Virus variation

[Bruce Phillips]

     My recent provocative (?) contribution addressed mechanisms
for generating antigenic diversity in virus progeny.  Perhaps I
overstated the case for HIV when I said that the mutation rate was
several point mutations per genome replicated, but based on error
rates for HIV RT, it is 1-2 per genome replicated.  That many of
these mutations get fixed- i.e., become viral genomes in infectious
virus particles- is evident from the huge diversity of antigenic
strains formed in a single patient and during tissue culture
passage.  Parenthetically, some theoreticians published a paper in
Science in which a consideration was given to the effect that, in
a given individual, the number of HIV variants produced might
exceed the repertoire of antibodies that that individual's immune
system was capable of producing.  That is, the final collapse of
the immune system might result from the last variant produced for
which there was no (effective) immune response.  Such a
consideration was never contemplated, as far as I know, for any
other virus infection.
 
     My recollection of error rates for RNA virus transcriptases is
that HIV is an order of magnitude LESS faithful than other RNA (+)
or RNA (-) transcriptases.  If that is wrong, I'd like to hear
about it.
 
     I did not mean to imply that recombination does not play a
significant role in generating diversity in influenza viruses- but
it does not seem to play a role in any given virus's ability to
escape immune response ONCE INFECTION OCCURS.  Without question,
genetic shift accounts for the appearance of flu viruses for which
pre-existing immunity (or cross-immunity) doesn't exist.
 
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