HHV-6 has long been suspected as one trigger for CFS. HHV-6 reactivation in transplant patients can cause symptoms similar to CFS, including fatigue, cognitive dysfunction and autonomic dysfunction (Zerr 2012). Direct evidence of persistent central nervous system (CNS) infection is difficult to obtain, however, with current standard laboratory tests, as HHV-6 can persist in the CNS long after it has disappeared from the blood stream.
Diagnosis and Antiviral Treatment in Patients with CFS
Elevated antibody titers can only suggest—not prove—that the virus is active. Short of a tissue biopsy, it may be impossible to find direct evidence of chronic HHV-6 infection. Therefore, physicians who suspect active virus, in a chronic case, must usually treat based on clinical judgment of the symptoms, using elevated antibodies as one of several diagnostic “clues.” Infectious disease specialist Jose Montoya, MD, from Stanford University has published data from an open label trial of 61 CFS patients with elevated viral antibody titers who were treated with long term antiviral therapy (Watt 2012). Out of 61 patients treated with valganciclovir (Valcyte), 81% experienced a significant improvement in cognitive functioning and 52% were categorized as responders. Antibody titers were considered elevated if patients had HHV-6 IgG>1:320, EBV EA >1:160 and EBV VCA > 1:640 (Quest/Focus Diagnostics). Dr. Montoya’s study also found that patients with extended treatment (6 months or more) were more likely to respond. Martin Lerner, MD, has also treated 142 CFS patients with elevated antibodies to HHV-6, EBV or CMV with antivirals, finding that 75% improved significantly and continue to improve for 2-3 years while on antiviral treatment (Lerner 2010). However, in this study, those with evidence of other co-infections were less likely to improve.
CFS & CIHHV-6
CFS patients who test positive for HHV-6 on a plasma PCR DNA test should have a follow-up quantitative whole blood test to rule out chromosomally integrated HHV-6 or CIHHV-6. Patients with ciHHV-6 will always test positive on a PCR test because they inherit HHV-6 genomes integrated into the chromosome of every cell. Although this inherited condition affects less than 1% of the general population, the condition appears to be overly represented in patients with CNS dysfunction. Some have theorized that ciHHV-6 patients may be unable to mount a proper immune defense against community acquired strains of HHV-6, and thus develop CNS symptoms that resemble CFS (Montoya 2012, Pantry 2013, in press).
Infecting the brain via the Olfactory Nerve, Limbic Encephalitis
HHV-6 can travel to the brain through the nose, and is also the dominant variant found in the sensory ganglia (Hufner 2007). Rabies and HSV-1 are travel through the nose to cause encephalitis. Like HHV-6, measles and HSV-1 tend to affect the limbic system as well as the hippocampus (Harberts 2011). There have been a number of abnormalities found in both CFS and GWI patients in the hippocampus: reduced concentration of N-acetylaspartate, (Brooks 2000), hippocampal atrophy and 5-HT1A receptor binding in the hippocampus (Cleare 2005).
CFS & HHV-6A
Although HHV-6B reactivates in 97% of transplant patients and will multiply in the saliva in response to ordinary stress or high workload, HHV-6A is the virus most often associated with CFS. It is also the dominant variant found in the dorsal root. Another interesting correlation between HHV-6A and patients with CFS is that a recent study in Europe found that 82% of fine needle biopsy tissue samples from patients with Hashimoto’s thyroiditis were positive for both HHV-6A DNA and messenger RNA, proving that these were active infections (Caselli 2012). By contrast, only 10% of control tissues from patients with thyroid cysts were positive for HHV-6, but none of these controls were found to have active HHV-6 infection.
A Swedish study done in 2001 found that 40% of 219 CFS patients had chronic lymphocytic thyroiditis, as determined by fine needle thyroid biopsies (Wikland 2001), and only half of these patients had abnormal thyroid levels. By this logic, if 40% of CFS patients suffer from subacute thyroid disease, and 82% of it is caused by HHV-6A, then as many of 1/3 of all CFS patients could be suffering from active HHV-6A infection of the thyroid tissue. Although it has not been documented, it has been reported frequently by CFS physiciasn that most patients have a history of thyroid disease.
HHV-6 Infection of the Sensory Ganglia
HHV-6 is well known for invading the hippocampus and other parts of the limbic system, and also establishes residence in the human sensory ganglia (particularly HHV-6A) along with other neurotropic herpesviruses including HSV-1 and VZV (Hufner 2007). Michael VanElzakker, a researcher affiliated with the Tufts University PTSD neuroimaging laboratory as well as the Massachusetts General Hospital Psychiatric Neuroscience division, has published a novel hypothesis on the possible etiology of Chronic Fatigue Syndrome (CFS) (VanElzakker 2013). For years, CFS researchers have been looking in plasma and blood cells for a pathogenic agent that causes the myriad of symptoms experienced by patients with the condition. However, according to VanElzakker, they may have been looking in the wrong place (plasma) and need to search instead in the tissues of the peripheral and central nervous system. During infection, the sensory vagus nerve sends a signal to the brain to initiate “sickness behavior,” an involuntary response characterized by fatigue, fever, myalgia, depression, and other symptoms that are often observed in patients with CFS. However, VanElzakker proposes that when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria, these symptoms would be exaggerated. He notes that many of the symptoms of sickness behavior (such as fatigue, sleep changes, myalgia, cognitive impairment, depression and zinc depletion) are also mediated by proinflammatory cytokines and observed in CFS. Although VanElzakker proposes that any neutoropic virus or bacteria could trigger CFS, HHV-6 is at the top of his list.
Key papers: HHV-6 & Chronic Fatigue Syndrome