Leta i den här bloggen

tisdag 21 oktober 2014

PAMP patogeenin tunnistusjärjestelmä ja Ebolavirus .RIG-1 ja MDA5. Miten evaasio? Rokotteesta.

Löysin saksalaisen katsauksn jossa mainittiin myös ebolasta.
 Im Gegensatz zu MDA5 entdeckt RIG-I relativ kurze dsRNA (bis zu 1000 bp).

Intracellular Viral RNA Sensors: RIG‑I Like Receptors

Engl.  http://en.wikipedia.org/wiki/Pattern_recognition_receptor

Filovirustropismi. Soluun sisäänmenossa viruksen käyttämät  molekyylit
Rokotuksen periaate

Hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, all of which express C-type lectins, are thought to be the preferred target cells of filoviruses (Takada and Kawaoka, 2001; Geisbert and Hensley, 2004; Hoenen et al., 2006). Indeed, primary macrophage and dendritic cell cultures transduced for C-type lectin expression greatly increased their susceptibility to virus infection (Simmons et al., 2003a; Marzi et al., 2007). While C-type lectins do not directly mediate filovirus entry, their pattern of expression in vivo and their ability to enhance infection indicate that C-type lectins can play an important role in filovirus transmission and tissue tropism. Thus, increased infection of these cells might be directly involved in the pathogenesis of filoviruses.

 Accordingly, it was shown that soluble mannose-binding C-type lectin played a role in protection from lethal Ebola virus infection in a mouse model (Michelow et al., 2011). It should be noted that the ability to utilize the C-type lectins (i.e., DC-SIGN and hMGL) to promote cellular entry was correlated with the different pathogenicities among filoviruses (Takada et al., 2004; Marzi et al., 2006; Matsuno et al., 2010a). Interestingly, the MLR (mucin like region)  amino acid sequence does not seem to be the primary factor contributing to the difference (Marzi et al., 2006; Matsuno et al., 2010a; Usami et al., 2011). Although there might be some distinct mechanisms of entry between MARV and EBOV (Chan et al., 2000), the similarity of tissue tropism and pathological features of infection between these viruses suggests that C-type lectins are one of the important molecules, likely as attachment factors, for filovirus entry into cells, and that they are directly involved in filovirus tropism at the cellular level.
Recently, GP has been used for viral vector-based or DNA vaccines that were shown to protect animals effectively. Replication-incompetent adenovirus expressing GP, a replication-competent vesicular stomatitis virus expressing GP, and a recombinant paramyxovirus expressing GP have been shown to protect non-human primates from lethal infections of filoviruses (Sullivan et al., 2000, 2003; Jones et al., 2005; Bukreyev et al., 2007; Feldmann et al., 2007).

 It should be noted that these vaccines potentially induce cytotoxic cellular response (i.e., CD8+ T lymphocytes) as well as antibody production, suggesting that activating cytotoxic T-cells is a key protective mechanism (Olinger et al., 2005; Sullivan et al., 2006; Reed and Mohamadzadeh, 2007).

 Since cytotoxic T-cell response cannot be fully induced by immunization with non-replicative protein antigens such as inactivated virus and subunit vaccines, viral vector-based, or DNA vaccines may be promising in preventing filovirus infection.

Inga kommentarer:

Skicka en kommentar