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==Overview==
The Ebola virus infects the [[mononuclear]] phagocyte system, but also other [[cells]] such as [[hepatocytes]], [[spongiocytes]], [[fibroblasts]] and [[endothelial]] cells, inducing tissue [[necrosis]] and disrupting the [[hematological]] and [[coagulation]] systems. The Ebola virus is transmitted by direct contact with [[infected]] patients or animals. The [[natural reservoir]] has not been identified.<ref name="pmid8678836">{{cite journal| author=Ryabchikova E, Kolesnikova L, Smolina M, Tkachev V, Pereboeva L, Baranova S et al.| title=Ebola virus infection in guinea pigs: presumable role of granulomatous inflammation in pathogenesis. | journal=Arch Virol | year= 1996 | volume= 141 | issue= 5 | pages= 909-21 | pmid=8678836 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8678836  }} </ref><ref name="pmid9728532">{{cite journal| author=Bray M, Davis K, Geisbert T, Schmaljohn C, Huggins J| title=A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever. | journal=J Infect Dis | year= 1998 | volume= 178 | issue= 3 | pages= 651-61 | pmid=9728532 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9728532  }} </ref><ref name="pmid9988186">{{cite journal| author=Connolly BM, Steele KE, Davis KJ, Geisbert TW, Kell WM, Jaax NK et al.| title=Pathogenesis of experimental Ebola virus infection in guinea pigs. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S203-17 | pmid=9988186 | doi=10.1086/514305 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988186  }} </ref><ref name="pmid11798241">{{cite journal| author=Bray M, Hatfill S, Hensley L, Huggins JW| title=Haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of Ebola Zaire virus. | journal=J Comp Pathol | year= 2001 | volume= 125 | issue= 4 | pages= 243-53 | pmid=11798241 | doi=10.1053/jcpa.2001.0503 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11798241  }} </ref>


==Overview==
==Pathophysiology==
===Tropism===
* Ebola [[virus]] infects mainly the cells of the mononuclear phagocyte system, but also [[fibroblasts]], [[hepatocytes]], spongiocytes, adrenal cortical cells and [[endothelial cells]].<ref name="pmid8678836">{{cite journal| author=Ryabchikova E, Kolesnikova L, Smolina M, Tkachev V, Pereboeva L, Baranova S et al.| title=Ebola virus infection in guinea pigs: presumable role of granulomatous inflammation in pathogenesis. | journal=Arch Virol | year= 1996 | volume= 141 | issue= 5 | pages= 909-21 | pmid=8678836 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8678836  }} </ref>
* The [[infection]] of the mononuclear phagocyte system cells plays a key role in the pathogenesis and spread of the disease as they carry the virus from  of the initial [[infection]] site, through the [[lymphatic system]] and [[blood]], to the regional [[lymph nodes]],[[spleen]] and [[liver]].<ref name="pmid14633608">{{cite journal| author=Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB et al.| title=Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. | journal=Am J Pathol | year= 2003 | volume= 163 | issue= 6 | pages= 2347-70 | pmid=14633608 | doi=10.1016/S0002-9440(10)63591-2 | pmc=PMC1892369 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14633608  }} </ref>
* The next table summarizes the [[pathogenesis]] of the [[disease]] according to the [[virus]] [[tropism]].
{| style="border: 2px solid #DCDCDC; font-size: 90%; width: 60%;" align=center
|+ '''Pathogenesis'''
|-
! style="width: 80px; background: #4479BA; text-align: center;"|{{fontcolor|#FFF|Organ/Tissue}}
! style="width: 720px; background: #4479BA; text-align: center;"| {{fontcolor|#FFF|Effect}}
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''[[Endothelial cells]]'''
| style="background: #DCDCDC; padding: 5px;"| [[Glycoprotein|Glycoprotein (GP)]] on the [[virion]] [[viral envelope|envelope]] allows introduction of its content into the [[endothelial cell]]s, which induces a [[cytopathic effect]] and damage to the [[endothelial|endothelial]] barrier function that, together with effects of [[TNF-alpha|TNF-α]] released by infected [[mononuclear cell]]s, leads to the loss of vascular integrity and increased leakage.
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''[[Liver]]'''
| style="background: #DCDCDC; padding: 5px;"| Causes hepatocellular [[necrosis]] which could impair the synthesis of [[proteins]] of the [[coagulation system]]<ref name="pmid14633608">{{cite journal| author=Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB et al.| title=Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. | journal=Am J Pathol | year= 2003 | volume= 163 | issue= 6 | pages= 2347-70 | pmid=14633608 | doi=10.1016/S0002-9440(10)63591-2 | pmc=PMC1892369 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14633608  }} </ref>
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''[[Adrenal cortex]]'''
| style="background: #DCDCDC; padding: 5px;"| Affects the synthesis of enzymes responsible for the synthesis of [[steroids]], leading to [[hypotension]], and [[fluid]] and [[electrolytes]] disturbances.<ref name="pmid14633608">{{cite journal| author=Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB et al.| title=Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. | journal=Am J Pathol | year= 2003 | volume= 163 | issue= 6 | pages= 2347-70 | pmid=14633608 | doi=10.1016/S0002-9440(10)63591-2 | pmc=PMC1892369 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14633608  }} </ref>
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''[[Lymphatic system]]'''
| style="background: #DCDCDC; padding: 5px;"| [[Necrosis]] of the [[spleen]], [[lymph nodes]] and [[thymus]]; [[Apoptosis]] of [[lymphocytes]] leading to [[lymphopenia]].<ref name="pmid14633608">{{cite journal| author=Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB et al.| title=Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. | journal=Am J Pathol | year= 2003 | volume= 163 | issue= 6 | pages= 2347-70 | pmid=14633608 | doi=10.1016/S0002-9440(10)63591-2 | pmc=PMC1892369 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14633608  }} </ref><ref name="pmid9893381">{{cite journal| author=Zaki SR, Goldsmith CS| title=Pathologic features of filovirus infections in humans. | journal=Curr Top Microbiol Immunol | year= 1999 | volume= 235 | issue=  | pages= 97-116 | pmid=9893381 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9893381  }} </ref>
|}
<br>
 
===Immune response===
* The virus activates the [[macrophages]] synthesis of [[interleukins]] (IL), which leads the [[Th1]]/[[Th2]] balance towards a more pronounced [[Th1]]-[[cell]] mediated response.<ref name="pmid24284388">{{cite journal| author=Qiu X, Audet J, Wong G, Fernando L, Bello A, Pillet S et al.| title=Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb. | journal=Sci Rep | year= 2013 | volume= 3 | issue=  | pages= 3365 | pmid=24284388 | doi=10.1038/srep03365 | pmc=PMC3842534 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24284388  }} </ref>
* Some inflammatory mediators produced during the [[ebola virus]] infection include: [[interferon]] (IFN)-alpha, [[IFN]]-beta, [[IL-2]], [[IL-6]], [[IL-8]], [[IL-10]], [[interferon]]-inducible protein 10; monocyte chemoattractant protein 1; regulated upon activation normal T cell expressed and secreted ([[RANTES]]); [[TNF-alpha]]; and [[reactive oxygen]] and [[nitrogen species]].<ref name="pmid9988183">{{cite journal| author=Villinger F, Rollin PE, Brar SS, Chikkala NF, Winter J, Sundstrom JB et al.| title=Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S188-91 | pmid=9988183 | doi=10.1086/514283 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988183  }} </ref><ref name="pmid11803049">{{cite journal| author=Hensley LE, Young HA, Jahrling PB, Geisbert TW| title=Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily. | journal=Immunol Lett | year= 2002 | volume= 80 | issue= 3 | pages= 169-79 | pmid=11803049 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11803049  }} </ref><ref name="pmid11982604">{{cite journal| author=Baize S, Leroy EM, Georges AJ, Georges-Courbot MC, Capron M, Bedjabaga I et al.| title=Inflammatory responses in Ebola virus-infected patients. | journal=Clin Exp Immunol | year= 2002 | volume= 128 | issue= 1 | pages= 163-8 | pmid=11982604 | doi= | pmc=PMC1906357 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11982604  }} </ref>
* Some viral proteins, such as [[VP35]] and [[VP24]], block the type I [[interferon]] response, which plays a key role of the [[pathogenesis]] of the [[disease]].<ref name="pmid12829834">{{cite journal| author=Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Mühlberger E, Bray M et al.| title=The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. | journal=J Virol | year= 2003 | volume= 77 | issue= 14 | pages= 7945-56 | pmid=12829834 | doi= | pmc=PMC161945 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12829834  }} </ref>
* The [[reactive oxygen]] and [[nitrogen species]] contribute to the [[cell]] and [[tissue]] damage, and therefore [[vascular]] and [[organ]] damage.<ref name="pmid15367603">{{cite journal| author=Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ, Wagoner KD et al.| title=Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. | journal=J Virol | year= 2004 | volume= 78 | issue= 19 | pages= 10370-7 | pmid=15367603 | doi=10.1128/JVI.78.19.10370-10377.2004 | pmc=PMC516433 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15367603  }} </ref>
* The [[nitric oxide]] is known to be an important [[vasodilator]], therefore it plays and important role in the development of hypotension and shock.
 
===Coagulation system===
* Ebola infection is associated with hemorrhage in 50% of patients.
* Alterations of the [[coagulation]] system are induced by the [[ebola virus]], and are thought to be mediated by the production of [[tissue factor]]:<ref name="pmid14639531">{{cite journal| author=Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE| title=Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. | journal=J Infect Dis | year= 2003 | volume= 188 | issue= 11 | pages= 1618-29 | pmid=14639531 | doi=10.1086/379724 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14639531  }} </ref>
:*Consumption of [[clotting factors]]
:*Increased concentrations of [[fibrin]] degradation products
:*[[Disseminated intravascular coagulopathy]]
===Understanding the immune response to the disease===
In one case study performed on an individual who had severe [[Ebola|Ebola virus infection]] in Sierra Leone to further understand the [[immune response]] during all the stages of the disease.<ref name="urlLongitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease | Science Translational Medicine">{{cite web |url=http://stm.sciencemag.org/content/9/385/eaai9321 |title=Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease &#124; Science Translational Medicine |format= |work= |accessdate=}}</ref>
The individual was provided with supportive care only without any other experimental therapies.
Daily global [[gene expression]] in peripheral [[white blood cells]] was recorded and correlated with many clinical and laboratory aspects during the course of disease ([[Viral load]], [[Multiple organ ACdysfunction syndrome|multiple organ dysfunction]], [[Coagulopathy|coagulopathy,]] etc) till complete recovery after 33 days.


== Structure ==
The study enabled us to identify the host responses (the genomic shift between increased [[Gene expression|expression of genes]] involved in [[inflammation]] and [[Cell death|cell destruction]] to increased [[Gene expression|expression of genes]] promoting cell repair) that correlate with the viral clearance and recovery.
[[Image:ebola virus em.png|thumb|135px|[[electron microscope|Electron micrograph]] of the filamentous structure of Ebola]]
===Size and shape===
[[Electron microscope|Electron micrographs]] of members of ''Ebola virus'' show them to have the characteristic thread-like structure of a [[Filoviridae|filovirus]].<ref name="Klenk2004">{{cite book |title=Ebola and Marburg Viruses, Molecular and Cellular Biology |last=Klenk |first=Hans-Dieter |authorlink= |coauthors=Feldmann, Heinz |year=2004 |publisher=Horizon Bioscience |location=Wymondham, Norfolk |isbn=0954523237 |pages= }}</ref> EBOV VP30 is around 288 amino acids long.<ref name="Klenk2004" />  The virions are tubular and variable in shape and may appear as a "U", "6", coiled, circular, or branched shape, however, laboratory purification techniques, such as [[centrifugation]], may contribute to the various shapes.<ref name="Klenk2004" /> Virions are generally 80 [[nanometer|nm]] in diameter.<ref name="Klenk2004" /> They are variable in length, and can be up to 1400 nm long. On average, however, the length of a typical [[virion|Ebola virus]] is closer to 1000 nm. In the center of the virion is a structure called nucleocapsid,  which is formed by the helically wound viral genomic RNA complexed with the proteins ''NP, VP35, VP30'' and ''L''. It has a diameter of 40 &ndash; 50 nm and contains a central channel of 20–30 nm in diameter. Virally encoded [[glycoprotein]] (GP) spikes 10 nm long and 10 nm apart are present on the outer [[viral envelope]] of the virion, which is derived from the host cell membrane. Between envelope and nucleocapsid, in the so-called matrix space, the viral proteins VP40 and VP24 are located.


===Genome===
The study revealed that many changes in [[gene expression]] precede the change in the clinical status of the patient emphasizing the role of viral clearance in the cure of systemic illness.
Each virion contains one minor molecule of linear, single-stranded, [[Sense (molecular biology)|negative-sense]] RNA, totaling 18959 to 18961 nucleotides in length. The 3′ terminus is not polyadenylated and the 5′ end is not capped. It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end were sufficient for replication.<ref name="Klenk2004" /> It codes for seven structural proteins and one non-structural protein. The gene order is 3′ - leader - NP - VP35 - VP40 - GP/sGP - VP30 - VP24 - L - trailer - 5′; with the leader and trailer being non-transcribed regions which carry important signals to control transcription, replication and packaging of the viral genomes into new virions. The genomic material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA polymerase, are necessary to transcribe the viral genome into mRNAs, as well as for replication of the viral genome.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Mononegavirales]]
[[Category:Viral diseases]]
[[Category:Biological weapons]]
[[Category:Zoonoses]]
[[Category:Hemorrhagic fevers]]
[[Category:Needs overview]]
[[Category:Disease]]
{{WH}}
{{WS}}

Latest revision as of 17:38, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Michael Maddaleni, B.S.; Guillermo Rodriguez Nava, M.D. [2]

Overview

The Ebola virus infects the mononuclear phagocyte system, but also other cells such as hepatocytes, spongiocytes, fibroblasts and endothelial cells, inducing tissue necrosis and disrupting the hematological and coagulation systems. The Ebola virus is transmitted by direct contact with infected patients or animals. The natural reservoir has not been identified.[1][2][3][4]

Pathophysiology

Tropism

Pathogenesis
Organ/Tissue Effect
Endothelial cells Glycoprotein (GP) on the virion envelope allows introduction of its content into the endothelial cells, which induces a cytopathic effect and damage to the endothelial barrier function that, together with effects of TNF-α released by infected mononuclear cells, leads to the loss of vascular integrity and increased leakage.
Liver Causes hepatocellular necrosis which could impair the synthesis of proteins of the coagulation system[5]
Adrenal cortex Affects the synthesis of enzymes responsible for the synthesis of steroids, leading to hypotension, and fluid and electrolytes disturbances.[5]
Lymphatic system Necrosis of the spleen, lymph nodes and thymus; Apoptosis of lymphocytes leading to lymphopenia.[5][6]


Immune response

Coagulation system

  • Ebola infection is associated with hemorrhage in 50% of patients.
  • Alterations of the coagulation system are induced by the ebola virus, and are thought to be mediated by the production of tissue factor:[13]

Understanding the immune response to the disease

In one case study performed on an individual who had severe Ebola virus infection in Sierra Leone to further understand the immune response during all the stages of the disease.[14] The individual was provided with supportive care only without any other experimental therapies. Daily global gene expression in peripheral white blood cells was recorded and correlated with many clinical and laboratory aspects during the course of disease (Viral load, multiple organ dysfunction, coagulopathy, etc) till complete recovery after 33 days.

The study enabled us to identify the host responses (the genomic shift between increased expression of genes involved in inflammation and cell destruction to increased expression of genes promoting cell repair) that correlate with the viral clearance and recovery.

The study revealed that many changes in gene expression precede the change in the clinical status of the patient emphasizing the role of viral clearance in the cure of systemic illness.

References

  1. ↑ 1.0 1.1 Ryabchikova E, Kolesnikova L, Smolina M, Tkachev V, Pereboeva L, Baranova S; et al. (1996). "Ebola virus infection in guinea pigs: presumable role of granulomatous inflammation in pathogenesis". Arch Virol. 141 (5): 909–21. PMID 8678836.
  2. ↑ Bray M, Davis K, Geisbert T, Schmaljohn C, Huggins J (1998). "A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever". J Infect Dis. 178 (3): 651–61. PMID 9728532.
  3. ↑ Connolly BM, Steele KE, Davis KJ, Geisbert TW, Kell WM, Jaax NK; et al. (1999). "Pathogenesis of experimental Ebola virus infection in guinea pigs". J Infect Dis. 179 Suppl 1: S203–17. doi:10.1086/514305. PMID 9988186.
  4. ↑ Bray M, Hatfill S, Hensley L, Huggins JW (2001). "Haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of Ebola Zaire virus". J Comp Pathol. 125 (4): 243–53. doi:10.1053/jcpa.2001.0503. PMID 11798241.
  5. ↑ 5.0 5.1 5.2 5.3 Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB; et al. (2003). "Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection". Am J Pathol. 163 (6): 2347–70. doi:10.1016/S0002-9440(10)63591-2. PMC 1892369. PMID 14633608.
  6. ↑ Zaki SR, Goldsmith CS (1999). "Pathologic features of filovirus infections in humans". Curr Top Microbiol Immunol. 235: 97–116. PMID 9893381.
  7. ↑ Qiu X, Audet J, Wong G, Fernando L, Bello A, Pillet S; et al. (2013). "Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb". Sci Rep. 3: 3365. doi:10.1038/srep03365. PMC 3842534. PMID 24284388.
  8. ↑ Villinger F, Rollin PE, Brar SS, Chikkala NF, Winter J, Sundstrom JB; et al. (1999). "Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection". J Infect Dis. 179 Suppl 1: S188–91. doi:10.1086/514283. PMID 9988183.
  9. ↑ Hensley LE, Young HA, Jahrling PB, Geisbert TW (2002). "Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily". Immunol Lett. 80 (3): 169–79. PMID 11803049.
  10. ↑ Baize S, Leroy EM, Georges AJ, Georges-Courbot MC, Capron M, Bedjabaga I; et al. (2002). "Inflammatory responses in Ebola virus-infected patients". Clin Exp Immunol. 128 (1): 163–8. PMC 1906357. PMID 11982604.
  11. ↑ Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Mühlberger E, Bray M; et al. (2003). "The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3". J Virol. 77 (14): 7945–56. PMC 161945. PMID 12829834.
  12. ↑ Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ, Wagoner KD; et al. (2004). "Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels". J Virol. 78 (19): 10370–7. doi:10.1128/JVI.78.19.10370-10377.2004. PMC 516433. PMID 15367603.
  13. ↑ Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE (2003). "Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event". J Infect Dis. 188 (11): 1618–29. doi:10.1086/379724. PMID 14639531.
  14. ↑ "Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease | Science Translational Medicine".

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