Safety Data Sheet - Infectious Substances
Section I - Infectious Agent
Name: Moloney Murine Leukemia Virus (MoMuLV) recombinant vectors
Characteristics: Retroviridae; subfamily oncovirinae type C, enveloped, icosahedral core, virions 100 nm in diameter, diploid, single stranded, linear RNA genome. MoMuLV integrates into the host genome and is present in infected cells as a DNA provirus. Cell division is required for infection. Virus is not lytic. Vectors produced in the Vector Development laboratory are designed to be replication incompetent.
Biosafety Level: NIH BSL 2
Section II - Health Hazard
Pathogenicity: Wild type virus is oncogenic in mice. In rhesus monkeys, lymphomas were observed several months after autologous transplantation of bone marrow stem cells transduced with a retroviral vector preparation containing replication competent virus. The data suggests a pathogenic mechanism in which chronic productive retroviral infection allowed insertional mutagenesis leading to cell transformation and tumor formation. To date, no documented clinical manifestations of disease have been noted in humans exposed to MoMuLV vectors. There is a risk of insertional mutagenesis. The nature of the transgene or other introduced genetic element may pose additional risk.
Host Range: The host range of recombinant MoMuLV vectors is dependent on the specificity of the viral envelope. The ecotropic env gene produces particles which infect only murine cells. Amphotropic env allows infection of murine and nonmurine cells, including human cells. VSV-G envelope allows infection in a wide range of mammalian and non-mammalian cells.
Mode of Transmission: MoMuLV infects only actively dividing cells. In mice, the virus is transmitted in the blood from infected mother to offspring. Transmission may also occur via germline infection. In vivo infection in humans appears to require direct injection with amphotropic or pseudotyped virus.
Incubation Period: Disease in mice is the result of relatively rare integration events and is reflected in a relatively long lag time between infection and tumor formation. For example, thymic lymphomas are seen only after 3 months following infection of new born mice with MoMuLV. No disease noted to date in humans.
Section III - Viability
Drug susceptibility: No specific anti-viral available. No recommended treatment.
Susceptibility to Disinfectants: Susceptible to 1% sodium hypochlorite, 1% SDS, 70% ethanol. Recommend fresh solution of 10% bleach for 15 minutes.
Physical Inactivation: Sensitive to heat (store at -70 oC), desiccation.
Survival Outside of Host: Viral particles are extremely labile and do not survive on environmental surfaces
Section IV - Medical
Surveillance: Pre-employment serum samples banked. Monitor for symptoms specific to transgene exposure if indicated. Infection can be confirmed by detection of provirus.
First Aid/Treatment: For splashes to the eye of material containing virus, rinse eye at eyewash for 15 minutes. Recommend new serum sample be taken and stored immediately after accidental injection or mucous membrane exposure. In the case of accidental injection of material containing virus, wash area well with soap and water then contact office of Occupational Health and request serum sample (UCSD Occupational Health 274-6206). At UCSD, notify supervisor and EH&S as soon as possible after exposure.
Immunization: None available.
Prophylaxis: None available.
Section V - Laboratory Hazards
Laboratory- acquired infections: None documented.
Sources/Specimens: Theoretical risk from exposure to laboratory cultures of wild type virus or recombinant virus.
Primary Hazards: Direct injection.
Special Hazards: Contact with feces or urine from infected animals for 72 hours post infection. Contact with tissues and body fluids of infected animals.
Section VI - Recommended Precautions
Containment Requirements: Biosafety level 2 practices and BSL 2 containment facilities for all activities involving the virus, recombinant virus vectors, and potentially infectious body fluids or tissues.
Protective Clothing: Laboratory coat, gloves.
Section VII - Handling Information
Spills: Allow aerosols to settle for 15 minutes; wear protective clothing and gently cover the spill with adsorbent paper towel and apply freshly prepared 10% sodium hypochlorite starting at the perimeter and working towards the center; allow at least 15 minutes contact time before clean up.
Disposal: Decontaminate all wastes before disposal; steam sterilization, incineration, chemical disinfection. At UCSD contaminated material may be sealed in labeled, doubled, red biohazard bags and transported in covered, leak proof containers to BFI disposal bins for eventual incineration.
Storage: In sealed containers that are appropriately labeled and in approved locations for BSL 2 materials at -70oC.
Transport: Material must be sealed in primary and secondary containers, appropriately labeled.
Section VIII - Transgened and Other Foreign Genetic Elements
Considerations: What is the replication status of the vector? In general, recombinant MoMuLV vectors produced in the Vector Development laboratory are replication incompetent. What is the nature of the transgene/s - are any potentially hazardous transgenes expressed, i.e.. toxins, oncogenes? Have any foreign elements been introduced which alter the specificity, host range, stability, or titer of the resulting vector?
It is imperative that those handling recombinant vectors consider both the nature of the virus used as a vector and the effects of any transgene, introduced genetic elements, or other modification.
Prepared by UCSD Program in Human Gene Therapy staff. Reviewed by UCSD Office of Environmental Health Safety. We accept no responsibility for the accuracy, sufficiency, or reliability of this information or for any loss or injury resulting from the use of this information. (written August 20, 1998)