Codons and HIV

Jay Mone' jmone at MARAUDER.MILLERSV.EDU
Mon Mar 16 11:14:18 EST 1998


HIV has 400,000 plus codons???  A 10,000 base RNA could contain only 
3,300 codons, since a codon is composed of 3 nucleotides.  This, of 
course, doesn't account for frame shifting, which would increase the 
codon number to a maximum of 9,000 codons.  This also doesn't take 
into account the fact that a significant portion of the HIV genome is 
not translated, but serves regulatory functions (for example, the 
LTRs).
The main reason that you get colds regularly isn't because the cold 
viruses continually mutate.  The mutation rates of picornaviruses are 
actually rather low.  Why do you think the polio vaccine has retained 
it's effectiveness?  The real reason is that there are over 100 
serotypes of rhinoviruses which can cause colds, and there is little 
immunologic cross-reactivity between serotypes.  In addition, there 
are many other viruses which cause symptoms similar to colds, also 
which don't cross react.
The real trick of mutations is that the mutations must confer a 
selective advantage in order for the virus to survive.  Many mutations 
which occur in HIV are lethal mutations, which is why some portions of 
the HIV genome appear to be highly conserved, while other regions show 
plasticity.
The blood test for HIV used in blood banks tests not for the presence 
of virus, but the presence of antibodies against the virus, which is 
why there is a window where an infected person may test negative, but 
actually is infectious.  The antibodies tested for are not those 
directed against the hypervariable epitopes of the envelope, but those 
directed against conserved sequences of the capsid, p24, which show no 
change from strain to strain.  Why?  Probably because capsid mutations 
are lethal, so even though they occur, the virus doesn't survive.  The 
current estimates of the chances of becoming infected from a blood 
transfusion are about 1 in 1 million, according to the AABB.  This is 
compared to 1 in 63000 for HBV, which doesn't mutate at an appreciable 
rate.  Not bad, huh?
Tom, you are example of how a little knowledge can be worse that 
complete ignorance.  Do your homework before you start discoursing on 
molecular biology and epidemiology.  Be part of the solution, not part 
of the problem.

Jay M.



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