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Relationships Between Human T-Lymphotropic Virus Type II (HTLV-2) and  Human Lymphotropic Herpesviruses
in Chronic Fatigue Syndrome

Research Proposal

Konstance K. Knox, Ph.D. and Donald R. Carrigan, Ph.D.
Institute for Viral Pathogenesis
10437 Innovation Drive
Suite 417
Milwaukee, Wisconsin 53226

Project funded by The National CFIDS Foundation, Inc.; Needham, Massachusetts


In 1991 Dr. Elaine DeFreitas and coworkers the Wistar Institute in Philadelphia reported that at least a portion of the genome of a retrovirus [human T lymphotropic virus two (HTLV-2)] was present in the white blood cells of many patients with chronic fatigue syndrome. The viral DNA sequences were present in 72% and 83% of children and adults with CFS, respectively. DNA samples from healthy people were negative for the viral DNA sequences.

Since 1991 there have been five additional published reports of studies of HTLV-2 in CFS. These papers were identified by a search of the National Library of Medicine in Washington. Of these reports, one was a non-peer reviewed survey published in the Morbidity Mortality Weekly Report of the Centers for Disease Control and Prevention (CDC). Although it is not stated, it is implied that one of the laboratories involved in this study was that of Dr. DeFreitas. In the study, no differences were found between CFS patients and healthy people with respect to the detection of HTLV-2 DNA sequences in white blood cell DNA (approximately 60% of both groups were positive for viral DNA sequences). The main strength of this study was that the samples were analyzed in blinded fashion, i.e. the people running the tests did not know whether the samples came from CFS patients or healthy controls. Weaknesses of this report include:

  • failure to use the exact procedures as those used by Dr. DeFreitas
  • the laboratories involved in the study are not identified
  • no technical details concerning the procedures used are provided
  • the patients are not clinically described except that they met the 1988 CDC criteria for CFS.

Another of these five reports is that of Dr. J Gow and coworkers from laboratories in Scotland and Germany Using the same procedures as those in the original work by Dr. DeFreitas et al. as well another, related procedure, no differences were observed between CFS patients and control subjects (100% of both groups of subjects were positive for HTLV-2 DNA sequences). Weaknesses of this study include:

  • the use of a European case definition for CFS (6) which differed substantially from that used in the United States
  • failure to use the exact procedures used by Dr. DeFreitas

The remaining three publications were from the same group of investigators at the CDC. These studies, which utilized procedures similar to those used by Dr. DeFreitas, failed to detect HTLV-2 DNA sequences in either CFS patients or healthy people. This finding stands in stark contrast to the observations of Gow as described above. Strengths of these three studies included:

  • they were for the most part performed in a blinded fashion
  • they attempted to correlate their findings with a variety of factors
  • they sought a variety of animal retroviruses in addition to HTLV-2.

Weaknesses of these three studies included:

  • failure to follow the same experimental procedures as those used by Dr. DeFreitas
  • the results of these studies are somewhat misleading in that the data reported in all three papers apparently were obtained from a single experiment involving 21 CFS patients and matched controls. No reference is made to this fact in any of the three publications.

In conclusion, the results reported by Dr. DeFreitas and her colleagues at the Wistar Institute have not been reproduced by other, independent laboratories. However, these subsequent investigations differed substantially from the original studies in a number of ways, including:

  • clinical definition of the CFS patients studied
  • uniform failure to use the same procedures as those used by Dr. DeFreita

Specific Research Proposal

The goals of the proposed studies are:

  • to use contemporary molecular diagnostic techniques in an attempt to confirm the findings of Dr. DeFreitas with respect to the presence of HTLV-2 DNA sequences in the white blood cells of patients with CFS
  • To correlate the presence of HTLV-2 DNA sequences with the presence of active infections with human herpesvirus six (HHV-6) or Epstein-Barr virus (EBV), two viruses that have been implicated in CFS