Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection

Atrasheuskaya, Alena; Petzelbauer, Peter; Fredeking, Terry; Ignatyev, G. M.

doi:10.1111/j.1574-695x.2003.tb00646.x

Cited by 127 publications

(96 citation statements)

References 34 publications

(44 reference statements)

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“…In necropsy studies of DHF cases, hemorrhagic foci, mononuclear cell infiltrate around the portal space, with focal vacuolization in the cytoplasm of hepatocytes were observed in the liver tissue (Fresh et al 1969, Rosen et al 1989, Innis 1995, Bhamarapravati 1997, Couverland et al 1999, Oliveira et al 2005. When BALB/c mice were infected with neuroadapted DENV, serious injuries in the hepatic tissue have been observed (Atrasheuskaya et al 2003). In the present study, the injury in hepatic tissue of BALB/c mice infected with non-neuroadapted DENV-2 was caracterized by histological and ultrastructural observations, and in addition by biochemical and morphometrical tests.…”

Section: Discussionmentioning

confidence: 73%

“…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. 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.…”

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

confidence: 99%

“…The majority of models use suckling or young mice inoculated with a neuroadapted mouse DENV strain (Nath et al 1983, Raut et al 1996. Susceptibility of BALB/c mice infected by the intraperitoneal route with a neuroadapted mouse DENV strain has been demonstrated (Atrasheuskaya et al 2003). The injuries observed in our experimental mice model when mice were infected Morphological aspects of lung tissue of BALB/c mice infected with dengue viruses serotype 2. by the intraperitoneal route with a non-neuroadapted DENV-2 are mild when compared with other animal models.…”

mentioning

confidence: 99%

“…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. The virus was ultrastructurally identified using electron microscopy and demonstrated by immunofluorescence techniques in C6/36 mosquito cell cultures, inoculated with the supernate of liver tissue macerate from mice after 48 h of infection.BALB/c mice infected by the intraperitoneal route with a DENV-2 strain adapted to the brain of suckling mice, demonstrated anemia, thrombocitopenia, preterminal paralysis, and shock (Atrasheuskaya et al 2003). The analysis of the liver tissue showed extensive cell cytopathic effects as vacuolization and intracellular edema; the architecture of the hepatic lobules was partially destroyed; sinusoids were partially collapsed; only a minimal and diffusely distributed mononuclear inflammatory infiltrate was visible; blood vessels were dilated; In humans, DENV has been frequently isolated from the liver, and the antigens have been detected in Kupffer cells and hepatocytes (Rosen et al 1989, Bhamarapravati 1997, Couverland et al 1999.…”

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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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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: Discussionmentioning

confidence: 73%

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

confidence: 99%

mentioning

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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“…44 The nucleic acid sequence of a portion for E and NS1 genes of DENV strain P23085 has been deposited previously at GenBank under accession No. AY927231.1.…”

Section: Virusmentioning

confidence: 99%

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

Renneson¹,

Guabiraba²,

Maillet³

et al. 2011

The American Journal of Pathology

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Dengue virus (DENV), a member of the mosquitoborne flaviviruses, is a serious public health problem in many tropical countries. We assessed the in vivo physiologic contribution of invariant natural killer T (iNKT) cells, a population of nonconventional lipidreactive ␣␤ T lymphocytes, to the host response during experimental DENV infection. We used a mouseadapted DENV serotype 2 strain that causes a disease that resembles severe dengue in humans. On DENV challenge, splenic and hepatic iNKT cells became activated insofar as CD69 and Fas ligand up-regulation and interferon-␥ production. C57BL/6 mice deficient in iNKT cells (J␣18 ؊/؊ ) were more resistant to lethal infection than were wild-type animals, and the phe Dengue virus (DENV), a flavivirus of the Flaviviridae family, is a serious public health problem in tropical and subtropical areas. In the last 60 years, the incidence, distribution, and clinical severity of dengue-related diseases have increased dramatically. 1,2 There are an estimated 50 million to 100 million DENV infections each year, of which approximately 500,000 are severe dengue hemorrhagic fever, and 24,000 result in death. 2,3 DENV is a single-stranded RNA virus that is transmitted to humans by Aedes mosquitoes, primarily Aedes aegypti. Infection with any of the four serotypes of DENV results in clinical symptoms that range from classic dengue fever to severe dengue hemorrhagic fever and shock syndrome, as defined by the World Health Organization. 4 Severe forms are life-threatening and are characterized by hemorrhagic manifestations, hemoconcentration, thrombocytopenia, and increased vascular permeability. 1,5-10 Despite growing public health concerns, currently there is no vaccine and no specific theraSupported in part by the

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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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Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection

Cited by 127 publications

References 34 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

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

Therapeutic opportunities in dengue infection

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