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

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5 Results: Identification of a residue in hepatitis C virus E2
glycoprotein that determines scavenger receptor BI and CD81
receptor dependency and particle sensitivity to neutralising
antibodies.
In the previous chapter we established that SR-BI expression levels limit
HCVcc infection of Huh-7.5 cells (Figure 4-2), furthermore a cell culture
adapted strain of JFH-1 exhibited an altered dependence on SR-BI (Figure
4-7). To investigate this further we obtained a characterised JFH-1 cell culture
adapted virus from Jin Zhong and Frank Chisari of the Scripps Institute in La
Jolla. This mutant virus carries a single amino acid change of glycine to
arginine within the E2 glycoprotein; at position 451 of the polyprotein. Zhong
et. al. have previously reported that JFH-1 G451R has a higher specific
infectivity than JFH-1 wt and an altered relationship between particle density
and infectivity, suggesting changes in particle-lipoprotein interactions.
5.1 JFH-1 G451R has a reduced dependence on SR-BI.
To investigate whether the G451R mutation alters SR-BI dependence in a
manner similar to that seen in Figure 4-7, parental Huh-7.5 and cells
transduced to over express SR-BI were infected with JFH-1 wt and G451R.
We previously reported that HCV can infect hepatoma cells via cell-free and
cell-cell routes (314). To discriminate between cell-free particle primary
infection and secondary transmission events, infection was allowed to
proceed for 48 and 72 hrs, respectively (314). Over expression of SR-BI