Reverse transcriptases

[Olav Hungnes]

Patrick O'Neil (patrick at corona) wrote:


: On 24 May 1995, Bruce Phillips wrote:

: > 
: > 	The error-proneness of lentivirus RTs are clearly documented.  Does
: > anyone with expertise in something other than guns know if there are 
: > experimental data concerning the error-proneness of oncovirus RTs?  While
: > this isn't my field of expertise, I don't recall ever hearing about RTs
: > lack of fidelity until HIV came along.

: All RTs from all retroviruses tend to be highly error-prone.  The lab I 
: am in works with HIV RT and Murine Leukemia Virus RT.  They both 
: demonstrate about the same error rate of about 10^-5 per base per 
: replication cycle.

: The actual focus of the lab in regards to both is error rate.  We are 
: looking at the difference between error rates in vitro vs that seen in 
: vivo.  With MLV, the in vivo error rate is about 30-fold lower than 
: predicted by in vitro assay, implying either other viral encoded or host 
: cell supplied proteins that increase fidelity somewhat.  Nevertheless, 
: the in vivo error rate of 3 x 10^-5 mutations per base-pair per 
: replication is about the norm for others:  Rous Sarcoma Virus 
: demonstrates an error rate in vivo of about 1.4 x 10^-5 per base-pair per 
: replication.  Spleen Necrosis Virus has an error rate of 0.7 x 10^-5.  In 
: general, the error rates for RTs from any sampling of retroviruses range 
: from 2.5 x 10^-5 to 6 x 10^-5.  Basically, you can count on about 0.5 
: base substitutions per retroviral genome per replication.  These rates do 
: not include other errors such as deletions or insertions due to slippage 
: on repetitive sequences.

: Patrick

I think one should keep in mind that the other side of the retrovirus
replication cycle, transcription from proviral DNA by host cell
RNA polymerase II, is probably also error-prone. The retrovirus
has little to gain from evolving an RT with significant higher 
fidelity than the RNA poly. Last time I read about this there was little 
documentation on the fidelity of RNA polymerases. Anyone have info on 
this? 

-- 
_______________________________________________________
Olav Hungnes                 olav.hungnes at embnet.uio.no
National Institute               Phone  (+47)22042200
of Public Health                 FAX    (+47)22353605
Oslo, NORWAY
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