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Diversity of HCV in Relation to Times of Transmission
The rate of sequence change of HCV in vivo was used to date the
spread of HCV genotype 1b in European, USA and Japanese
populations, Silent substitution rates of 0.0011 and 0.0017
substitutions per site per year were observed in the NS5 and E1
regions by sequence comparisons from a cohort of individuals
infected from a common source of infection 17 years previously.
Mean silent substitution frequencies of 0.169 and 0.224 in NS5 and
E1, respectively, were observed amongst type 1b variants infecting
epidemiologically unrelated individuals from several countries,
This predicted a time of divergence from a common ancestor of 64-69
years, The absence of country-specific groupings by phylogenetic
analysis of these sequences suggested that the spread of this
genotype occurred on a worldwide basis at a similar time. Dates for
the spread of other genotypes varied from around 80 years (type 2a)
to 54 years (type 3a), suggesting that different variants spread
into communities at different times this century. By extrapolating
the silent substitution rater the time of divergence of type 1a
from 1b can be estimated at 200-300 years, but even this is likely
to be an underestimate of the true time due to inequalities on the
transition and transversion ratios, and the greater frequency of G
<-> A transitions, compared with C <-> U, which are not
considered in the current analysis. Thus, the diversity of the
globally distributed genotypes such as type 1b and 3a suggests a
relatively recent origin for HCV in Western countries and Japan,
and contrast with the much greater diversity of specific genotypes
in Central Africa (type 4) and South East Asia (type 6), These data
may assist in understanding the global epidemiology of HCV and the
mechanisms by which it has spread.
Author: SIMMONDS P, UNIV EDINBURGH, DEPT MED MICROBIOL,
TEVIOT PL, EDINBURGH EH8 9AG MIDLOTHIAN
Source: JOURNAL OF VIRAL HEPATITIS 1997 ;4:69-74
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