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

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1.2 An elusive pathogen.<br />

9<br />

<strong>The</strong> emergence <strong>of</strong> a new human pathogen presents the greatest <strong>of</strong><br />

challenges to modern virology and the discovery <strong>of</strong> human immunodeficiency<br />

virus (HIV) <strong>in</strong> the early 1980s set a precedent for the field. <strong>The</strong> discipl<strong>in</strong>e <strong>of</strong><br />

virology was not quite 100 years old when HIV was first isolated (15).<br />

However, pr<strong>of</strong>icient replication <strong>of</strong> HIV <strong>in</strong> vitro allowed the scientific community<br />

to characterise the virus exceptionally quickly. From the identification <strong>of</strong> HIV,<br />

to approval <strong>of</strong> the first specific therapy (AZT) by the Food and Drug<br />

Adm<strong>in</strong>istration took less than 5 years (213, 226) (and FDA website).<br />

Developments came so quickly that CD4 was identified as the major entry<br />

<strong>receptor</strong> before the politics <strong>of</strong> nam<strong>in</strong>g the new pathogen had been resolved<br />

(178, 199, 272).<br />

As illustrated by HIV, rapid progress <strong>in</strong> the study <strong>of</strong> a virus requires an<br />

appropriate model system capable <strong>of</strong> support<strong>in</strong>g virus replication; from its<br />

<strong>in</strong>ception virology has been dom<strong>in</strong>ated by species for which such platforms<br />

exist. Early research focused on viruses that <strong>in</strong>fect hosts such as bacteria,<br />

plants and birds. Dur<strong>in</strong>g the mid 20 th century, the advent <strong>of</strong> mammalian cell<br />

culture allowed fast and consistent <strong>in</strong> vitro studies <strong>of</strong> viral replication.<br />

However, not all viruses replicate <strong>in</strong> vitro, which presents a problem when<br />

study<strong>in</strong>g pathogens with host ranges limited to humans and higher primates<br />

(78).<br />

In vivo, it is thought that HCV replicates <strong>in</strong> hepatocytes with<strong>in</strong> the liver.<br />

However, the hepatocyte is a highly specialised cell type and the liver a

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