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Apoptosis and dengue

Gisa Gerold, Janina Bruening, Bettina Weigel, Thomas Pietschmann
Protein-protein interactions govern biological functions in cells, in the extracellular milieu and at the border between cells and extracellular space. Viruses are small intracellular parasites and thus rely on protein interactions to produce progeny inside host cells and to spread from cell to cell. Usage of host proteins by viruses can have severe consequences e.g. apoptosis, metabolic disequilibria or altered cell proliferation and mobility. Understanding protein interactions during virus infection can thus educate us on viral infection and pathogenesis mechanisms...
January 11, 2017: Molecular & Cellular Proteomics: MCP
S Sakinah, Sivan Padma Priya, Sharmilah Kumari, Fatin Amira, Poorani K, Hiba Alsaeedy, Mok Pooi Ling, Hui-Yee Chee, Akon Higuchi, Abdullah A Alarfaj, Murugan A Munusamy, Kadarkarai Murugan, Che Norma Mat Taib, Palanisamy Arulselvan, Mariappan Rajan, Vasantha Kumari Neela, Rukman Awang Hamat, Giovanni Benelli, S Suresh Kumar
In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces...
November 23, 2016: Tissue & Cell
Yuan Tian, Alessandro Sette, Daniela Weiskopf
Dengue virus (DENV) has spread through most tropical and subtropical areas of the world and represents a serious public health problem. The control of DENV infection has not yet been fully successful due to lack of effective therapeutics or vaccines. Nevertheless, a better understanding of the immune responses against DENV infection may reveal new strategies for eliciting and improving antiviral immunity. T cells provide protective immunity against various viral infections by generating effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring pathogens...
2016: Frontiers in Immunology
João Miguel Freire, Inês Rego de Figueiredo, Javier Valle, Ana Salomé Veiga, David Andreu, Francisco J Enguita, Miguel A R B Castanho
Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by a single gene mutation, a reciprocal translocation that originates the Bcr-Abl gene with constitutive tyrosine kinase activity. As a monogenic disease, it is an optimum target for RNA silencing therapy. We developed a siRNA-based therapeutic approach in which the siRNA is delivered by pepM or pepR, two cell-penetrating peptides (CPPs) derived from the dengue virus capsid protein. These peptides have a dual role: siRNA delivery into cells and direct action as bioportides, i...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
San Suwanmanee, Natthanej Luplertlop
Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies...
January 2017: Viral Immunology
Nicholas L Bayless, Rachel S Greenberg, Tomek Swigut, Joanna Wysocka, Catherine A Blish
Zika virus (ZIKV) infection during pregnancy is linked to microcephaly, which is attributed to infection of developing brain structures. ZIKV infects neural progenitor cells in vitro, though its effects on other developmentally relevant stem cell populations, including cranial neural crest cells (CNCCs), have not been assessed. CNCCs give rise to most cranial bones and exert paracrine effects on the developing brain. Here, we report that CNCCs are productively infected by ZIKV, but not by the related dengue virus...
October 12, 2016: Cell Host & Microbe
Jaime E Castellanos, José I Neissa, Sigrid J Camacho
INTRODUCTION: Dengue is a human disease caused by a virus with the same name, which is transmitted by the bite of Aedes mosquitoes. The infection has a wide range of clinical presentations ranging from asymptomatic to fatal cases, with the pediatric population being the most susceptible. According to the new classification of the disease, the neurological manifestations are considered a criterion for the diagnosis of severe dengue.  OBJECTIVE: To evaluate the possible mechanisms involved in the onset of neurological signs in a cell line of human neurons as a model of infection with dengue virus type 2 (DENV-2)...
April 15, 2016: Biomédica: Revista del Instituto Nacional de Salud
Abel Trujillo-Ocampo, Febe Elena Cázares-Raga, Antonio Celestino-Montes, Leticia Cortés-Martínez, Mario H Rodríguez, Fidel de la Cruz Hernández-Hernández
The 14-3-3 proteins are evolutionarily conserved acidic proteins that form a family with several isoforms in many cell types of plants and animals. In invertebrates, including dipteran and lepidopteran insects, only two isoforms have been reported. 14-3-3 proteins are scaffold molecules that form homo- or heterodimeric complexes, acting as molecular adaptors mediating phosphorylation-dependent interactions with signaling molecules involved in immunity, cell differentiation, cell cycle, proliferation, apoptosis, and cancer...
November 2016: Archives of Insect Biochemistry and Physiology
Feiran Zhang, Christy Hammack, Sarah C Ogden, Yichen Cheng, Emily M Lee, Zhexing Wen, Xuyu Qian, Ha Nam Nguyen, Yujing Li, Bing Yao, Miao Xu, Tianlei Xu, Li Chen, Zhiqin Wang, Hao Feng, Wei-Kai Huang, Ki-Jun Yoon, Chao Shan, Luoxiu Huang, Zhaohui Qin, Kimberly M Christian, Pei-Yong Shi, Mingjiang Xu, Menghang Xia, Wei Zheng, Hao Wu, Hongjun Song, Hengli Tang, Guo-Li Ming, Peng Jin
Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function is unclear. Here we systematically profiled transcriptomes of human neural progenitor cells exposed to Asian ZIKV(C), African ZIKV(M), and dengue virus (DENV). In contrast to the robust global transcriptome changes induced by DENV, ZIKV has a more selective and larger impact on expression of genes involved in DNA replication and repair. While overall expression profiles are similar, ZIKV(C), but not ZIKV(M), induces upregulation of viral response genes and TP53...
October 14, 2016: Nucleic Acids Research
Jianshe Lang, Daniel Vera, Yichen Cheng, Hengli Tang
The development of dengue antivirals and vaccine has been hampered by the incomplete understanding of molecular mechanisms of dengue virus (DENV) infection and pathology, partly due to the limited suitable cell culture or animal models that can capture the comprehensive cellular changes induced by DENV. In this study, we differentiated human pluripotent stem cells (hPSCs) into hepatocytes, one of the target cells of DENV, to investigate various aspects of DENV-hepatocyte interaction. hPSC-derived hepatocyte-like cells (HLCs) supported persistent and productive DENV infection...
September 13, 2016: Stem Cell Reports
Jean-Baptiste Brault, Cécile Khou, Justine Basset, Laure Coquand, Vincent Fraisier, Marie-Pascale Frenkiel, Bruno Goud, Jean-Claude Manuguerra, Nathalie Pardigon, Alexandre D Baffet
The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV), can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV) and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4)...
August 2016: EBioMedicine
Matthew W Eng, Madeleine N van Zuylen, David W Severson
The mosquito Aedes aegypti is the primary urban vector for dengue virus (DENV) worldwide. Insight into interactions occurring between host and pathogen is important in understanding what factors contribute to vector competence. However, many of the molecular mechanisms for vector competence remain unknown. Our previous global transcriptional analysis suggested that differential expression of apoptotic proteins is involved in determining refractoriness vs susceptibility to DENV-2 infection in Ae. aegypti females following a DENV-infected blood meal...
September 2016: Insect Biochemistry and Molecular Biology
Lara C Mario, Jéssica Borghesi, Wilson T Crivellari-Damasceno, Phelipe O Favaron, Ana Claudia O Carreira, Sonia E A L Will, Durvanei A Maria, Maria A Miglino
According to the World Health Organization, 2015 registered more than 1.206.172 cases of Dengue in the Americas. Recently, the Aedes aegypti has been not only related to Dengue, but also with cases of Zika virus and Chikungunya. Due to its epidemiological importance, this study characterized the morphology of the embryonated eggs of A. aegypti and provided a protocol to culture stem cells from eggs and digestive tract of fourth instar larvae in order to examine cell biology and expression of markers in these vectors...
October 2016: Tissue & Cell
Andrea Troupin, Berlin Londono-Renteria, Michael J Conway, Erin Cloherty, Samuel Jameson, Stephen Higgs, Dana L Vanlandingham, Erol Fikrig, Tonya M Colpitts
BACKGROUND: Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated...
September 2016: Biochimica et Biophysica Acta
Hua Pei, Li Zuo, Jing Ma, Lili Cui, Fangfang Yu, Yingzi Lin
A cell model is critical for studying the molecular mechanisms of dengue virus 2 (DENV-2) invasions and cell bioactivity can be easily affected by the substrate matrix. Tissue culture plastic (TCP) and polyacrylamide hydrogel (PAMH) are two kinds of matrices widely used for cells. The effects of different matrices on the cultured cells with DENV-2 invasion remain unknown. To address the issue, the effects of TCP and PAMH were explored in primary human umbilical vein endothelial cells (HUVECs) with DENV-2 invasion...
July 2016: Journal of Medical Virology
Federico Perdomo-Celis, Doris M Salgado, Diana M Castañeda, Carlos F Narváez
Cryopreserved peripheral blood mononuclear cells (PBMCs) are widely used in studies of dengue. In this disease, elevated frequency of apoptotic PBMCs has been described, and molecules, such as soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL), are involved. This effect of dengue could affect the efficiency of PBMCs cryopreservation. Here, we evaluate viability (trypan blue dye exclusion and amine-reactive dye staining) and functionality (frequency of interferon [IFN]-γ producing T cells after polyclonal stimulation) of fresh and cryopreserved PBMCs from children with dengue (in acute and convalescence phase), children with other febrile illnesses, and healthy children as controls...
March 9, 2016: Clinical and Vaccine Immunology: CVI
Tooba Naz Shamsi, Romana Parveen, Sadaf Fatima
This review describes Protease Inhibitors (PIs) which target or inhibit proteases, protein digesting enzymes. These proteases play a crucial task in many biological events including digestion, blood coagulation, apoptosis etc. Regardless of their crucial roles, they need to be checked regularly by PIs as their excess may possibly damage host organism. On basis of amino acid composition of PIs where Protease-PI enzymatic reactions occur i.e. serine, cysteine, and aspartic acid, they are classified. Nowadays, various PIs are being worked upon to fight various parasitic or viral diseases including malaria, schistosomiasis, colds, flu', dengue etc...
October 2016: International Journal of Biological Macromolecules
Gopinathan Pillai Sreekanth, Aporn Chuncharunee, Aunchalee Sirimontaporn, Jutatip Panaampon, Sansanee Noisakran, Pa-Thai Yenchitsomanus, Thawornchai Limjindaporn
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...
2016: PloS One
Rollie J Clem
A relatively small number of mosquito species transmit arboviruses such as dengue, yellow fever, chikungunya and West Nile viruses to hundreds of millions of people each year, yet we still lack a thorough understanding of the molecular factors that determine vector competence. Apoptosis has been shown to be an important factor in determining the outcome of virus infection for many viruses. However, until recently, it was not clear whether apoptosis plays a role in determining the outcome of arbovirus infections in mosquitoes...
May 2016: Journal of General Virology
Wang Yang, Huacheng Yan, Yuling Ma, Tiantian Yu, Hongxia Guo, Yuchan Kuang, Ruiwen Ren, Jintao Li
The available evidence suggests that dengue virus-specific T lymphocytes and cytokine storm play a pivotal role in the immunopathogenesis of plasma leakage. Investigations are underway to identify the immune profiles associated with increased or decreased risk for severe disease. In this study, CD14+ cells from the peripheral blood mononuclear cells (PBMCs) of patients who recovered from DENV-1 infection were infected with DENV-1 or DENV-2 and co-cultured with memory T cells. We found that secondary infection with DENV-2 suppresses the cell reproductive capacity but forms more cell clones and more functional cells to produce more proinflammatory factors (IFN-γ, TNF-α, IL-6, IL-8, IL-12 and IL-17) and less regulatory cytokines (IL-10, TGF-β) which results in higher viral replication compared to secondary infection with DENV-1...
March 2016: Immunobiology
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