Risk assessment of the XMR virus and XMRV-infected cell lines

In 2006, a new gammaretrovirus was discovered during the investigation of human prostate carcinomas, which was identified due to its similarity to xenotropic murine Gammaretroviruses as xenotropic murine leukemia virus-related virus (XMRV). The initially postulated connection between an XMRV infection and the development of Prostate cancer or chronic fatigue syndrome (also known as myalgic encephalomyelitis, ME/CFS) has since been refuted. Currently, there is no reliable evidence for a correlation between XMRV infection and disease in humans or animals. XMRV is an enveloped gammaretrovirus whose RNA genome was probably generated by homologous recombination between two endogenous murine gammaretroviruses during serial passenger transport of a human prostate tumor in immunosuppressed laboratory mice. Only the genomes of the late passages of the tumor and the genomes of the final genomes from these established Cell lines CWR22Rv1 (22Rv1) and CWR-R1 contain copies of the XMRV provirus. Cell culture experiments demonstrate that XMRV can infect human epithelial cells, such as those of the prostate and kidney, as well as lymphocytes. In animal experiments, macaques could be infected with XMRV. However, the infected animals showed only short-term viremia and no signs of disease.

In TRBA 462 "Classification of Viruses into Risk Groups," XMRV is assigned to risk group 1 with the suffix "t21" (vertebrate pathogen). In TRBA 468 "List of Cell Lines and Activities with Cell Cultures," the cell line 22Rv1 is assigned to risk group 1.

According to Section 5 (1) GenTSV in conjunction with the criteria in Annex 1 GenTSV, the ZKBS classifies XMRV and the cell lines 22Rv1 and CWR-R1 as donor and recipient organisms for genetic engineering work in its statement of April 2022. Risk group 2 The rationale states that XMRV is an exogenous murine gammaretrovirus that can infect human cells and macaques. During the viral replication cycle, viral cDNA is integrated into the genome of infected cells, resulting in Insertional mutagenesis cannot be ruled out. The 22Rv1 cell line secretes infectious, replication-competent XMRV particles, and this cannot be ruled out for CWR-R1 either. The XMRV particles thus determine the hazard potential of these cell lines.

The ZKBS statement can be found at File number 6790-05-04-0042 can be retrieved.