Manifestation of thrombocytopenia in dengue-2-virus-infected mice

Huang, Kuo Yuan; Li, Shu-Yi J.; Chen, Shiour-Ching; Liu, Hsiao-Sheng; Lin, Yee‐Shin; Yeh, Trai Ming; Liu, Ching-Chuan; Lei, Huan‐Yao

doi:10.1099/0022-1317-81-9-2177

Cited by 135 publications

(117 citation statements)

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“…BALB/c mice when infected with different strains of DENV-2 demonstrated variable results (Raut et al 1996, Sierra et al 1999, Huang et al 2000. In our previous studies , BALB/c mice infected by the intraperitoneal route with non-neuroadapted DENV-2, showed cytophatic effects in several organs like lung, liver, cerebellum, and kidney.…”

Section: One Of the Main Difficulties In Studying Dengue Virus Infectmentioning

confidence: 99%

“…However, no infectious model that mimics DHF/DSS has yet been reported (Huang et al 2000). Until now the great majority of mice models of DENV infection deal with suckling or young mice infected by an intracerebral route of inoculation (Nath et al 1983, Raut et al 1996 and with mouse-neuroadapted DENV (Desprès et al 1998, Atrasheuskaya et al 2003.…”

Section: One Of the Main Difficulties In Studying Dengue Virus Infectmentioning

confidence: 99%

“…Until now the great majority of mice models of DENV infection deal with suckling or young mice infected by an intracerebral route of inoculation (Nath et al 1983, Raut et al 1996 and with mouse-neuroadapted DENV (Desprès et al 1998, Atrasheuskaya et al 2003. Response of the animals (clinical symptoms and/or degree of injury) varied according to the mice strain, however the full DHF/DSS manifestations did not seem to occur in standard laboratory mice.BALB/c mice when infected with different strains of DENV-2 demonstrated variable results (Raut et al 1996, Sierra et al 1999, Huang et al 2000. In our previous studies , BALB/c mice infected by the intraperitoneal route with non-neuroadapted DENV-2, showed cytophatic effects in several organs like lung, liver, cerebellum, and kidney.…”

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Morphological studies in a model for dengue-2 virus infection in mice

Barth

Barreto²,

Paes

et al. 2006

Mem. Inst. Oswaldo Cruz

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One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2). Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.Key words: dengue-2 virus -BALB/c mice -liver -viremia -ultrastructure -histopathology Dengue viruses (DENV) are mosquito-borne RNAviruses that are classified serologically into four antigenically distinct types (DENV-1, 2, 3, 4). They infect millions of people in tropical and subtropical regions of the world and may cause a mild to debilitating febrile illness, the classical dengue fever (DF), the dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS). However, the pathogenesis of human dengue infection (DEN) remains not sufficiently known, and no successful vaccine is available as yet (Eckels 1993). The studies on pathogenesis, pharmacodynamics, and prophylaxis of DHF have been hampered due to the lack of a suitable animal model (Bhamarapravati 1993).DENV have been inoculated into numerous species of animals by a variety of routes. Studies on laboratory mice and non-human primates remain the most wellcharacterized models (Cole & Wisseman 1969, Marchette et al. 1973, Boonpucknavig et al. 1981, Hotta et al. 1981a,b, Chaturvedi et al. 1991, Wu et al. 1995.Several studies indicated that mice are a permissive host for DENV (Meiklejhon et al. 1952, Lin et al. 1998, Johnson & Roehrig 1999. However, no infectious model that mimics DHF/DSS has yet been reported (Huang et al. 2000). Until now the great majority of mice models of DENV infection deal with suckling or young mice infected by an intracerebral route of inoculation (Nath et al. 1983, Raut et al. 1996 and with mouse-neuroadapted DENV (Desprès et al. 1998, Atrasheuskaya e...

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Section: One Of the Main Difficulties In Studying Dengue Virus Infectmentioning

confidence: 99%

Section: One Of the Main Difficulties In Studying Dengue Virus Infectmentioning

confidence: 99%

mentioning

confidence: 99%

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Morphological studies in a model for dengue-2 virus infection in mice

Barth

Barreto²,

Paes

et al. 2006

Mem. Inst. Oswaldo Cruz

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“…The most promising model in immunocompetent mice is the A/J mouse strain; it presents with some thrombocytopenia, as seen in humans, and is more sensitive to dengue infection than BALB/c or B6 mice [26]. Intravenous injection of A/J mice with non-mouse-adapted dengue serotype 2 virus induced paraplegia in a subset (55%) of mice on day 8-14 p.i.…”

Section: Pathogenesis In Micementioning

confidence: 99%

“…; increased hematocrit and decreased white blood cell counts were noted with onset of paralysis (not a DF/DHF sign in humans). Antiplatelet antibody was also generated, and increased numbers of splenic natural killer (NK) cells and B cells could be demonstrated after infection [26,27]. However, these mice had to be inoculated with a large quantity of virus (8 log 10 PFU per mouse) intravenously, to induce signs; viremia was low and transient, and could only be detected on day 2 p.i.…”

Section: Pathogenesis In Micementioning

confidence: 99%

Models of dengue virus infection

Bente

Rico-Hesse

2006

Drug Discovery Today: Disease Models

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The need for models of dengue disease has reached a pinnacle as the transmission of this mosquitoborne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models.

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Therapeutic opportunities in dengue infection

Fagundes

Costa

Cisalpino

et al. 2011

Drug Development Research

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Infection by one of the four serotypes of the arthropod-borne dengue virus produces a spectrum of disease manifestations, ranging from asymptomatic to life-threatening Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). During the last several decades, dengue has spread its geographic distribution to become the most common arboviral infection of humans in the subtropical and tropical regions of the world. There is no specific treatment or vaccine approved for human use. This fact, associated with the large number of infected individuals and the lack of markers that indicate which patients will develop severe disease, place an enormous burden on health systems of affected countries. Many efforts have been made to elucidate several aspects of dengue disease, but the pathogenesis of disease is complex and remains unclear. The hallmark of severe dengue disease is a short-lived plasma leakage that is believed to be immune mediated. Understanding the mechanism(s) that underlie the pathogenesis of dengue is critical for the development of safe therapeutics to prevent DHF/DSS. In this review, we highlight potential therapeutic alternatives to treat dengue infection and outline strategies used to develop and research anti-dengue therapies, focusing on in vivo results obtained using the experimental animal models currently available. Within this context, we discuss the therapeutic potential of novel antiviral molecules, either targeting virus-encoded functions or the cellular functions needed for viral replication. In addition, we discuss studies using anti-inflammatory strategies aimed at reducing the exacerbated host response against infection and their potential as promising therapeutic alternatives in severe dengue disease. Drug Dev Res 72:480-500, 2011. Key words: Dengue; therapeutics; animal models; inflammation; antiviral DENGUE: OVERVIEWDengue is caused by a lipid-enveloped virus that contains a single-stranded, positive-sense RNA genome, the Dengue virus (DENV), which exists as four closely related serotypes (DENV-1-4). Dengue virus is a member of the Flaviviridae family and is related to the viruses that cause yellow fever and the Japanese, St. Louis, and West Nile encephalitides. As with other Flaviviruses, they are introduced into the host by an infected vector, Aedes aegypti and A. albopictus DDRPublished online in Wiley Online Library (wileyonlinelibrary.com).

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Manifestation of thrombocytopenia in dengue-2-virus-infected mice

Cited by 135 publications

References 25 publications

Morphological studies in a model for dengue-2 virus infection in mice

Morphological studies in a model for dengue-2 virus infection in mice

Models of dengue virus infection

Therapeutic opportunities in dengue infection

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