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Abstract
BackgroundXenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV.ResultsImmunization elicited Env-specific binding and neutralizing antibodies (NAb) against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1∶1024 and 1∶464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.ConclusionsVaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.
Highlights
Xenotropic murine leukemia virus-related virus (XMRV) was first identified through microarray analysis of human prostate cancer (PC) samples from patients with an inherited defect in RNASEL (R462Q variant), a downstream effector of the antiviral interferon defense pathway [1,2]
This study showed concordance between the presence of neutralizing antibodies (NAb) and XMRV nucleic acids detected by nested PCR and FISH
The results indicated that the XMRV pseudovirus is,250 times more infectious than the control HIV-1 pseudovirus
Summary
Xenotropic murine leukemia virus-related virus (XMRV) was first identified through microarray analysis of human prostate cancer (PC) samples from patients with an inherited defect in RNASEL (R462Q variant), a downstream effector of the antiviral interferon defense pathway [1,2]. This study showed concordance between the presence of neutralizing antibodies (NAb) and XMRV nucleic acids detected by nested PCR and FISH Another independent study has shown that XMRV is detectable in normal and tumor prostate tissue from patients with PC from the southern United States [7]. In addition to being identified in PC samples, evidence for XMRV was found in a study of subjects with Chronic Fatigue Syndrome (CFS) that revealed the presence of XMRV in activated human B and T cells as well as detectable levels of anti-XMRV Env antibodies in nine out of 18 CFS human plasma samples [8] In another recent study, a second related polytropic MLV-like virus was detected in separate cohort of 37 CFS subjects [9]. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV
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