Replication of Marburg virus in human endothelial cells. A possible mechanism for the development of viral hemorrhagic disease.

Schnittler, Hans-Joachim; Mahner, F; Drenckhahn, Detlev; Klenk, Hans‐Dieter; Feldmann, Heinz

doi:10.1172/jci116329

Cited by 113 publications

(73 citation statements)

References 24 publications

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“…Several cell lines (E6, MA 104 and Vero), which do not express the ASGP-R, support replication of MBG. Furthermore, MBG is able to infect human endothelial cells which also lack the ASGP-R (Schnittler et al, 1993). For this reason it has to be postulated that, in addition to the ASGP-R, other receptors may mediate entry of MBG into cells.…”

Section: Discussionmentioning

confidence: 99%

The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus

Becker

Spiess²,

Klenk³

1995

Journal of General Virology

160

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The liver is one of the main target organs of Marburg virus (MBG), a filovirus causing severe haemorrhagic fever with a high fatality rate in humans and non-human primates. MBG grown in certain cells does not contain neuraminic acid, but has terminal galactose on its surface glycoprotein. This observation indicated that the asialoglycoprotein receptor (ASGP-R) of hepatocytes may serve as a receptor for MBG in the liver. Binding studies revealed that the attachment of MBG to ASGP-R-expressing HepG2 cells, but not to ASGP-R-negative E6 Vero cells, has the characteristics ofligand binding to the ASGP-R: binding is dependent on calcium and is inhibited by excess asialofetuin and by anti-ASGP-R antiserum. Asialofetuin and the specific antiserum also inhibited MBG infection of HepG2 cells. In addition, it was shown that expression of ASGP-R cDNA in NIH 3T3 cells enhanced the susceptibility of these cells to MBG infection 4'5-fold. Interaction of MBG with the hepatic ASGP-R could thus explain the marked hepatotropism of the virus.

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Section: Discussionmentioning

confidence: 99%

The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus

Becker

Spiess²,

Klenk³

1995

Journal of General Virology

160

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“…Yang et al (1998) suggested that EBO infection of endothelial cells may cause the hemorrhagic diapedesis in guinea pigs. Studies showing infection of endothelial cells by MBG and EBO viruses in vitro (Geisbert and Jaax, 1998;Schnittler et al, 1993) and filovirusinfected endothelial cells in postmortem tissues from humans and nonhuman primates (Baskerville et al, 1985;Davis et al, 1997;Geisbert et al, 1992;Jaax et al, 1996;Zaki and Goldsmith, 1999) have been used to support these views. More recent studies employing serially collected rodent and monkey tissues show that endothelial cell infection is, in fact, primarily associated with later stages of infection (Connolly et al, 1999;Ryabchikova et al, 1999).…”

Section: Geisbert Et Almentioning

confidence: 99%

Apoptosis Induced In Vitro and In Vivo During Infection by Ebola and Marburg Viruses

Geisbert

Hensley

Gibb

et al. 2000

Laboratory Investigation

289

254

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SUMMARY:Induction of apoptosis has been documented during infection with a number of different viruses. In this study, we used transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling to investigate the effects of Ebola and Marburg viruses on apoptosis of different cell populations during in vitro and in vivo infections. Tissues from 18 filovirus-infected nonhuman primates killed in extremis were evaluated. Apoptotic lymphocytes were seen in all tissues examined. Filoviral replication occurred in cells of the mononuclear phagocyte system and other well-documented cellular targets by TEM and immunohistochemistry, but there was no evidence of replication in lymphocytes. With the exception of intracytoplasmic viral inclusions, filovirus-infected cells were morphologically normal or necrotic, but did not exhibit ultrastructural changes characteristic of apoptosis. In lymph nodes, filoviral antigen was co-localized with apoptotic lymphocytes. Examination of cell populations in lymph nodes showed increased numbers of macrophages and concomitant depletion of CD8 ϩ T cells and plasma cells in filovirus-infected animals. This depletion was particularly striking in animals infected with the Zaire subtype of Ebola virus. In addition, apoptosis was demonstrated in vitro in lymphocytes of filovirus-infected human peripheral blood mononuclear cells by TEM. These findings suggest that lymphopenia and lymphoid depletion associated with filoviral infections result from lymphocyte apoptosis induced by a number of factors that may include release of various chemical mediators from filovirus-infected or activated cells, damage to the fibroblastic reticular cell conduit system, and possibly stimulation by a viral protein. (Lab Invest 2000, 80:171-186).I nfections with filoviruses cause severe and often fatal hemorrhagic disease in humans and nonhuman primates, killing up to 90% of infected individuals. Ebola (EBO) and Marburg (MBG) viruses comprise the family Filoviridae (Murphy et al, 1995). The EBO species consists of the Zaire and Sudan subtypes first isolated during separate outbreaks in 1976, the Reston subtype initially isolated from monkeys imported from the Philippines to the United States in 1989, and the Cô te d'Ivoire subtype discovered in the Tai Forest of the Ivory Coast in 1994. The recent re-emergence of EBO subtype Zaire (EBO-Z) in former Zaire and Gabon, and subtype Reston (EBO-R) in the United States, are but the last of a succession of filoviral outbreaks that have occurred sporadically since the initial zoonotic outbreak of MBG in 1967. Although outbreaks have been self-limiting, the lack of proven effective prophylactic or therapeutic regimens to treat filoviral infections has heightened concerns about the public health threat of these pathogens.The factors contributing to the development of severe lesions in EBO and MBG hemorrhagic fevers are unknown. Filoviral infections of humans and nonhuman primates are characterized by a failure o...

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“…Unlike the filoviruses, Marburg and Ebola, that destroy vascular endothelial cells in culture [Schnittler et al, 1993;Feldmann et al, 1996;Yang et al, 1998;Baize et al, 1999], arenaviruses like Lassa fever virus do not destroy cultured endothelial cells, but do diminish their capacity to express chemokines [Fisher-Hoch et al, 1987;Schnittler et al, 1993;Lukashevich et al, 1999]. Also unlike Ebola and Marburg hemorrhagic disease, Lassa fever disease does not cause an increase in fibrinogen breakdown products or diffuse intravascular coagulation (DIC) [Fisher-Hoch et al, 1988].…”

Section: Subclinical Transient Mucosal Infection Of Rhesus Macaques Bmentioning

confidence: 99%

Hemorrhagic fever occurs after intravenous, but not after intragastric, inoculation of rhesus macaques with lymphocytic choriomeningitis virus

Lukashevich

Djavani

Rodas

et al. 2002

Journal of Medical Virology

100

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Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriome-ningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.-inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease.

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Replication of Marburg virus in human endothelial cells. A possible mechanism for the development of viral hemorrhagic disease.

Abstract: Marburg and Ebola

Cited by 113 publications

References 24 publications

The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus

The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus

Apoptosis Induced In Vitro and In Vivo During Infection by Ebola and Marburg Viruses

Hemorrhagic fever occurs after intravenous, but not after intragastric, inoculation of rhesus macaques with lymphocytic choriomeningitis virus

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