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Multiplicity of retrovirus infection and integration?

Paul Kowalski kowalski at stanford.edu
Wed Aug 11 12:05:03 EST 1999


In case anyone's interested- here are a few other refs that helpful people
have emailed me:


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 Our group has looked at the effect of MOI on retrovirus transduction.
More than one integrative event per cell can definitely occur, however,
the maximum number of events is a function of the initial active
retrovirus concentration and the number of target cells. As retroviruses
decay (half life ~7 hrs for murine leukemia viruses), the "million"
viruses don't all have the opportunity to infect the "one" target cell
before they are inactivated. Two papers you might want to take a look
at:

Morgan et al., "Retrovirus infection: effect of time and target cell
number."
J Virol. 1995 Nov;69(11):6994-7000.

LeDoux et al., "Kinetics of retrovirus production and decay."
Biotechnol Bioeng. 1999 Jun 20;63(6):654-62.
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Porter et al. 1996.  Comparison of efficiency of infection of human gene
therapy target cells via four different retrooviral receptors. Human Gene
Therapy 7:913-919
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Check Scadden and Cunningham, J Virol, 1990 or so. In one clonal cell line,

they achieved 14 integrations with the retroviral vector and a similiar
number of integrations with a defective provirus that is also packaged into

the defective particle.


Enjoy-

PK


Paul Kowalski wrote:

> Hi -
>
> does any bionetter know of any papers discussing how often a given human
> or mouse cell can be infected by a integrative retrovirus? I.e. if you
> put 1 cell in a dish with a million retroviruses, how many integrations
> would you see? Also, I'm thinking of retroviral vectors here, so
> resistance to superinfection wouldn't be a issue. I've seen a paper from
> JC Burns group (Methods Cell Biol 1994;43 Pt A:99-112 ) mentioning that
> the env pseudotype matters- that generally cells infected with a high
> MOI of amphotropic virus only get 1 integration/cell, but they saw up to
> 4 integrations/cell with a VSV-G pseudotype, which they chalked up to
> the higher titers of VSV-retrovirus.
>
> If anyone knows any other literature regarding this, I'd really
> appreciate knowing! Thanks in advance-
>
> Paul Kowalski
> Postdoctoral Fellow - Genetics Dept.
> Stanford University School of Medicine
> kowalski at stanford.edu





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