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General Information About Mammalian Virus Vectors

All use of mammalian recombinant virus vectors at UR must be approved by the IBC through the registration process. Non-mammalian vectors (such as baculovirus) are exempt from this requirement.

Please note that the NIH Guidelines stipulate that Institutional Biosafety Committee approval be obtained prior to use of recombinant mammalian virus vector systems. See NIH Guidelines Section III-D.

Overview of selected vector systems

General comment on containment: Suggested biosafety containment levels are provided for each vector system. Note, however, that use of a higher-level containment facility may be required in some cases, depending on the specific properties of the vector and/or insert. Special care should be given to the design, risk assessment (Section 2 of NIH Guidelines), and handling of virus vectors containing genes that make growth-regulating products, products released into the circulation, products that may have a general effect on the host-immune system.

Adenovirus: Adenoviruses are infectious human viruses, which often cause mild respiratory illness. Rare cases of severe disease can occur, and its use as a genetic vector therefore requires the use of adequate containment equipment and practices. Biosafety Level 2 (BL2) is appropriate for many constructs (see above). Particular care should be given to vectors containing genes that make products that may be similar to products made by the deleted adenovirus genes.

Adeno-associated virus: These are infectious human viruses with no known disease association. Some AAV types are common in the general population, and these viruses have the ability to integrate into the host chromosome. The NIH Guidelines (Appendix B) state that "adeno-associated virus (AAV) types 1 through 4, and recombinant AAV constructs, in which the transgene does not encode either a potentially tumorigenic gene product or a toxin molecule and are produced in the absence of a helper virus" can in most cases be handled at biosafety level 1 (BL1). This level of containment made is modified by other considerations (see above).

Herpesvirus: Herpesviruses include infectious human viruses such as herpes simplex virus type-1 (HSV-1), which is the most commonly used vector system. HSV-1 is common in the general population, but can cause encephalitis in rare cases; its utility as a vector system stems from its broad host cell range, ability to transduce neurons, and its large insert capacity. Biosafety Level 2 (BL2) is appropriate for many constructs (see above).

Lentivirus: Lentiviruses are a subset of retroviruses, with the ability to integrate into host chromosomes, and to infect non-dividing cells. These viruses can cause severe immunologic and neurologic disease in their natural hosts. Lentivirus vector systems can include viruses of non-human origin (feline immunodeficiency virus, equine infectious anemia virus) as well as simian viruses (simian immunodeficiency virus) and human viruses (HIV). Typical lentivirus vectors take the form of virus pseudotypes bearing envelope proteins from vesicular stomatitis virus (VSV). It is usually recommended that work with non-human lentiviruses that are incapable of establishing productive infections in humans (FIV, EIAV) be conducted at biosafety level 2 (BL2). Work with simian or human lentiviruses (SIV, HIV) is typically conducted at a higher containment level (please consult the IBC).

Poxvirus: Poxvirus vectors include avian viruses (avipox vectors) such as NYVAC and ALVAC, which cannot establish productive infections in humans, as well as mammalian poxviruses, which can productively infect humans -- such as vaccinia virus and modified vaccinia viruses (MVA). Poxviruses are highly stable, and vaccinia virus can (rarely) cause severe infections in immunocompromised persons, persons with certain underlying skin conditions, or pregnant women. Such individuals should not work with vaccinia virus (see IBC guidelines). The use of biosafety Level 2 (BL2) is appropriate for many poxvirus and constructs (see above).

Retrovirus: These are infectious viruses which can integrate into transduced cells with high frequency, and which may have oncogenic potential in their natural hosts. Retrovirus vector systems are typically based on murine viruses -- most commonly, these systems include ecotropic viruses (which can infect only murine cells), amphotropic viruses (which can infect human cells) or pseudotyped viruses (which can also infect human cells). Containment for vectors with the ability to infect human cells will usually be recommended at biosafety level 2 (BL2), as per the NIH Guidelines (Appendix B) ("For agents that are infectious to human cells, e.g., amphotropic and xenotropic strains of murine leukemia virus, a containment level appropriate for RG2 human agents is recommended."), whereas for ecotropic vectors with no ability to infect human cells, BL1 containment may be appropriate ("[ecotropic] murine retroviral vectors....that contain less than 50% of their respective parental viral genome and that have been demonstrated to be free of detectable replication competent retrovirus can be maintained, handled, and administered, under BL1 containment").

Baculovirus: Non-mammalian virus vectors are exempt from these registration requirements.

This page last updated 4/25/07. Disclaimer