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mutation
Nov 11, 2002

Dear doctors:

Here is quotations from a website:

"the HIV virus is 9,128 bases long." "HIV I reverse transcriptase is extremely tolerant of non-standard base pairs and modified ribose units. This leads to an extremely high rate of mutation on the HIV genome. This is compounded by the fact that reverse transcriptase has no exonuclease capability, and hence no way to "proofread" strands of nucleotides as they are being produced. The rate of mistakes averages about 1/1700 to 1/4000 bases, but evidence points that reverse transcriptase is selectively unfaithful, as some bases in the genome have error rates as high as 1/30 bases! (3) One estimate suggests that about 10 bases change in the HIV genome per replication cycle! This high rate of mutation is the major obstacle in the search for a truly effictive wonder drug or vaccine to combat HIV, as resistant strains of the virus evolve rapidly. " End of quotation.

If most of mutation is bad mutation for virus and will lead to death of virus, does the data above imply that most virus can not generate their children at all after their entering into the CD4+ cells? Thank you. Mark

Response from Dr. Wohl

Here is exactly teh problem - not all mutations are fatal to the virus. The virus is very sloppy in making more of itself but can survive even with major mutations.

Offspring viruses can have varying degrees of difference from the 'parent' virus with some being only be slightly different and others much more so.

Add some HIV drugs to the mix and the mutations selected will be those that favor survival in the face of the presence of the drug. Lots of mutations but the bugger stick keeps ticking.

So, unfortunately, HIV does continue to replicate after entering T-cells. Its sloppiness makes the virus infection harder to treat and harder to prevent. DW



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