XMRV explained By CFIDS scientific Director, taken from Facebook post

[Guest guest]

By Suzanne D. Vernon, PhD

Scientific Director, the CFIDS Association of America

Suzanne Vernon, PhD

The announcement on October 8, 2009, that an infectious retrovirus called XMRV

(xenotropic murine leukemia virus-related virus) was linked to CFS, could be the

game-changing scientific event we have been waiting for. Whether XMRV provides

the long-awaited causal link will depend on the findings described in the

Science paper being replicated by another laboratory in another group of CFS

patients. To help clarify what we know, let's review the findings.

Dr. Judy Mikovits and her team at the Whittemore Institute for

Neuro-immune Disorders (WPI) made a very insightful connection three years ago.

XMRV was first described in prostate cancer in 2007 by investigators at the

Cleveland Clinic, who also reported that XMRV-positive prostate cancer patients

have alterations in RNase L, an antiviral immune system pathway. The WPI

investigators knew that RNase L activity is also altered in blood cells from CFS

patients and they made the decision to look for XMRV in CFS patients with this

immune defect.

When scientists want to find a virus, we look for it in the sickest individuals

because often this is where there is likely to be the highest levels of a virus,

if present. Dr. Dan has been caring for and researching CFS patients

since the 1984 Incline Village outbreak, so he identified CFS patients with

prolonged disabling fatigue, cognitive impairment, and documented laboratory

immunological abnormalities (including altered RNase L activity) to hunt for

XMRV.

The WPI laboratory team detected XMRV sequences in 68 of 101 (67%) CFS patients

tested and in 8 of 218 (3.7%) healthy control subjects. The Cleveland Clinic

confirmed the presence of XMRV in a subset of these same CFS cases, 7 of the 11

samples from WPI. The Cleveland Clinic researchers found that the CFS XMRV was

similar to prostate cancer XMRV, and not a mouse virus (murine leukemia virus)

that could have been a contaminant explaining the discovery.

The investigators designed several laboratory tests to understand XMRV. They

looked to see if XMRV was expressed in peripheral blood mononuclear cells

(PBMCs) of CFS patients. PBMCs circulate throughout the entire system and can be

important " sentinels " for processes occurring in the body. PBMCs from 19 of 30

CFS patients expressed XMRV proteins compared to 0 of 16 PBMC samples from

healthy controls. They also wanted to know which cells harbored XMRV; they found

it in T and B cells in the blood of one CFS patient. The investigators looked to

see if the XMRV from CFS patients was infectious. Both blood cells and plasma

(the cell-free fraction of blood) from XMRV-positive CFS patients were able to

transmit this virus to a susceptible cell line, indicating the virus could be

transmitted in laboratory culture. Finally, they wanted to know if XMRV

stimulated the immune system to produce antibodies. Plasma from 9 of 18 CFS

patients had antibodies that reacted with a virus protein similar to that found

in XMRV, compared to no reaction from plasma of 7 healthy controls.

This Science paper tells us that XMRV plays a possible role in CFS pathogenesis

in these CFS patients. How much we can generalize these findings to other CFS

patient populations? That answer will depend on the results of replication

studies.

The design of replication studies should include CFS patients who are similar to

those selected by Dr. and reported in the Science study. Unfortunately,

the details about the CFS patients were not sufficient to enable independent

investigators to select similar CFS patients. For example, we need to know the

age, sex, duration of illness, medical history, and medication use – to name a

few characteristics – of the studied patients to select CFS patients who are as

similar as possible to the original group. We also need to know something about

the healthy control subjects, since there is nothing in the paper or

supplemental materials that describes how they were selected. Independent

replication studies should also include patients with mild and moderate CFS, at

least one chronic disease control group (e.g., multiple sclerosis, lupus) and

sex and age-matched healthy controls. We are actively working with several

independent research groups to expedite these studies.

While these exciting studies of XMRV continue, the CFIDS Association continues

its support of our funded investigators. It's important to remember that HIV was

first linked to AIDS in 1983, yet worldwide research on HIV continues today. Our

funded investigators' research on why Epstein-Barr virus (EBV) triggers CFS,

whether ion-channel receptors are markers of fatigue, why CFS patients have

higher rates of leaky gut, why CFS patients have slow blood flow to the brain,

why CFS patients have metabolic disturbances in the brain, and how we can bring

this information, as well as XMRV, together using powerful computational tools

are all important as we work together to solve CFS.

References:

Detection of an infectious retrovirus, XMRV, in blood cells of patients with

chronic fatigue syndrome. Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen

KS, DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M,

Silverman RH, Mikovits JA. Science 8 October 2009. 1179052.

Supporting online material for Detection of an infectious retrovirus, XMRV, in

blood cells of patients with chronic fatigue syndrome. Lombardi VC, Ruscetti FW,

Gupta JD, Pfost MA, Hagen KS, DL, Ruscetti SK, Bagni RK,

Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Science 8 October

2009.

A new virus for old diseases? Coffin JM and Stoye JP. Science 8 October 8 2009.

Information about the Association's research program:

http://www.cfids.org/about/acceleratecfsresearch.asp