Re: Retroviral vectors

From: Donald E. Mosier (dmosier@scripps.edu)
Date: Wed Jan 27 1999 - 14:04:04 EST


The current retrovirus vectors used for gene expression in human cells are
based either on mouse retroviruses (typically Moloney mouse leukemia virus)
or on primate lentiviruses including HIV.  All such systems use defective
virus genomes that are packaged into infectious particles that are only
capable of a single round of replication.  The only defined safety concern
is that these defective virus genomes might potentially be rescued by what
is called a helper virus if that replication competent virus were to infect
the same cell.  This has happened in early monkey trials of mouse
retrovirus-mediated gene transfer, and the helper virus was an endogenous
monkey retrovirus.  Since no replication competent endogenous human
retroviruses are known, the risk of this happening in humans is thought to
be remote.  There are human endogenous retrovirus sequences (HERV)
dispersed through the human genome, but none of these encodes a complete
virus sequence.  These is a very remote possibility that activation of one
of these HERV sequences could complement what is missing in the original
retrovirus vector (typically the envelope gene).  In short, the biohazard
posed by retrovirus-transduced human cells is very, very low but
potentially not zero.  It is much more important to know if the human cells
harbor HIV or hepatitis B or C in terms of biohazard risk.  Our laboratory
handles such cells under BSL-2 conditions, and flow cytometry is performed
on fixed samples (1% paraformaldehyde for 30 min.).

Donald Mosier


>Dear Flow Group,
>
>Could someone please bring me up to speed on sorting human cells infected
>with retrovirus which are used for research purposes?  I understand that
>these reagents are supposed to be defective viruses used for genetic
>transfer.  What biohazard classification has a laboratory working with these
>vectors?  What precautions over and above the common practices are required?
>Will bleaching through the sample probe between sorts eliminate viruses from
>the flow cytometer to prevent viral contamination of subsequent sorts?
>
>Please cite references if available.  Can someone cite a reference that
>lists the requirements for laboratories according to the different biohazard
>classifications?
>
>Thanks in advance,
>Sue Rice
>

______________________________________________________________________________
Donald E. Mosier, Ph.D., M.D.
Department of Immunology IMM7
The Scripps Research Institute
10550 N. Torrey Pines Road
La Jolla, CA 92037

619 784-9121 voice
619 784-9190 fax



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