15th International Conference on Human Retroviruses: XMRV infection results in dysregulation of the immune response

Immune correlates of XMRV infection
Lombardi et al. Retrovirology 2011, 8(Suppl 1):A221
Published: 6 June 2011


Vincent Lombardi1, Deborah Goetz2, Max Pfost1, Cassandra Puccinelli1, Judy Mikovits1*:

From 15th International Conference on Human Retroviruses: HTLV and Related Viruses
Leuven and Gembloux, Belgium. 5-8 June 2011

Author details
1Whittemore Peterson Institute, Reno, NV, 89557, USA. 2Environmental
Sciences,University of Nevada, Reno, NV, 89557, USA.


Background
CFS patients often display antiviral enzyme RNase L dysfunction
underscoring the importance of the innate
immune response in CFS. We reported the XMRV detection
in the peripheral blood of 67% of a cohort of CFS
patients and 3.4% of controls [1]. XMRV infection may
play a role in CFS pathogenesis through the dysregulation
of the immune response.
Methods
This hypothesis was addressed by multiplex profiling of
plasma cytokines and chemokines on a LuminexTM platform
and phenotypic analysis of leukocyte subsets by
multi-parameter flow cytometry in XMRV infected CFS
patients versus uninfected controls. XMRV-infected subject
and control samples were assayed blindly. Analysis
was performed using the Gene Expression Pattern Analysis
Suite and Random Forest tree classification algorithms.
For immune profiling, 63 XMRV infected CFS patient
samples were analyzed within 6 hours using an LSRII flow
cytometer with BD FACSDiva software. Six normal donors
and reference values based on a healthy population were
used as normal baselines.

Results
16 of the 26 cytokines/chemokines measured were significantly
differentially expressed; eleven up-regulated and
five down-regulated including: IL-8, IL-6, MIP1alpha,
MCP-1, IFNalpha and TNFalpha. XMRV-infected CFS
patients showed reduced percentages of CD56+ NK and
CD19+ B cells. The NK phenotype in XMRV-infected
CFS patients was altered, with 80% of the patients having
a significantly reduced CD56+DIM population. The B
cells present in the peripheral blood were CD20+, CD23
+ mature B cells.

Conclusion
XMRV infection results in dysregulation of the immune
response, either directly by infection of specific leukocyte
subsets or indirectly through cytokine modulation.