Viruses in the News

I saw very interesting report a couple of days ago - about a murine (mouse) virus that had been implicated in some types of prostate cancer.  Based on just released research findings it seems this virus  may also be the cause of chronic fatigue syndrome (sometimes known as ME or myalgic encephalomyelitis, or nicknamed “yuppie flu”).  A surprisingly large number of people may have been infected with this virus without even knowing about it.   Here are some quotes from the WebMD article as well as link to the full article.  

Retrovirus Linked to Chronic Fatigue Syndrome

XMRV Seen in 2/3 of CFS Patients; 10 Million in U.S. May Carry Virus

By Daniel J. DeNoon

Oct. 8, 2009 - Some 10 million Americans may carry a recently discovered retrovirus now linked to chronic fatigue syndrome.

The virus, xenotropic murine leukemia virus-related virus or XMRV, was detected in 67% of 101 patients with chronic fatigue syndromeby Vincent C. Lombardi, PhD, of the Whittemore Peterson Institute in Reno, Nev., and colleagues.

The researchers also found the virus in nearly 4% of healthy comparison subjects — suggesting that millions of Americans may carry the mysterious virus, which was first detected in prostate cancers.

The discovery of XMRV in two major diseases, prostate cancer and now chronic fatigue syndrome, is very exciting. If cause and effect is established, there would be a new opportunity for prevention and treatment of these diseases,”said Robert H. Silverman, PhD, of Cleveland Clinic’s Lerner Research Institute, in a statement emailed to WebMD.

Where did the virus come from? The virus is closely related to a retrovirus that’s become part of the mouse genome. Oddly, XMRV cannot infect mouse cells — but can easily infect human cells. It’s unlikely that so many humans have caught XMRV from mice. It’s more likely that the virus is spread from human to human, but how that happens remains to be seen.

“If these figures are borne out in larger studies, it would mean that perhaps 10 million people in the United States and hundreds of millions worldwide are infected with a virus whose pathogenic potential for humans is still unknown,” they write. What is known is that viruses closely related to XMRV do cause many different diseases — including cancer — in other warm-blooded animals.

How Is This Relevant To CLL Patients?

Let me be the first to admit most of my comments below are speculative in nature.  But I am also inclined to think there may be more here than meets the eye for CLL patients.   Read on, you can draw your own conclusions.  This is interesting stuff.  There is no way of predicting the directions of future research, but I for one would be delighted if it turns out there is a link between CLL and a viral infection of some sort.  Why, you ask.  Well, if we know what is causing CLL, we will be in a better position to treat it, even prevent it in the first place. 

Two striking examples come to mind, where improved knowledge of the viral drivers lead to better treatments.  HIV / AIDS diagnosis was an immediate death sentence back in the early stages of the AIDS epidemic.  Not so now.  AIDS patients can live long and reasonably healthy lives because of therapy using powerful anti-retroviral drugs  combinations (“cocktails”)  that can control the HIV virus and thereby prolong lives, improve quality of life for patients.

I am sure you have heard of the human pappilomavirus (HPV).  There are many different kinds of pappilomaviruses.  Some do nothing more than cause unsightly warts.  Others cause infection of the mucous membranes, a few of these can progress all the way to full fledged cervical and vaginal cancer.  Discovery of the viral origins of some forms of cervical and vaginal cancer was a breakthrough.  Knowing the culprit(s), it is easier to find ways of fighting it.   For starters, we have learned that the virus is sexually transmitted and therefore safe-sex practices are of potential value in preventing infection.  But even more important, it is possible to develop vaccinations against viral infections.  We are learning how to protect young girls against cervical and vaginal cancer by means of  vaccinations against HPV.  Who knows, in a couple of generations cervival and vaginal cancer deaths caused by HPV may be a thing of the past.

Won’t it be wonderful if someday we learn that there is a specific viral driver for CLL, or even there is a virus that makes existing CLL more aggressive?  Knowing the name and face of the enemy is half the battle.  If there is a viral driver for CLL, we can hope to develop anti-viral drugs with which to control it.  Down the road we can hope to develop vaccines to prevent it.  For all of us in the patient community with children and grandchildren, knowing the familial nature of this cancer and the increased risk of our kids getting CLL, won’t it be wonderful if we are working towards a vaccine that will reduce or eliminate their risk?

Fatigue - a classic “B-Symptom”

Let me line up a few interesting facts that may (or may not) be connected.

  • Deep seated fatigue is often experienced by CLL patients.  It is one of the classic “B-symptoms”.  As you should know by now, most experts agree initiation of therapy for CLL is not driven by blood counts but by start of B-symptoms.  These symptoms are seen as an indication the underlying CLL has reached a stage where it needs to be treated.
  • I used to think the fatigue in CLL was due to anemia.  As CLL advances, other blood counts take a hit, including red blood cell counts.  With fewer red blood cells and not enough hemoglobin, precious oxygen supply to all the cell of the body gets reduced - a classic pattern in  chronic anemia that causes lack of energy and fatigue in otherwise healthy patients. 
  • However, over the years I have heard from dozens of CLL patients whose quality of life took a big hit with mind numbing fatigue - and their red blood cell counts, hemoglobin, hematocrit etc were still pretty much OK! This is anecdotal information, the only kind I have access to.  But I am willing to bet that there is significantly less than 100% connection between low red blood cell parameters and B-symptom fatigue.  What gives?  What is causing the fatigue if it is not just garden variety anemia?  Write and let us know if you fall into this category - fatigue that cannot be explained by anemia alone.
  • CLL patients have poor immune defences against viral infections.  We know our guys are more prone to catch any new viral infection going around in the general public.  We also know that dormant viruses (such as cytomegalovirus, Epstein-Barr virus and Herpes) most of us have in our bodies can use the window of opportunity provided by immune suppression to flare into full fledged infection.
  • The article above suggests some 10 million Americans carry the XMRV virus, and that it is most likely spread by human to human contact routes.  The new research suggests there is good reason to believe it may be the cause of chronic fatigue syndrome in majority of patients afflicted with this disorder.

Interesting Speculation

Please be aware this is not something that has been shown in any formal study. I am intrigued by these possibilities and I am presenting my speculations here for your comments and discussion.

  • What are the chances that at least in a percentage of cases B-symptom fatigue in CLL patients is caused XMRV virus infection, either recently acquired or a trace residue of an old infection the virus reactivated?  If this is the case, can it be treated by appropriate anti-viral therapy?  In other words, are we assuming B-symptom fatigue is an automatic signal of CLL getting aggressive, when it could be nothing more than a viral infection?
  • We know that even healthy people have slight tenderness and swelling of lymph nodes soon after they pick up an infection of some sort - part of the normal process of fighting disease as the body goes into high alert and makes many more of the white blood cells needed to fight the viral hordes. But in CLL patients the overwhelming percentage of white blood cells are cancerous CLL cells. What are the chances  XMRV infection (or reactivation of trace levels of the virus from prior infection) is directly or indirectly implicated in doubling time of CLL counts getting shorter, lymph nodes becoming swollen and tender (more infamous B-symptoms)?
  • There is often a feed-back loop between viruses and the infections they cause, a sort of snowball effect.  For example, infection of immune system T-cells with the HIV virus causes the victim to become even less capable of fighting viral invaders, which in turn makes it easier for the HIV virus to infect more T-cells and so on, in an accelerating spiral. Are we seeing a similar snowball effect, XMRV getting a toe-hold in an immune compromised CLL patient, then the viral infection acting as a driver for making the CLL more aggressive?

Oncoviruses

Cancer causing viruses are not new on the scene.  Oncovirusushave been identified and catalogued for sometime now.  Close to home, several forms of B-cell cancers such as Burkitt’s lymphoma (a type of NHL) as well as Hodgkin’s disease are known to be linked to Epstein-Barr virus (see the table below).

EBV is particularly interesting to me.  As we pointed out in an earlier article (“The Enemy Within“) pathology of Epstein-Barr virus seems to be of  relavance to CLL.  It is estimated that the vast majority of human beings have been infected with the EBV virus at some time in our lives and as a consequence most of us carry trace elements of this virus in our bodies for the rest of our lives.  Recent work at M. D. Anderson showed intriguing connections between prior history of clinical mononucleosis and more aggressive CLL, possibly increasing risk of dangerous Richter’s syndrome.

Let me draw the distinction between having been exposed to EBV at some point in your life and therefore testing positive for it, versus full fledged, clinically diagnosed mononucleosis (“glandular fever” for our Brit members).  There is a big difference between the two.   We did a straw poll a while back.  We asked how many of our members had been diagnosed with mononucleosis as kids.  A surprisingly high percentage of CLL patients have had mono as teenagers, much higher percentage than the general population.  Is this an interesting lead?  Does prior history of massive EBV infection make people more likely to get CLL later in their lives?

An even more out-on-a-limb extrapolation of the data:  a surprisingly large percentage of our members are of Ashkenazi Jewish background.  Mononucleosis is also thought to be more pronounced in this ethnic group.  Is there a link here that should be studied?  If I were to win one of those mega million dollar lottery jackpots, this is the kind of research I would support with my ill gotten wealth.  I suppose I should buy a lottery ticket first, before I start day-dreaming.

As always, I believe the winning strategy in any war is to know as much about the enemy as we can.  If there is a viral driver that is at the root of CLL, either in initiating this frustrating cancer or making it more aggressive, surely this is an area of  research that is of profound interest to our patients.