Dengue virus therapeutic intervention strategies based on viral, vector and host factors involved in disease pathogenesis

Herrero, Lara J.; Zakhary, Andrew; Gahan, Michelle E.; Nelson, Michelle; Herring, Belinda L.; Hapel, Andrew J.; Keller, P. A.; Obeysekera, Maheshi Prabodani; Chen, Weiqiang; Sheng, Kuo-Ching; Taylor, Adam; Wolf, Stefan; Bettadapura, Jayaram; Broor, Shobha; Dar, Lalit; Mahalingam, Suresh

doi:10.1016/j.pharmthera.2012.10.007

Cited by 46 publications

(28 citation statements)

References 211 publications

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“…Este vírus pode afetar pessoas de todas as idades, incluindo recém-nascidos, crianças, adultos e idosos, causando um espectro de doenças que vai desde a febre da dengue até as formas mais graves de dengue hemorrágica e síndrome do choque da dengue. Os sinais e sintomas incluem febre, dor retro-orbital, dor de cabeça intensa, mialgia, artralgia e manifestações hemorrágicas menores, como petéquias, epistaxe e sangramento gengival 12,13 .…”

Section: Vírus Dengue (Denv)unclassified

Características gerais e epidemiologia dos arbovírus emergentes no Brasil

Lopes

Nozawa

Linhares

2014

Revista Pan-Amazônica de Saúde

168

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RESUMOArbovírus (Arthropod-borne virus) são assim designados pelo fato de parte de seu ciclo de replicação ocorrer nos insetos, podendo ser transmitidos aos seres humanos e outros animais pela picada de artrópodes hematófagos. Dos mais de 545 espécies de arbovírus conhecidos, cerca de 150 causam doenças em humanos. As arboviroses têm representado um grande desafio à saúde pública, devido às mudanças climáticas e ambientais e aos desmatamentos que favorecem a amplificação, a transmissão viral, além da transposição da barreira entre espécies. Neste trabalho de revisão discorremos sobre as características gerais, patogenia e epidemiologia dos arbovírus e das infecções resultantes, que têm emergido ou reemergido no Brasil nas últimas décadas. Pela potencial ameaça que significam à saúde humana no Brasil, os arbovírus mencionados neste trabalho merecem especial atenção no que refere ao estabelecimento/consolidação de programas compulsórios de controle e combate eficazes das doenças em humanos e animais domésticos. Estima-se que haja mais de 545 espécies de arbovírus, dentre as quais, mais de 150 relacionadas com doenças em seres humanos, sendo a maioria zoonótica. São mantidos em ciclo de transmissão entre artrópodes (vetores) e reservatórios vertebrados como principais hospedeiros amplificadores 2,3 . PalavrasAs arboviroses têm se tornado importantes e constantes ameaças em regiões tropicais devido às rápidas mudanças climáticas, desmatamentos, migração populacional, ocupação desordenada de áreas urbanas, precariedade das condições sanitárias que favorecem a amplificação e transmissão viral 1 . São transmitidas pelo sangue de pacientes virêmicos, por insetos hematófagos, o que não deixa de ser uma preocupação na doação de sangue em áreas endêmicas 2 . Casos de transmissão do vírus Oeste do Nilo (WNV) entre seres humanos, por meio de transfusões de sangue e transplante de órgãos, têm sido relatados, entretanto todos os arbovírus que produzem viremia são potencialmente passíveis de desencadearem infecções iatrogênicas 4,5 .O único continente onde os arbovírus não são endêmicos é o Antártico. Estes vírus tendem a ter uma distribuição geográfica e climática restrita, como parte de um subsistema ecológico especial representado pelos vírus, vetores, hospedeiros amplificadores e reservatórios 1 .O Brasil é constituído por uma grande extensão terrestre (pouco mais de 8.500.000 km 2 ), situado em uma área predominantemente tropical, com extensas florestas na Região Amazônica, além de florestas no leste, sudeste e litoral sul. Apresenta também uma

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Section: Vírus Dengue (Denv)unclassified

Características gerais e epidemiologia dos arbovírus emergentes no Brasil

Lopes

Nozawa

Linhares

2014

Revista Pan-Amazônica de Saúde

168

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“…Bagian luar virion immature (diameter 60 nm) terdiri dari protein preM-E (premembran), setelah mengalami pematangan peptida preM akan terlepas sehingga virion hanya memiliki protein E dan diameter berubah menjadi 50 mm. 2 Infeksi DENV menyebabkan penyakit serius di area tropis dan subtropis seperti kawasan Asia Tenggara dengan perkiraan 50 juta infeksi terjadi setiap tahun dan lebih dari 2.5 juta orang beresiko terinfeksi. 3 Infeksi yang disebabkan oleh keempat serotipe DENV terkadang asimtomatis atau dapat juga menunjukkan gejala klinis yang luas, berkisar dari flu ringan/dengue fever (DF), dengue haemorrhagic fever (DHF) yang ditandai dengan demam akut, trombositopenia, netropenia dan pendarahan, hingga bentuk paling bahaya yaitu dengue shock syndrome (DSS).…”

Section: Pendahuluanunclassified

RESPON IMUN SELULER DAN HUMORAL MENCIT YANG DIIMUNISASI KANDIDAT VAKSIN DNA DENGUE BERBASIS GEN preM-E SEROTIPE 4 STRAIN INDONESIA

Urfa¹,

Dewi²,

Sudiro³

2015

MKA

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AbstrakInfeksi virus dengue (DENV) terkadang tanpa gejala atau dapat menunjukkan gejala klinis yang luas, berkisar dari sindrom flu ringan (dengue fever/DF), dengue haemorrhagic fever (DHF), hingga syok hipovolemik (dengue shock syndrome/DSS). Hipotesis yang berkaitan dengan tingkat keparahan infeksi DENV meliputi mekanisme antibody-dependent enhancement (ADE) dan keterlibatan sitokin. Hingga kini, belum ada obat antiviral yang efektif untuk mengeradikasi dan mencegah infeksi DENV, sehingga pencegahan berupa vaksin perlu dikembangkan. Kandidat vaksin DNA berbasis gen preM-E serotipe 4 strain Indonesia yang dikembangkan pada penelitian terdahulu disuntikkan ke mencit ddY, kemudian diuji tantang dengan DENV. Pada hari ke-4 dan ke-21 pascauji tantang, keberadaan sitokin IL-2 dalam serum dideteksi dengan metode ELISA. Serum hari ke-21 digunakan dalam uji ADE menggunakan sel K562. Sel limpa diambil pada hari ke-21 pascauji tantang, kemudian keberadaan IL-2 dan antibodi in vitro dideteksi dengan metode ELISA. Tingkat IL-2 tertinggi terdapat pada serum hari ke-4 pada kelompok mencit yang tidak diimunisasi namun diuji tantang, yaitu sebesar 69,83 pg/ml. Konsentrasi IL-2 terendah ditunjukkan oleh kelompok mencit yang diimunisasi namun tidak diuji tantang, yaitu 0 pg/ml. Pengukuran IL-2 pada serum dan supernatan sel limpa hari ke-21 tidak mendapatkan konsentrasi IL-2. Titer antibodi tertinggi terdapat pada kelompok sel limpa mencit yang diimunisasi, diuji tantang, dan diinduksi in vitro dengan DENV. Hasil uji ADE menunjukkan tingkat pengenceran serum berpengaruh terhadap jumlah sel yang terinfeksi oleh DENV, namun tidak ditemukan kondisi netralisasi dan enhancing. Berdasarkan metode yang digunakan, kandidat vaksin DNA tersebut dapat memicu respon imun seluler dan humoral. Kata kunci: respon imun, vaksin DNA, virus dengue, gen preM-E, IL-2 AbstractDengue virus (DENV) infection can be asymptomatic or cause wide range of clinical symptoms, from mild febrille ilness (dengue fever/DF), dengue haemorrhagic fever (DHF), to hipovolemic shock (dengue shock syndrome/DSS). Hypotheses related to the severity of DENV infection mechanisms including antibody-dependent enhancement (ADE) and cytokines involvement. Until now, there are no effective antiviral drugs can eradicate and prevent DENV infection, therefore the development of vaccines is the alternative. DNA vaccine candidate preM-E serotype 4 strain of Indonesia which was developed in previous studies injected into ddY mice, then challenge with DENV. At day 4 and 21 post-challenge, serum was taken to detect the presence of cytokines IL-2 using ELISA method. Day 21 serum used in the antibody-dependent enhancement (ADE) assay using K562 cell line. Splenocytes were taken at day 21 post-challenge to measure the presence of IL-2 and in vitro antibody using ELISA method. Measurement of IL-2 on day 4 serum produced the highest levels of IL-2 (69.83 pg/ml) in the group of non-immunized, challenged mice, whereas the lowest concentration (0 pg/ml) shown by the group of immunized, non-challe...

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“…Inhibition of the viral entry into the host cell via binding of viral E protein to heparin sulfate during early infection is normally the first point of intervention (34). (34). It is envisaged from studies conducted using Phyllanthus that it has a putative role in reducing viral load in mosquitoes.…”

Section: Antiviral Activity Of Phyllanthusmentioning

confidence: 99%

“…However, understanding of the molecular mechanisms behind the dengue virus life cycle and elucidation of the specific functions for each dengue viral proteins has allowed the design of novel antiviral targets. Some of these potential therapeutic intervention targets include viral entry, viral RNA polymerase/ methyltransferase, nucleotide synthesis, viral serine protease, α-glucosidases and kinases (34). Nonetheless, plants that are rich in bioactive components remain the basis for these novel antiviral compounds.…”

Section: Introduction On Denguementioning

confidence: 99%

Phyllanthus Sp a Local Plant With Multiple Medicinal Properties

Sd¹,

Yq²,

Sh³

2014

JUMMEC

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The plants of the genus Phyllanthus (Euphorbiaceae) are distributed in most tropical and subtropical regions of world. This plant has been long used as a traditional medicine to treat problems such as stomach, intestinal infections, kidney and urinary bladder disturbances, diabetes, and hepatitis B. There has been considerable interest in these plants in recent years. This review discusses the antiviral and anticancer aspects of Phyllanthus species. Scientific studies have demonstrated that extracts and purified isolated compounds (flavonoids, lignans, phenols, and terpenes) obtained from these plants possess antiviral effects against herpes simplex (HSV) and dengue virus infections (DENV). These observations are associated with the disruption of essential proteins needed during viral cycle, thus halting the viral replication. In addition, the Phyllanthus species have also been shown to exert inhibitory effects against selected cancers types. In these studies anti-proliferative, anti-metastatic, anti-angiogenic effects and induced apoptosis of human cancers cell lines were observed. These may be explained by the disruption of multiple survival pathways and differential protein expression. CONLCUSION:As a conclusion, tThe Phyllanthus plant possesses multiple medicinal properties, including antiviral and anticancer activities which may potentially be used as a medicinal source for many disease locally.

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Dengue virus therapeutic intervention strategies based on viral, vector and host factors involved in disease pathogenesis

Cited by 46 publications

References 211 publications

Características gerais e epidemiologia dos arbovírus emergentes no Brasil

Características gerais e epidemiologia dos arbovírus emergentes no Brasil

RESPON IMUN SELULER DAN HUMORAL MENCIT YANG DIIMUNISASI KANDIDAT VAKSIN DNA DENGUE BERBASIS GEN preM-E SEROTIPE 4 STRAIN INDONESIA

Phyllanthus Sp a Local Plant With Multiple Medicinal Properties

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