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Hello. My name is
Professor John Dillon
of University of Dundee.
I'm a professor of hepatology,
and I'm going to talk today
about HCV resistance.
0:11
HCV is a virus.
It's an enveloped virus.
It's a single-stranded,
positive-sense RNA virus.
It's a part of the
Flaviviridae genus,
or family rather,
and is its own genus.
The genome length of
approximately 9.6 kilobases.
0:32
There are seven HCV genotypes,
although a probable eighth
genotype has been described,
and within each of
those genotypes
there are multiple subtypes.
There are six main
genotypes worldwide.
Genotype 7 and genotype
8 don't have much
therapeutic implications.
Each genotype has a reference
nucleotide sequence
and, therefore, an
amino acid sequence,
and a substitution.
A difference in amino acid at
a defined position
of the HCV protein
between a patient's HCV and
the reference HCV protein
is termed a substitution.
You'd also think of
it as a polymorphism,
in more generic terms,
and that's the terminology that's
still preferred by the FDA.
Most experts will use
the word "substitution,"
and in the resistance context,
we will refer to them as
resistance-associated
substitutions.
Some older literature will
also refer to them as
resistant-associated variants,
but that term is now
not the preferred term.
1:35
On this slide, there
is an illustration
of the relationships between
the different genotypes
and subtypes within
the genotypes,
showing how much variation
there is in genetic sequence.
This analysis is done as
a phylogenetic analysis
to illustrate the variation
between the viruses,
so it's an important takeaway
message from this slide,
that there is huge variation
in the hepatitis C virus.
