HHV-8 and KS 18 October 2004
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Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala

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Re: HHV-8 and KS

HHV-8 and KS

In our rapid response: "Semen, nitrites and KS", 17 September, we wrote: "The "HIV" experts ignored our theory and claimed that KS is either a direct or indirect "fascinating manifestation of HIV infection". Twenty years later, all of them including Nicholas Bennett, Christopher Noble and Peter Flegg agree that this is not the case, and categorically state that the cause of KS is HHV-8. In support of our theory we presented theoretical, epidemiological and experimental evidence. We asked Nicholas Bennett, Christopher Noble and Peter Flegg for similar evidence in support of their claim that HHV-8 is the cause of KS. So far they have failed to do so. This means that the requests in our rapid responses, "Requests to Christopher Noble and Nicholas Bennett", 8 September and "A request to Nicholas Bennett, Christopher Noble and Peter Flegg", 31 August remain outstanding."

In his rapid response, "Re: Requests to Christopher Noble and Nicholas Bennett", 10 September, Christopher Noble wrote: "Both Nicholas Bennett and I provided a number of papers that provide extremely strong evidence for the causal role of HHV-8 in Kaposi's Sarcoma".

Christopher Noble gave us one paper which apparently he considers to contain "extremely strong evidence for the causal role of HHV-8 in Kaposi's Sarcoma". The paper by Nickoloff et al entitled: "Etiology and Pathogenesis of Kaposi's Sarcoma" was published in Recent Results in Cancer Research, Vol. 160, page 331-342; 2002.

In his rapid response: "KS and UV", 20 September, Nicholas Bennett wrote: "I have previously supplied information that supports the premise of HHV8 being an oncogenic virus epidemiologically associated with KS. The simplest conclusion (Occam's Razor) being that it is the likely cause. Other factors do not share the same association. The Perth Group say that I have not done so, but I point them in the direction of the many responses here on the BMJ Rapid Responses, in particular one by myself dated 21st August. If the Perth Group choose to ignore them that is their perogative, but they cannot say I did not answer their request. They have clearly read it because it sparked the discussion regarding the carcinogenic properties of water and semen. It contains references that I'm sure will answer most or all of the questions regarding the oncogenicity of HHV8 and epidemiology of KS (if not them directly, then the references within)."

Epidemiological association is not proof for causation. Neither in Christopher Noble's reference nor in any of Nicholas Bennett's references is there any theoretical basis in respect of the claim that HHV-8 is carcinogenic. Nor is there any experimental evidence that HHV-8 is carcinogenic. All the researchers who have tried to induce KS by HHV-8 have reported that at best they could obtain, "cutaneous lesions resembling Kaposi's sarcoma" or "Kaposi's sarcoma-like lesions". However, "dramatic depletion of CD4-positive cells, progressive impairment of the immune response, and Kaposi's sarcoma-like tumours or terminal B- lymphomas", can be induced "by mating BALB/c female mice to C57BL/6 males during 1-year period (7-10 allogenic pregnancies) followed by immunisation with paternal lymphocytes".[1]

In the Nickoloff et al paper in the section subtitled "HHV-8: The Etiological Agent of KS" one reads: "Strong evidence supports the conclusion that HHV-8 is necessary for the development of KS. First, HHV -8 DNA has been detected in virtually all KS lesions…Second, serological studies have found that a majority of KS patients (80-100%) have specific antibodies to HHV-8 antigens, seropositivity rates, while low in normal donors, are dramatically increased in populations at risk for developing KS, such as HIV-positive homosexual males…Finally, seropositivity or detection of the HHV-8 genome DNA in peripheral blood predicts future development of KS".

However:

(i) Nickoloff et al do not give any references in support of their claims;

(ii) According to the titles of two references given by Nicholas Bennett the DNA detected is: "Herpesvirus-like DNA sequences", "Herpesvirus-like DNA";

(iii) The KS cells "are latently infected";[2]

(iv) In his rapid response, "Re: Re: Re: "HIV" and KS", 8 September, answering James Whitehead, Nicholas Bennett wrote: "As his own post says, the [HHV-8] antibody tests are not altogether reliable, perhaps because they have not gone through the stringent testing and development of other more established tests such as those for HIV". (Since the specificity of the "HIV" antibody tests has never been proven, the HHV-8 antibody test can be only as bad as the "HIV" test);

(v) According to Nickoloff et al the "HHV-8 genes", "encode for homologs of cellular proteins". Since, unlike "normal donors", "HIV- positive homosexual males" have high levels of auto-antibodies, gay men will have a positive test even if not infected with HHV-8".

This means that HHV-8 will appear to be "epidemiologically associated with KS", even if the KS patients are not infected with it. Thus, at present no evidence exists that HHV-8 "is the likely cause" much less that it is the definite cause of KS.

If:

(a) "HIV" is the "etiological agent of AIDS";

(b) HHV-8 is "the etiological agent of KS;

(c) It is unclear what role [if any] HIV-1 plays in KS.[2]

We repeat our question: why is KS an AIDS indicator disease?

References

1. Ter-Grigorov VS, Krifuks O, Liubashevsky E, Nyska A, Trainin Z, Toder V. A new transmissible AIDS-like disease in mice induced by alloimmune stimuli. Nat Med 1997;3:37-41.

2. Nickoloff BJ, Foreman KE. Etiology and pathogenesis of Kaposi's sarcoma. Recent Results in Cancer Research 2002;160:332-42.

Competing interests: None declared