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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The HUT 78 cell line
In our rapid response “More on the photo”, 25th June we wrote:
"Christopher Noble's pictures raise some interesting questions. Being HIV experts, Christopher Noble and Brian Foley undoubtedly are aware that the H9 cell line, like the MT-1 cell line, originated from patients with adult T4 cell leukaemia. This disease is said to be caused by HTLV-1. In fact, as far back as 1983 Gallo showed that the H9 cell line is infected with HTLV-1. The H9 cell line is the cell line most extensively used in HIV research. The questions then are (i) why have Christopher Noble and Brian Foley never mentioned that in the H9 cell line there is a "real soup" of retroviruses and (ii) how do Christopher Noble and Brian Foley distinguish between what is "HIV" and what is HTLV-1 in this cell line?”
Christopher Noble’s response (30th June) was: "It is hard to be aware that H9 originated from a patient with adult T4 cell leukaemia because it in fact originated from a patient with Sezary Syndrome. (1)".
The first sentence in the abstract of Christopher Noble's reference (1) reads: "Efforts at the National Cancer Institute to generated continuous in vitro cultures from patients with mycosis fungoides and the Sezary syndrome, neoplasms with a mature T-helper [T4] phenotype, led to the establishment of two cell lines, HUT78 [H9] and HUT102". In his article "The First Human Retrovirus", published in Scientific American, 19861 Gallo wrote: "There was, however, some confusion about the disease HTLV-1 was associated with. This was bound to be the case, since the origin of T-cell leukaemias was not well understood, and so clinicians had been forced to rely on symptoms to categorise the forms of the disease. The patients from whom we first isolated HTLV-1 had malignancies of mature T4 cells accompanied by skin abnormalities, which result from infiltration of the skin by malignant blood cells. Such a clinical picture has been called mycosis fungoides or Sezary T-cell leukaemia".
Christopher Noble wrote: "Despite the claims of the Perth Group neither Gallo nor Montagnier have ever claimed that H9 is infected with HTLV-1. What Gallo says is quite different. "Another cell line, HUT 78, of a mature T cell that expresses no HTLV antigens or viral particles contained HTLV proviral sequences". Gallo does not say that HUT78 is infected with HTLV-1. Nobody except the Perth Group and their followers has ever made this claim".
Christopher Noble knows that a cell infected with a retrovirus, in order to express retrovirus particles and antigens, must be activated/stimulated, that is the cell must be treated with oxidising agents.2 Neither in the 1983 paper nor in his 1984 papers where he reported the H9 clone to be HTLV negative is there any mention that the HUT78 (H9) cells were stimulated. Would Christopher Noble consider the significant number of cells in the AIDS patients which have "HIV" proviral sequences but which do not express viral particles and antigens, as being '"HIV-1 negative"? Would he consider AIDS patients with non-detectable "viral load" as being cured of "HIV"?
NOTE: The non "HIV" infected HUT78 (H9) cell line has been reported to express virus like buds and cell free particles.3
Christopher Noble wrote: "As Montagnier never claimed that the H9 cell line is a "real soup" there is no reason for any of us to mention this "fact"."
Montagnier was aware that the HUT78 (H9) cell line originated from a patient having a "neoplasm with a mature T-helper phenotype", and that it "contained HTLV proviral sequences".
In his 1997 Djamel Tahi interview Montagnier stated:
DT: "With what did you culture the lymphocytes of your patient? With the H9 cell line"?
LM: "No, because it didn't work at all with the H9. We used a lot of cell lines and the only one which could produce it was the Tambon lymphocytes"
DT: "But using these kinds of elements it is possible to introduce other things capable of inducing an RT and proteins, etc"
LM: "Agreed completely. That's why finally we were not very ardent about using immortal cell lines. To cultivate the virus en masse – OK. But not to characterise it, because we knew we were going to bring in other things. There are MT cell lines which have been found by the Japanese (MT2, MT4) which replicate HIV very well and which at the same time are transformed by HTLV. So, you have a mix of HIV and HTLV. It is a real soup"(emphasis ours).
1. Gallo RC. The First Human Retrovirus. Sci Am 1986;255:78-88.
2. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Oxidative stress, HIV and AIDS. Res Immunol 1992;143:145-8.
3. Dourmashkin RR, Bucher D, Oxford JS. Small virus-like particles bud from the cell membranes of normal as well as HIV-infected human lymphoid cells. J Med Virol 1993;39:229-32.
Competing interests: None declared