Biology Reference
In-Depth Information
recently, cathepsin L has been implicated in regulatory events relating to cancer,
diabetes, immunological responses, degradation of the articular cartilage matrix,
and other pathological processes (Vasiljeva
., 2007), including osteoporosis,
rheumatoid arthritis, and tumor metastasis (Palermo and Joyce, 2008).
Interestingly, several host cell proteases appear to be able to prime fusion
activation in the case of SARS-CoV, including cathepsin L, trypsin, factor Xa,
thermolysin, plasmin, TMPRSS11a, and elastase. The proteolytic cleavage events
in SARS-CoV S that lead to membrane fusion occur both at the S1/S2 boundary
and adjacent to a fusion peptide in the S2 domain (Belouzard
et al
., 2009). Elastase-
mediated activation of SARS-CoV was originally reported by Taguchi and cow-
orkers, and it has been proposed that elastase may have important implications for
viral pathogenesis (Matsuyama
et al
., 2005). Elastase is known to be secreted by
neutrophils as part of an inflammatory response to a viral infection and is also
produced by opportunistic bacteria (e.g.,
et al
) that can colonize
virally infected respiratory tissue. As such, it has been considered that elastase-
mediated activation of SARS-CoV might be an important factor in the severe
pneumonia seen in SARS-CoV-infected patients (Belouzard
Pseudomonas aeruginosa
., 2010).
In conclusion, in order to better classify the receptors, the receptors
must be differentiated according to their precise function: those that permit a
nonspecific adsorption, such as the glycosaminoglycans (used by Dengue, TBE,
HSV-1), the type C lectin receptors, such as L-SIGN, DC-SIGN, the hMGL, the
LSECtin, and the asialoglycoprotein receptor (used by HCV, Ebola, Marburg);
those that permit a specific adsorption receptor (binding receptor) allowing the
sorting (toward particular endosomes and intracytoplasmic compartment) and
the initial conformational changes (such as the CD4 to HIV, the integrins or the
laminin receptor for the Dengue, Sindbis, or Lassa viruses); and finally, those that
permit the exposition of the domains implicated in the destabilization of the
membrane (like the fusion peptide) and are the latest receptors to act (such as
the HIV coreceptors). Therefore, studying the kinetics of the conformation
changes of the EnvGP and the kinetics of action and utilization of the receptors
is essential to accurately categorize the receptors (nonspecific adsorption recep-
tor, receptor of binding, receptor of fusion).
All the cellular proteins that allow the exposition, localization, and the
trafficking of these receptors and/or endosomes should be considered as cofactors.
With all the siRNA screens that are coming out, the list of such cofactors is
dramatically increasing.
et al
B. Use of multiple receptors—Receptor switch
The use of different receptors often correlates with the need of a virus to
overcome barriers existing in the cell type or tissue that they infect. One well-
studied example is the binding of Coxsackievirus B to decay-accelerating factor
