The role of scavenger receptor BI in hepatitis - eTheses Repository ...

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inhibition of protein kinase A (PKA) activity in target cells reduces HCVcc and
HCVpp infection, correlating with a re-localisation of CLDN1 into intracellular
vesicles (94). Brazzoli et. al. used siRNA silencing of Rho family GTPases to
abrogate HCV infection, they attributed this phenotype to the ability of HCV E2
to induce Rho dependent re-localisation of CD81, suggesting that HCV may
be able to orchestrate molecular events necessary for viral entry (47).
Hepatocytes, as discussed earlier, are a polarised cell type and reside in a
highly ordered three dimensional structure, it is unknown what implications
this has for HCV infection. Whether the cultured hepatoma cells used for in
vitro HCV infection are capable of polarisation remains a controversial topic
(204, 342). In this respect they may represent a poor mimic of the hepatic
environment and work has begun to address HCV receptor expression in
polarised systems.
The most comprehensive study thus far involved the infection of Caco-2
(colorectal adenocarcinoma) cells by HCVcc/pp (204). Although these cells
express the 3 major HCV co-receptors they are minimally permissive to
infection. However, this is balanced by the fact that Caco-2 cells are a widely
recognised model of a polarised cell and provide a stepping stone to
understanding HCV interactions with hepatocytes. The expression levels and
localisation of the HCV receptors altered greatly depending on the degree of
Caco-2 polarisation. HCVpp entry occurred preferentially via the apical
surface and disruption of tight junctions enhanced infection, suggesting
laterally located co-receptors are inaccessible to the virus in Caco-2 cells