Pathogenesis of Experimental Ebola Zaire Virus Infection in BALB/c Mice

Gibb, T.R.; Bray, Mike; Geisbert, Thomas W.; Steele, Keith; Kell, Wayne; Davis, Kelly J.; Jaax, Nancy K.

doi:10.1053/jcpa.2001.0502

Cited by 137 publications

(115 citation statements)

References 18 publications

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“…Routine light microscopic studies of placebo-treated mice revealed lysis of MPS cells throughout marginal zones of the spleen, infection of Kupffer cells throughout the liver and multifocal hepatocellular necrosis, as previously described (Gibb et al, 2001). By contrast, mice treated on day 0 or 1 showed minimal evidence of injury to the liver or spleen, while those treated on day 2 showed lysis of MPS cells within the marginal zones of the spleen and occasional foci of hepatocellular necrosis.…”

Section: Pathology Immunohistochemistry and Electron Microscopysupporting

confidence: 78%

“…Earlier studies in BALB/c mice infected with mouse-adapted virus showed that viral replication cannot be detected in tissues on day 1 postinfection, but can be found in a moderate number of MPS cells of the lymph nodes and the spleen on day 2 (Gibb et al, 2001). By day 3, innumerable MPS cells in lymphoid tissues and the liver are infected, as are large number of hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

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3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice

et al. 2002

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3-Deazaneplanocin A, an analog of adenosine, is a potent inhibitor of Ebola virus replication. A single dose early in infection prevents illness and death in Ebola virus-infected mice. The ability of this and similar compounds to block both RNA and DNA viruses has been attributed to the inhibition of a cellular enzyme, S-adenosylhomocysteine hydrolase (SAH), indirectly resulting in reduced methylation of the 5% cap of viral messenger RNA. However, we found that the protective effect of the drug resulted from massively increased production of interferon-a in Ebola-infected, but not uninfected mice. Peak interferon levels increased with the extent of disease at the time of treatment, indicating that production was boosted only in virus-infected cells. Ebola virus has been shown to suppress innate antiviral mechanisms of the type I interferon response. 3-Deazaneplanocin A appears to reverse such suppression, restricting viral dissemination. Further development should focus on identifying adenosine analogues that produce a similar effect in Ebola virus-infected primates. Published by Elsevier Science B.V.

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Section: Pathology Immunohistochemistry and Electron Microscopysupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice

et al. 2002

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“…These include viral glycoprotein-mediated cytotoxicity, dysregulation of the coagulation cascade due to the production of tissue factor, and the production of proinflammatory cytokines (10,16,17,51,54,57). General immunosuppression also appears to be a characteristic of EBOV infection (7,46), and inhibition of dendritic cell and macrophage activation are among the possible mechanisms of this suppression (5,18,38). These processes likely occur as a result of active viral replication.…”

Section: Ebola Virus (Ebov) and Marburg Virus Comprise The Familymentioning

confidence: 99%

Ebola Virus VP24 Proteins Inhibit the Interaction of NPI-1 Subfamily Karyopherin α Proteins with Activated STAT1

Reid

Valmas

Martinez

et al. 2007

J Virol

224

249

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The Zaire ebolavirus protein VP24 was previously demonstrated to inhibit alpha/beta interferon (IFN-␣/␤)-and IFN-␥-induced nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1) and to inhibit IFN-␣/␤-and IFN-␥-induced gene expression. These properties correlated with the ability of VP24 to interact with the nuclear localization signal receptor for PY-STAT1, karyopherin ␣1. Here, VP24 is demonstrated to interact not only with overexpressed but also with endogenous karyopherin ␣1. Mutational analysis demonstrated that VP24 binds within the PY-STAT1 binding region located in the C terminus of karyopherin ␣1. In addition, VP24 was found to inhibit PY-STAT1 binding to both overexpressed and endogenous karyopherin ␣1. We assessed the binding of both PY-STAT1 and the VP24 proteins from Zaire, mouse-adapted Zaire, and Reston Ebola viruses for interaction with all six members of the human karyopherin ␣ family. We found, in contrast to previous studies, that PY-STAT1 can interact not only with karyopherin ␣1 but also with karyopherins ␣5 and ␣6, which together comprise the NPI-1 subfamily of karyopherin ␣s. Similarly, all three VP24s bound and inhibited PY-STAT1 interaction with karyopherins ␣1, ␣5, and ␣6. Consistent with their ability to inhibit the karyopherin-PY-STAT1 interaction, Zaire, mouse-adapted Zaire, and Reston Ebola virus VP24s displayed similar capacities to inhibit IFN-␤-induced gene expression in human and mouse cells. These findings suggest that VP24 inhibits interaction of PY-STAT1 with karyopherins ␣1, ␣5, or ␣6 by binding within the PY-STAT1 binding region of the karyopherins and that this function is conserved among the VP24 proteins of different Ebola virus species.

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“…This is particularly important in view of recent findings showing that live viral infection with EBOV or MARV, as well as irradiated EBOV virus, does not cause maturation of human DCs (39,48). Monocytes, macrophages, and DCs appear to be the early targets of filovirus infections (39,49,50). Impaired DC maturation may, in part, explain the failure of infected individuals to mount a protective immune response to EBOV infection.…”

Section: Discussionmentioning

confidence: 99%

Ebola virus-like particles protect from lethal Ebola virus infection

Warfield

Bosio

Welcher

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

228

258

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The filovirus Ebola causes hemorrhagic fever with 70 -80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (

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Pathogenesis of Experimental Ebola Zaire Virus Infection in BALB/c Mice

Cited by 137 publications

References 18 publications

3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice

3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice

Ebola Virus VP24 Proteins Inhibit the Interaction of NPI-1 Subfamily Karyopherin α Proteins with Activated STAT1

Ebola virus-like particles protect from lethal Ebola virus infection

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