Missing env region in the 22Rv1 XMRV virus
Several papers such as Paprotka (2011) and Hue (2011) have claimed that the positive results from all studies finding murine leukemia virus-related viruses are the result of contamination from a virus they say was created in a cell line called 22Rv1.
These are cells created from the tumor of a potentially infected prostate cancer patient. They claim that this virus only ever infected other cell lines, is not in lab mice, and is not the reason for the positive results.
However, looking at the data placed into the Genbank we can see that only one complete genome of this virus has been sequenced, but no data on the env gene has been included. Furthermore, the cell line this sequence was taken from is not said to be 22Rv1 alone, but is /cell_line="22Rv1/CWR-R1". What sections of this virus were taken from the 22Rv1 cells alone and what was from CWR-R1 cells?
The sequence can be found here.
http://www.ncbi.nlm.nih.gov/nuccore/334717372
If you select the "Graphics" tool in the top left you can see there is no env gene available. (A comparison of other Xenotropic MuLV-related virus complete genomes is provided at the end of this article.)
As you can see there is data for the viruses gag-pro-pol gene. But there is NO such data for the env gene.
There is also no homology between the amino acids translated from the 22Rv1/CWR-R1 virus and VP62.
"Exact peptide matches to XMRV proteins spanned 54% of the Gag, 47% of the Gag-Pro-Pol, and 33% of the Env protein sequence. A BLAST search of the GenBank database using the compiled peptide sequences revealed perfect or near-perfect matches to the existing XMRV isolates, with lower similarity to any other retroviruses in the database." - Knouf et al., 2009.
This could easily be a closely related MLV or even a different human MLV entirely.
This sequence was placed in the Genbank by the authors of Paprokta (2010). During this study the authors also worked with the synthetic plasmid VP62, a virus that could have infected the 22Rv1 cell line. At no time did the authors test for VP62 plasmid contamination, they only assumed the virus in the cell line was XMRV.
Sequencing by Knouf et al. (2009) and Hue et al. (2010) has also shown there are differnt gamma retrovirus gag genes in the 22Rv1 cell line, indicating the presence of at least three different XMRVs, with a homolgy ranging from 98% to 96%.
Dr Coffin and others believe this virus was responsible for contaminating patients clinical samples, but there is no evidence that a complete virus is present in the 22Rv1 cell line.
REFERENCES
- Knouf et al. Multiple Integrated Copies and High-Level Production of the Human Retrovirus XMRV (Xenotropic Murine Leukemia Virus-Related Virus) from 22Rv1 Prostate Carcinoma Cells. 2009. Journal of Virology. DOI: 10.1128/JVI.00546-09
- Hue et al. Disease-associated XMRV sequences are consistent with laboratory contamination. 2010. Retrovirology. DOI:10.1186/1742-4690-7-111.
- Paprotka et al. Multiple Integrated Copies and High-Level Production of the Human Retrovirus XMRV (Xenotropic Murine Leukemia Virus-Related Virus) from 22Rv1 Prostate Carcinoma Cells. 2010. Journal of Virology. DOI:10.1128/JVI.00546-09.
