J Virol. 2010 Nov 17
Sakuma T, Department of Molecular Medicine, Mayo Clinic, College of Medicine, Rochester, MN 55905 USA
A novel gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), has been identified in patients with prostate cancer and in patients with chronic fatigue syndromes.
Standard Mus musculus laboratory mice lack a functional XPR1 receptor for XMRV and are therefore not a suitable model for the virus.
In contrast, Gairdner's Shrew-mice (Mus pahari) do express functional XPR1. To determine if Mus pahari could serve as a model for XMRV, primary Mus pahari fibroblasts and mice were infected with cell-free XMRV.
Infection of cells in vitro resulted in XMRV Gag expression and the production of XMRV virions.
After intraperitoneal injection of XMRV into Mus pahari mice, XMRV proviral DNA could be detected in spleen, blood, and brain.
Intravenous administration of a GFP vector pseudotyped with XMRV produced GFP-positive CD4-positive T cells and CD19-positive B cells. Mice mounted adaptive immune responses against XMRV as evidenced by the production of neutralizing and Env- and Gag-specific antibodies.
Prominent G-to-A hypermutations were also found in viral genomes isolated from the spleen suggesting intracellular restriction of XMRV infection by APOBEC3 in vivo.
These data demonstrate infection of Mus pahari by XMRV, potential cell tropism of the virus, and immunological and intracellular restriction of virus infection in vivo.
These data support the use of Mus pahari as a model for XMRV pathogenesis and as a platform for vaccine and drug development against this potential human pathogen.