Filoviridae

 http://www.ufrgs.br/imunovet/molecular_immunology/pathoviruses_filoviridae.html

• Ebolavirus (BSL4 agents; name arises from the river Ebola, in Sudan and Zaire)^ref
Epidemiology : since its discovery in 1976, there have been around 1,500 cases - more than 1,000 of which have been fatal. Antibody to Ebola virus was found in 14 (1.2%) of 1147 human sera collected in Gabon in 1981-1997. 6 seropositive subjects were bled in the northeast in 1991, .. .3 years prior to recognition of the 1st known outbreak of Ebola hemorrhagic fever (EHF), whilst 8 came from the southwest, where the disease has not been recognized. It has been reported elsewhere that 98 carcasses of wild animals were found in systematic studies in northeastern Gabon and adjoining northwestern Republic of the Congo (RoC) during 5 EHF epidemics in August 2001 to June 2003, with Ebola virus infection being confirmed in 14 carcasses. During the present opportunistic observations, reports were investigated of a further 397 carcasses, mainly gorillas, chimpanzees, mandrills and bush pigs, found by rural residents in 35 incidents in Gabon and RoC during 1994-2003. 16 incidents had temporal and/or spatial coincidence with confirmed EHF outbreaks, and the remaining 19 appeared to represent extension of disease from such sites. There appeared to be sustained Ebola virus activity in the northeast in 1994-1999, with sequential spread from 1996 onwards, 1st westwards, then southerly, and then northeastwards, reaching the Gabon-RoC border in 2001. This implies that there was transmission of infection between wild mammals, but the species involved are highly susceptible and unlikely to be natural hosts of the virus (Lahm SA, Kombila M, Swanepoel R, Barnes RF. Morbidity and mortality of wild animals in relation to outbreaks of Ebola hemorrhagic fever in Gabon, 1994-2003. Trans R Soc Trop Med Hyg. 2007 Jan;101(1):64-78)^ref
 
Genomics  : the Ebola virion is about 970 nm in length and the Ebola virus genome has several gene overlaps
Proteomics
• 4 virion structural proteins
• VP30
• VP35 blocks virus-induced interferon regulatory factor 3 (IRF-3) phosphorylation and subsequent IRF-3 dimerization and nuclear translocation, preventing the induction of antiviral genes, including IFN-b, ISG54 and ISG56
• nucleoprotein (NP)
• polymerase protein [L]
• 3 membrane-associated proteins : both VP40 and GP localize in lipid rafts
• matrix protein VP40 oligomerize at the plasma membrane
• glycoprotein [GP], whose gene is positioned fourth from the 3' end of the 7 linearly arranged genes. GP is encoded in 2 ORFs :
• ORF I (amino-terminal) encodes for a small (50-70 kD), soluble, nonstructural homodimeric secretory glycoprotein (sGP / SGP) that is secreted in large quantities early in Ebola infection : it binds to CD16b / FcgRIIIB on neutrophil and inhibits early activation (it also causes a profound lymphopenia, preventing an early and effective host immune response).
• ORF II encodes for a transmembrane glycoprotein (GP) of 120-150 kDa, which is incorporated into the Ebola virion as membrane-anchored trimer of heterodimers (peplomers or ‘spikes’ on the surface of virions). GP is cleaved at a single site in the N-terminal third of the molecule by furin, a cellular subtilisin/kexin-like convertase, into 2 peptides joined by a disulfide bond. Cathepsin B (CatB) and cathepsin L (CatL) mediate entry by carrying out proteolysis of the EboV glycoprotein subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs^ref.
• GP1 (N-terminal end)  is highly glycosylated and contains most of the N- and O-linked glycans present in the surface spike. GP1 projects away from the surface of the virion and probably functions in binding to currently unknown cell receptors on endothelial cells. Primate lentiviral binding C-type lectins CD209 / DC-SIGN and CD209L / L-SIGN act as cofactors for cellular entry by Ebola virus : DC-SIGN on the surface of dendritic cells is able to function as a trans receptor, binding Ebola virus particles and transmitting infection to susceptible cells. The glycosylation of GP1 affects the folding of the molecule and may also be important in immune evasion. Virions of Ebola viruses (and filoviruses in general) are resistant to neutralization by antibody specific for the surface glycoprotein, and this may be due to the large amount of nonimmunogenic carbohydrate covering GP1, accounting for 60% or more of the 130 kDa molecular weight
• GP2 contains an a-helical sequence important in trimerization through the formation of coiled coils. The GP2 trimer forms a membrane-anchored, rod-like stalk that stabilizes the peplomer and contains a sequence positioned near its N-terminus that has been shown in vitro to promote fusion of membranes (fusion peptide) dependent on the presence of phosphatidylinositol and calcium
The structural picture that is being revealed for the Ebola virus GP (as well as that of Marburg virus) is very similar to the glycoproteins of retroviruses and influenza viruses
The editing event that leads to GP expression is an insertion of a single extra adenosine at a run of seven adenosines in the middle of the coding region. This insertion connects the 0 and -1 frames that encode the full-length GP. SGP and GP share the same N-terminal 300 amino acids with unique C-termini, both in length and sequence

• VP24
13 distinct strains grouped into 4 distinct virus species :