Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation

Rajmane, Yogesh; Shaikh, Sameer; Basha, Khalander; Reddy, G.E.C. Vidyadhar; Nair, Soumya; Kamath, Sangita Pai; Sreejesh, Greeshma; Rao, Harinarayana; Ramana, Venkata; Kumar, Anil

doi:10.1016/j.virusres.2013.01.002

Cited by 5 publications

(4 citation statements)

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“…The WBC and platelet counts of the DENV-infected mice were reduced, suggesting leucopenia and thrombocytopenia, respectively, which are commonly seen in patients infected with DENV. These results are consistent with other models of DENV infection [ 63 – 65 ] and are similar to the symptoms in C57BL/6 mice [ 66 ] and human patients [ 67 ]. Although SB203580 improves the hematological profile, the levels of leucopenia and thrombocytopenia in the DENV-infected mice are still decreased relative to those in uninfected mice, similar to the results obtained with the chemical inhibitor of ERK1/2, FR180204 [ 48 ].…”

Section: Discussionsupporting

confidence: 91%

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

et al. 2016

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Dengue virus (DENV) infection causes organ injuries, and the liver is one of the most important sites of DENV infection, where viral replication generates a high viral load. The molecular mechanism of DENV-induced liver injury is still under investigation. The mitogen activated protein kinases (MAPKs), including p38 MAPK, have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo role of p38 MAPK in DENV-induced liver injury is not fully understood. In this study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse model of DENV infection. Both the hematological parameters, leucopenia and thrombocytopenia, were improved by SB203580 treatment and liver transaminases and histopathology were also improved. We used a real-time PCR microarray to profile the expression of apoptosis-related genes. Tumor necrosis factor α, caspase 9, caspase 8, and caspase 3 proteins were significantly lower in the SB203580-treated DENV-infected mice than that in the infected control mice. Increased expressions of cytokines including TNF-α, IL-6 and IL-10, and chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 treatment. DENV infection induced the phosphorylation of p38MAPK, and its downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did not decrease the phosphorylation of p38 MAPK, but it significantly reduced the phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the downstream signals to p38 MAPK and reduces DENV-induced liver injury.

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Section: Discussionsupporting

confidence: 91%

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

et al. 2016

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“…*** P < 0.0001 compared to Untreated control. H, HiPerfect. been shown to be more virulent than the other three serotypes in mice (Schul et al, 2007;Rajmane et al, 2013).…”

Section: D2c Protein As An Sirna Carrier For Anti Dengue Viral Applicmentioning

confidence: 99%

“…The source and early passage history of representatives of the four serotypes of DENV have been described earlier (Rajmane et al, 2013). Passaging of DENV serotypes 1, 3 and 4 in infant AG129 mouse brain (2 passages), followed by serial spleen to spleen passaging in adult AG129 mice (3 passages), and C6/36 cell line amplification (3 passages) resulted in all serotypes having a high plaque titre of 10 8 PFU/ml.…”

Section: Cell Lines and Virusesmentioning

confidence: 99%

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

Kumar

Reddy

Rajmane

et al. 2015

Journal of Biotechnology

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“…As diferenças entre os grupos inoculados para os parâmetros avaliados foram determinadas por analise de Teste t, onde ** indica p < 0,01 em comparação ao grupo de animais controle. (BARROS et al, 2015;COSTA et al, 2011;PAES et al, 2005;RAJMANE et al, 2013;TAN et al, 2010;YAMANAKA;KONISHI, 2009). No entanto, as condições experimentais se mostraram distintas em função de diferentes variáveis, isto é, isolado ou cepa utilizada, linhagens de animais imunodeficientes, quantidades de vírus inoculada ou, até mesmo, a incorporação de adjuvantes (BARROS et al, 2015;GUABIRABA, 2013;PAES et al, 2005;RAJMANE et al, 2013;TAN et al, 2010;WILLIAMS et al, 2009;YAMANAKA;KONISHI, 2009).…”

Section: Acompanhamentounclassified

Desenvolvimento de modelo experimental de infecção pelo vírus da dengue em camundongos.

Pereira¹

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Este trabalho é fruto de muito trabalho, esforço e dedicação não apenas por mim, mas também por muitas parcerias e colaborações. Meu agradecimento sincero: Ao Profº Dr. Luís Carlos pela orientação, pelos votos de confiança e ensinamentos, que possibilitaram o desenvolvimento do trabalho. Ao pesquisador Dr. Jaime Henrique Amorim, pelos ensinamentos teóricopráticos básicos necessários para o início do trabalho, pelo apoio à ideia inicial do trabalho e auxilio para que ganhasse forma. À colaboração da pesquisadora Dra. Camila Romano e ao Felipe Scassi Salvador pelas ideias e discussão das mesmas, pelo auxílio, pela determinação e dedicação. À Dra. Viviane Fongaro Botosso e à Dra. Virgínia Barreto Moreira (Butantã) pelo auxílio na obtenção de camundongos. À equipe e ao Profº Edison Durigon, à pesquisadora Daniele Bruna Leal de Oliveira (Dani Durigon), ao técnico de laboratório Luciano Matsumiya Thomazelli e ao aluno de iniciação cientifica Flávio Mesquita pela colaboração, por me receberem de braços abertos em seu laboratório, por disponibilizarem do tempo e do laboratório onde parte dos experimentos foram feitos, pelos ensinamentos, pela compreensão, paciência, dedicação e momentos de descontração. À professora Rita pelo voto de confiança ao abrir as portas do laboratório para mim. Aos amigos e técnicos do LDV: Eduardo Gimenes e Carolina Berteli, pela amizade e por sempre mais do que auxiliarem no que fosse preciso e da melhor forma possível.

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Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation

Cited by 5 publications

References 58 publications

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

Desenvolvimento de modelo experimental de infecção pelo vírus da dengue em camundongos.

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