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fredag 4 mars 2011

Afrikan Ebolavirus aiheuttaa verenvuotokuumetta. Filippiinien Reston Ebolavirus ei.

  • LÄHDE 1.
Dr Heinz Feldmann MD a b, Thomas W Geisbert PhD cEbola haemorrhagic fever
The Lancet, Volume 377, Issue 9768, Pages 849 - 862, 5 March 2011
doi:10.1016/S0140-6736(10)60667-8Cite or Link Using DOI
Published Online: 16 November 2010

Summary

Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines.

Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism.

Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available.Ebola virus infections are characterised by

  • immune suppression and
  • a systemic inflammatory response that causes
  • impairment of the vascular, coagulation, and immune systems,
  • leading to multiorgan failure and shock,
  • and thus, in some ways, resembling septic shock.
Lancet

  • LÄHDE 2. 

Siddhartha Mahanty a, Dr Mike Bray b
Pathogenesis of filoviral haemorrhagic fevers
The Lancet Infectious Diseases, Volume 4, Issue 8, Pages 487 - 498, August 2004
doi:10.1016/S1473-3099(04)01103-XCite or Link Using DOI

Summary

The filoviruses, marburgvirus and ebolavirus, cause epidemics of haemorrhagic fever with high casefatality rates.

The severe illness results from a complex of pathogenetic mechanisms that enable the virus
  • to suppress innate and adaptive immune responses,
  • infect and kill a broad variety of cell types,
  • and elicit strong inflammatory responses
  • and disseminated intravascular coagulation (DIC),
  • producing a syndrome resembling septic shock.
Most experimental data have been obtained on Zaire ebolavirus, which causes uniformly lethal disease in experimentally infected non-human primates but produces a broader range of outcomes in naturally infected human beings.
10—30% of patients can survive the illness by mobilising adaptive immune responses, and there is limited evidence that mild or symptomless infections also occur.

The other filoviruses that have caused human disease, Sudan ebolavirus, Ivory Coast ebolavirus, and marburgvirus, produce a similar illness but with somewhat lower case-fatality rates.

Variations in outcome during an epidemic might be due partly to genetically determined differences in innate immune responses to the viruses.
  • Recent studies in non-human primates have shown that blocking of certain host responses, such as the coagulation cascade, can result in reduced viral replication and improved host survival.

onsdag 9 februari 2011

Ebolas Tansaniassa. Uusi kanta?Ebolan reservoaariisäntää etsitään.

Eilen luin uutisissa maininnan mahdollisesta uudesta ebolakannasta, joka on ilmeentynyt juuri Tansaniassa , mutta enempää ei eilinen uutinen selvittänyt.

Mutta missä Ebola väliaikoina piileskelee? Tätä tutkitaan intensiivisesti ja on päädytty erääseen lepakkolajiin ainakin yhtenä ehdokkaana (Fruit Bats)
Seuraavaa faktaa on luonnon reservoaarista:

Natural reservoir

* The natural reservoir of the Ebola virus is unknown despite extensive studies, but it seems to reside in the rain forests on the African continent and in the Western Pacific.

EBOLA-viruksen luonnonreservoaari on tuntematon laajoista tutkimuksista huolimatta, mutta tiedetään sen oleskelevan Afrikan mantereeen sademetsissä ja Läntisen Tyynen meren seuduilla.

* Although non-human primates have been a source of infection for humans, they are not thought to be the reservoir. They, like humans, are believed to be infected directly from the natural reservoir or through a chain of transmission from the natural reservoir.

Vaikka ihmisille tulee tartuntaa kädellisistä eläimistä, niitä ei kuitenkaan pidetä taudin reservoaarina. Nekin infektoituvat jostain luonnonlähteestä käsin tai jostain tartuntaketjusta käsin.

* On the African continent, Ebola infections of human cases have been linked to direct contact with gorillas, chimpanzees, monkeys, forest antelope and porcupines found dead in the rainforest. So far, the Ebola virus has been detected in the wild in carcasses of chimpanzees (in Côte-d’Ivoire and the Republic of the Congo), gorillas (Gabon and the Republic of the Congo) and duikers (the Republic of the Congo).

Afrikassa ihmiset ovat saaneet ebolatartuntaa suorasta kontaktista gorilloihin, simpansseihin, apinoihin, puikkija-antilooppeihin ja piikkisikoihin, joita löytyy kuolleina sademetsistä.

* Different hypotheses have been developed to explain the origin of Ebola outbreaks. Laboratory observation has shown that bats experimentally infected with Ebola do not die, and this has raised speculation that these mammals may play a role in maintaining the virus in the tropical forest.

On tehty oletus toisensa jälkeen ebolapurkausten selityksiksi. Laboratoriotutkimukset ovat osoittaneet, että kokeellisesti ebolalla infektoidut lepakot eivät menehdy ja tästä on arveltu, että nämä nisäkäseläimet voisivat olla virusta ylläpitäviä troppisissa metsiköissä.

* Extensive ecological studies are under way in the Republic of the Congo and Gabon to identify the Ebola's natural reservoir. (WHO)

laajoja ekologisia tutkimuksia on meneillään Kongossa ja Gabonissa, jotat löydettäisiin Ebolan luonnolloset reservoaarit. (WHO lähteestä)

tisdag 1 februari 2011

YFV patofysiologiasta

Large vaccination campaigns and A aegypti control programs have decreased the incidence of yellow fever worldwide. Despite the availability of an effective live-attenuated 17D vaccine, yellow fever has reemerged across Africa and South America. The populations at highest risk for the illness are those in the poorest countries in the world that lack funding or infrastructure to support a widespread vaccination program. A aegypti mosquitoes are now present in the Americas, and there is a concern that large yellow fever outbreaks could occur.

Flaviviruses, including those that cause yellow fever, also have a potential use as a biologic weapon.3 For more information, see the article CBRNE - Viral Hemorrhagic Fevers in eMedicine’s Emergency Medicine volume.

Pathophysiology

Yellow fever virus is a positive-sense, single-stranded, RNA-enveloped flavivirus with a diameter of about 50-60 nm. The virus is transmitted via the saliva of an infected mosquito. Local replication of the virus takes place in the skin and regional lymph nodes. Viremia and dissemination follows.

The virus gains entrance through receptor-mediated endocytosis. RNA synthesis occurs in the cytoplasm and protein synthesis in the endoplasmic reticulum. Virions are released through the cell membrane. Its viral envelope contains a lipid bilayer taken from the infected cell. Virulence factors include the following:

  • Capsid protein C facilitates viral binding.
  • Membrane protein M is a minor glycoprotein.
  • E proteins initiate infection and mediate viral entry.
  • Nonstructural protein 1 (NS1) may play a role in RNA replication.
  • NS2A protein is involved in RNA replication and packaging.
  • NS2B and NS3 form a complex and are involved in polyprotein processing and replication of RNA.
  • NS5 has a major role in RNA replication.

The E protein interacts with the cellular receptor, and virions are endocytosed into the dendritic cells. Subsequently, epidermal dendritic cells and lymph channels disseminate virions. After invasion in the host, Kupffer cells (fixed liver macrophages) are infected within 24 hours.

The infection quickly disseminates to kidneys, lymph nodes, spleen, and bone marrow. Renal failure occurs as renal tubules undergo fatty change and eosinophilic degeneration, likely due to direct viral effect, hypotension, and hepatic involvement.

Liver involvement is a late manifestation of the infection. Direct viral effects lead to apoptotic cell death of the midzonal hepatic cells. Vitamin K–depleted clotting factors and disseminated intravascular coagulation lead to coagulopathy and bleeding. Hepatic involvement is associated with higher risk of mortality.

Finally, circulatory shock develops secondary to cytokine storm, with evidence of increased levels of interleukin (IL)–6, IL-1 receptor antagonist, inferno-inducible protein-10, and tumor necrosis factor (TNF)–alpha. Viral antigens are found diffusely in kidneys, myocardium, and hepatocytes. In individuals who survive yellow fever, the recovery is complete, with no residual fibrosis.

Keltakuumeviruksen elämänsykli

http://www.bio.davidson.edu/people/sosarafova/Assets/Bio307/mepeele/page01.html

The Yellow Fever Virus

  • Fagosytoituminen makrofagiin ihmiskehossa. Virus tekee makrofagin kyvyttömäski sulattamaan itseään.

Upon entering the host, the virus waits to be phagocytosed by a macrophage. Immediately following phagocytosis, the virus sheds its envelope and disables further digestion by the macrophage.

  • Ehjä virus makrofagissa saapuu imusolmukkeeseen ja siellä virus alkaa replikoitua.

The macrophage continues with the healthy virus to the lymph nodes where the virus begins replication in earnest.

  • Virus hajoittaa isäntäsolunsa makrofagin ja koettaa infektoida uusia makrofageja.

The virus lyses its host macrophage and seeks to infect other macrophages.

  • Imusolmukkeesta virus päässee veren kierron mukana maksaan.

From the lymph node the virus is eventually carried through the blood stream to the liver.

  • Maksassa YFV infektoi Kupfferin solulinjaa, joka reunustaa maksan verisuonia. Kupfferin solut ovat sellaisia makrofageja, jota maksan alueella ovat vastuussa solujätteen ja verenkierrosta tulevien vaurioituneitten verisolujen hävittämisestä.

Once in the liver, the virus is able to infect Kupffer cells lining bloodvessels in the liver. The Kupffer cells are macrophages residing in the liver responsible for clearing cellular debris and dead and damaged blood cells from the bloodstream.

  • Kupfferin solujen infektoituminen ja kuolema vaurioittaa ympäröivät maksasolut ja johtavat hyaliinin muodostumiseen, mikä on keltakuumeelle tunnusomaista.

The infection and death of Kupffer cells damages surrounding hepatocytes, leading to the formation of translucent hyaline "councilman bodies," the hallmark of yellow fever.

  • Maksan vaurio estää maksan tärkeää funktiota: sapen alkuaine bilirubiini ei voi muuntua biliverdiiniksi, mistä seuraa potilaan keltainen väri, "keltakuume"

Liver damage prevents the bile precursor bilirubin from being converted to biliverdin, leading to the most visible symptom of yellow fever; jaundice.

  • Kun virus on lisääntynyt hyvin runsaasti ja maksavaurio on laaja, oireita on lievästä flunssan tapaisesta nivelkipuihin, aivotulehdukseen ja verenvuototautiin asti.

Once the virus has heavily replicated and liver damage is extensive symptoms ranging from flu-like symptoms, joint-pain, encephalitis, and hemorrhagic disease develop.

  • Keltakuume johtaa menehtymiseen 10-30%:ssa tapauksista. kun tauti on systeeminen, hyttysen saamista veriaterioista virus aloittaa uuden elinkiertonsa.

Yellow fever is lethal in 10-30% of cases. Once systemic, the virus is collected from the bloodstream by mosquitos, where it begins its life cycle again.

Barnes E. Diseases and Human Evolution. Albuquerque : University of New Mexico Press, 2005.

Tesh RB, Guzman H, Travassos de Rosa APA, Bunnell JE, Zhang H, Xiao SY. 2001. Experimental Yellow Fever Virus in the Golden Hamster (Mesocricetus auratus). I. Virologic, Biochemical, and Immunologic Studies. The Journal of Infectious Diseases 183: 1435.

Keltakuumeviruksen genotyypeistä

Results: 1 to 20 of 66

1.

Yellow fever virus in Haemagogus leucocelaenus and Aedes serratus mosquitoes, southern Brazil, 2008.

Cardoso Jda C, de Almeida MA, dos Santos E, da Fonseca DF, Sallum MA, Noll CA, Monteiro HA, Cruz AC, Carvalho VL, Pinto EV, Castro FC, Nunes Neto JP, Segura MN, Vasconcelos PF.

Emerg Infect Dis. 2010 Dec;16(12):1918-24.PMID: 21122222 [PubMed - in process]Free ArticleRelated citations

2.

Molecular Epidemiology of Yellow Fever in Bolivia from 1999 to 2008.

Baronti CX, Goitia NJ, Cook S, Roca Y, Revollo J, Flores JV, de Lamballerie X.

Vector Borne Zoonotic Dis. 2010 Oct 6. [Epub ahead of print]PMID: 20925524 [PubMed - as supplied by publisher]Related citations

3.

Yellow fever virus maintenance in Trinidad and its dispersal throughout the Americas.

Auguste AJ, Lemey P, Pybus OG, Suchard MA, Salas RA, Adesiyun AA, Barrett AD, Tesh RB, Weaver SC, Carrington CV.

J Virol. 2010 Oct;84(19):9967-77. Epub 2010 Jul 14.PMID: 20631128 [PubMed - indexed for MEDLINE]Related citations

4.

Genetic relationships among populations of Aedes aegypti from Uruguay and northeastern Argentina inferred from ISSR-PCR data.

Soliani C, Rondan-Dueñas J, Chiappero MB, Martínez M, Da Rosa EG, Gardenal CN.

Med Vet Entomol. 2010 Sep;24(3):316-23. Epub 2010 Jul 4.PMID: 20626627 [PubMed - indexed for MEDLINE]Related citations

5.

Genome-based polymorphic microsatellite development and validation in the mosquito Aedes aegypti and application to population genetics in Haiti.

Lovin DD, Washington KO, deBruyn B, Hemme RR, Mori A, Epstein SR, Harker BW, Streit TG, Severson DW.

BMC Genomics. 2009 Dec 9;10:590.PMID: 20003193 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

6.

Two different routes of colonization of Aedes aegypti in Argentina from neighboring countries.

Dueñas JC, Llinás GA, Panzetia-Dutari GM, Gardenal CN.

J Med Entomol. 2009 Nov;46(6):1344-54.PMID: 19960679 [PubMed - indexed for MEDLINE]Related citations

7.

Detection of a new yellow fever virus lineage within the South American genotype I in Brazil.

de Souza RP, Foster PG, Sallum MA, Coimbra TL, Maeda AY, Silveira VR, Moreno ES, da Silva FG, Rocco IM, Ferreira IB, Suzuki A, Oshiro FM, Petrella SM, Pereira LE, Katz G, Tengan CH, Siciliano MM, Dos Santos CL.

J Med Virol. 2010 Jan;82(1):175-85.PMID: 19950229 [PubMed - indexed for MEDLINE]Related citations

8.

A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

Meier KC, Gardner CL, Khoretonenko MV, Klimstra WB, Ryman KD.

PLoS Pathog. 2009 Oct;5(10):e1000614. Epub 2009 Oct 9.PMID: 19816561 [PubMed - indexed for MEDLINE]Free PMC ArticleFree textRelated citations

9.

Reduced levels of genetic variation in Aedes albopictus (Diptera: Culicidae) from Manaus, Amazonas State, Brazil, based on analysis of the mitochondrial DNA ND5 gene.

Maia RT, Scarpassa VM, Maciel-Litaiff LH, Tadei WP.

Genet Mol Res. 2009 Aug 18;8(3):998-1007.PMID: 19731220 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

10.

Gene flow, subspecies composition, and dengue virus-2 susceptibility among Aedes aegypti collections in Senegal.

Sylla M, Bosio C, Urdaneta-Marquez L, Ndiaye M, Black WC 4th.

PLoS Negl Trop Dis. 2009;3(4):e408. Epub 2009 Apr 14.PMID: 19365540 [PubMed - indexed for MEDLINE]Free PMC ArticleFree textRelated citations


13.

The enigma of yellow fever in East Africa.

Ellis BR, Barrett AD.

Rev Med Virol. 2008 Sep-Oct;18(5):331-46. Review.PMID: 18615782 [PubMed - indexed for MEDLINE]Related citations

14.

The Yin and Yang of linkage disequilibrium: mapping of genes and nucleotides conferring insecticide resistance in insect disease vectors.

Black WC 4th, Gorrochetegui-Escalante N, Randle NP, Donnelly MJ.

Adv Exp Med Biol. 2008;627:71-83. Review.PMID: 18510015 [PubMed - indexed for MEDLINE]Related citations

15.

Mitochondrial DNA polymorphism and heteroplasmy in populations of Aedes aegypti in Brazil.

Paduan Kdos S, Ribolla PE.

J Med Entomol. 2008 Jan;45(1):59-67.PMID: 18283943 [PubMed - indexed for MEDLINE]Related citations

16.

A mutation in the voltage-gated sodium channel gene associated with pyrethroid resistance in Latin American Aedes aegypti.

Saavedra-Rodriguez K, Urdaneta-Marquez L, Rajatileka S, Moulton M, Flores AE, Fernandez-Salas I, Bisset J, Rodriguez M, McCall PJ, Donnelly MJ, Ranson H, Hemingway J, Black WC 4th.

Insect Mol Biol. 2007 Dec;16(6):785-98.PMID: 18093007 [PubMed - indexed for MEDLINE]Related citations

17.

Yellow fever: a disease that has yet to be conquered.

Barrett AD, Higgs S.

Annu Rev Entomol. 2007;52:209-29. Review.PMID: 16913829 [PubMed - indexed for MEDLINE]Related citations

18.

Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad.

Cha SJ, Chadee DD, Severson DW.

Am J Trop Med Hyg. 2006 Jul;75(1):70-7.PMID: 16837711 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

19.

Amplified fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the yellow fever mosquito Aedes aegypti.

Zhong D, Menge DM, Temu EA, Chen H, Yan G.

Genetics. 2006 Jul;173(3):1337-45. Epub 2006 Apr 19.PMID: 16624910 [PubMed - indexed for MEDLINE]Free PMC ArticleFree textRelated citations

20.

Genome analysis and phylogenetic relationships between east, central and west African isolates of Yellow fever virus.

von Lindern JJ, Aroner S, Barrett ND, Wicker JA, Davis CT, Barrett AD.

J Gen Virol. 2006 Apr;87(Pt 4):895-907.PMID: 16528039 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

lördag 29 januari 2011

Maksalektiini, ASGR1. Kiiniittyykö HBV virus maksasolussa tähän?

http://www.wikigenes.org/e/gene/e/432.html
Gene Review: asialoglycoprotein receptor 1 ( ihmisellä)

ASGR1

Synonyms: ASGP-R 1, ASGPR, ASGPR 1, Asialoglycoprotein receptor , C-type lectin domain family 4 member H1, ...
Yang, J.et al.
Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro.
Department of Infectious Diseases, The First Affiliated Hospital of Medical college of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an 710061, Shaanxi Province, China.

Abstract

BACKGROUND: The preS1 domain of the large envelope protein has been identified as an essential viral structure involved in hepatitis B virus (HBV) attachment. However, the cellular receptor(s) for HBV has not yet been identified.
AIMS: To identify a cell-surface receptor for HBV, which could elucidate the molecular mechanism of HBV infection.
METHODS: A novel yeast two-hybrid system was used to screen proteins interacting with the preS1 region of HBV. Their interaction was verified by yeast cotransformation, coimmunoprecipitation and mammalian two-hybrid assay, while their intracellular and tissue localization was analyzed by confocal microscopy and immunohistochemistry, respectively.
RESULTS: Asialoglycoprotein receptor (ASGPR) interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro. The levels of expression of preS1 and ASGPR in the liver were similar and correlated with each other.
CONCLUSIONS: ASGPR is a candidate receptor for HBV that mediates further steps of HBV entry.
PMID: 21207081 [PubMed - as supplied by publisher]
Suom.
ASGPR on kandidaattireseptori hepatiitti B virukselle ja toimii välittämällä viruksen etenemistä maksasolun sisäänmenoprosessissa (ENTRY).

HBV sitovasta proteiinista, HBV:n integroitunut ccc DNA,

Kerään tähän kohtaan lähteitä HBV viruksen maksasoluun menoa kuvaavista asioista.
http://abbs.oxfordjournals.org/content/38/7/484.abstract

J Viral Hepat. 2006 Jan;13(1):11-8 
Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry.

Abstract
The cellular receptor for hepatitis B virus (HBV) infection has not yet been identified. The purpose of this study was to address the possibility of participation by desialylated HBV and the asialoglycoprotein receptor (ASGP-R) exclusively expressed on liver parenchymal cells, in infection.

 Assays for viral binding and entry were performed by culturing a hepatoblastoma cell line, HepG2, and HBV particles derived from the HBV carrier in the presence or absence of neuraminidase (NA).

 Viral binding and entry were clearly enhanced in the presence of NA, and the enhancement of the binding could be blocked by asialo-fetuin and ethylenediamine-tetraacetic acid (EDTA).

 In addition, covalently closed circular (CCC)-DNA, as a marker of infectivity, was detected in the presence of NA, but not in its absence.

 The optimal concentration of NA raised infectivity more than 1000 times. We concluded that this method makes it feasible to evaluate the infectivity of HBV in vitro and that ASGP-R may be a specific HBV receptor once viral particles are desialylated.
21.4. 2014