Benediktus Yohan ◽  
Eduardus Bimo Aksono H ◽  
R. Tedjo Sasmono
Keyword(s):  
Dengue Virus ◽  
Dengue Infection ◽  
Laboratory Diagnosis ◽  
Multiple Infections ◽  
Annual Change ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Dengue Disease ◽  
Denv Serotypes ◽  
Ns1 Antigen

The characteristics of epidemic dengue often presented as periods of hyperendemicity or as the co-circulation of multiple dengue serotypes. Surabaya is an endemic city for Dengue virus (DENV) transmission. Previous study of DENV distribution in 2008-2009 revealed the predominance of DENV-2. DENV serotypes distribution is known to be dynamic and serotype predominance may change through time. This study aims to determine and follow the circulation of DENV serotype in Surabaya in 2012. We recruited 154 denguesuspected patients attending Dr. Soetomo Hospital during February until August 2012. Dengue cases were confirmed by IgG and IgM serology tests and NS1 antigen detection. Serologically-positive samples were further analyzed using two-steps reverse transcriptasepolymerase chain reaction (RT-PCR) and viruses were isolated by propagation in C6/36 mosquito cell line. Seventy one cases (46.1%) were detected as DENV positive infection. Serotyping revealed that 61 samples have monotypic infection with one of all four of DENV serotypes and 10 samples have mix-infections. Overall serotyping result observed the predominance of DENV-1 (60.56%). Our result revealed the circulation of all four serotypes of DENV and the presence of serotype exchange in Surabaya in 2012. Annual change of predominant serotype and the presence of multiple infections may play an important role in the transmission of dengue infection. This information is valuable to dengue surveillance in the region. Therefore, the laboratory diagnosis of DENV serotype should be routinely performed to follow the dynamic of dengue disease

scholarly journals Modeling Dengue Immune Responses Mediated by Antibodies: a Qualitative Study

2021 ◽  
Author(s):  
Afrina Andriani Sebayang ◽  
Hilda Fahlena ◽  
Vizda Anam ◽  
Damián Knopoff ◽  
Nico Stollenwerk ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Antibody Production ◽  
Natural Infection ◽  
Severe Disease ◽  
Dengue Infection ◽  
Immunological Response ◽  
Health Concern ◽  
Future Research ◽  
Model Framework ◽  
The Impact

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: i) primary dengue infection, ii) secondary dengue infection with the same (homologous) dengue virus and iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production, and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights on the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

scholarly journals Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

2021 ◽  
Vol 15 (7) ◽  
pp. e0009641
Author(s):  
Chelsea M. Crooks ◽  
Andrea M. Weiler ◽  
Sierra L. Rybarczyk ◽  
Mason I. Bliss ◽  
Anna S. Jaeger ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Maternal Plasma ◽  
Adverse Outcomes ◽  
Primate Model ◽  
Denv Serotypes ◽  
The Impact ◽  
Human Primate ◽  
Maternal Fetal Interface

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

Prinsip Kearifan Lokal dalam Pengembangan Strategi Kehumasan pada Pemerintah Daerah Kabupaten Bandung

2020 ◽  
Vol 4 (2) ◽  
pp. 229-248
Author(s):  
Betty Tresnawaty
Keyword(s):  
Public Relations ◽  
Local Knowledge ◽  
Case Study Approach ◽  
West Java ◽  
Study Approach ◽  
Positive Image ◽  
The Government ◽  
The Impact ◽  
Public Relations Strategy

Public Relations of the Bandung Regency Government realizes that its area has a lot of potential for various local wisdom and has a heterogeneous society. This study aims to explore and analyze the values of local knowledge in developing public relations strategies in the government of Bandung Regency, West Java province. This study uses a constructivist interpretive (subjective) paradigm through a case study approach. The results showed that the Bandung Regency Government runs its government based on local wisdom. Bandung Regency Public Relations utilizes local insight and the region's potential to develop a public relations strategy to build and maintain a positive image of Bandung Regency. The impact of this research is expected to become a source of new scientific references in the development of public relations strategies in every region of Indonesia, which is very rich with various philosophies.Humas Pemerintah Kabupaten Bandung menyadari wilayahnya memiliki banyak potensi kearifan lokal yang beragam, serta memiliki masyarakatnya yang heterogen. Penelitian ini bertujuan menggali dan menganalisis nilai-nilai kearifan lokal dalam pengembangan strategi kehumasan di pemerintahan Kabupaten Bandung provinsi Jawa Barat.  Penelitian ini menggunakan paradigma interpretif (subjektif) konstruktivis melalui pendekatan studi kasus. Hasil penelitian menunjukkan bahwa Pemerintah Kabupaten (Pemkab) Bandung menjalankan pemerintahannya berlandaskan pada kearifal lokal. Humas Pemkab Bandung memanfaatkan kearifan lokal dan potensi wilayahnya untuk mengembangkan strategi humas dalam membangun dan mempertahankan citra positif Kabupaten Bandung.Dampak penelitian ini diharapkan menjadi sumber rujukan ilmiah baru dalam pengembangan strategi kehumasan di setiap daerah Indonesia yang sangat kaya dengan beragam filosofi. 

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