VIRUSMYTH HOMEPAGE
RETROVIRUSES... REVISITED
Letter to Science & Nature
By Etienne de Harven & Gordon Stewart
February 1999
In February 1999 the following letter was submitted for publication to Science. The letter was rejected. An almost identical letter was submitted in May to Nature, which has been equally rejected.
In 1970 molecular biology made a U-turn when it was found that DNA could be synthesised from an RNA template by the action of a hitherto unknown enzyme which was given the name reverse transcriptase (RT). This enzymatic activity was recognised simultaneously in preparations regarded as purified Rauscher-murine leukemia viruses by D. Baltimore (1 ), and as purified Rous sarcoma virus by H. Temin and S. Mizutani (2). These observations provided a possible new understanding of the oncogenic properties of RNA tumor viruses, which were promptly renamed as "retroviruses". They gave an enduring impetus to the study of these viruses as hypothetical causes of some human cancers and leukemias, and led to the award of a Nobel Prize. But they also raised some serious questions which are still unanswered.
The viral samples used by Temin and Baltimore were obtained, as far as is known, from bands sedimenting in sucrose gradients at a density of 1.16 gm/ml. These samples were regarded as “pure" virus, and the RT activity was, therefore, interpreted as that of a viral enzyme. However, electron microscopy was apparently not used by the authors to control the level of purity of the viral samples and the absence of contamination by cellular debris.
Since then it was learned that material sedimenting in sucrose at the density of 1. 1 6 gm/ml is very heterogenous and contains large amounts of cell debris and microvesicles, as recently confirmed by two different groups of investigators (3, 4). Moreover, it was established that reverse transcriptase activity is found commonly in most cells, as already indicated by Scolnick et al. in 1971 (5) and reviewed by Varmus (6) in 1988. Consequently, the presence of cell debris may account for reverse transcrip-tase activity.
In view of these facts, we believe it becomes extremely urgent to reappraise the currently accepted assumption that reverse transcriptase activity can be used as a “marker” in surrogate tests for the presence of “retroviruses” such as the so-called Human Immunodeficiency Virus (HIV).
Etienne de Harven,
Emeritus Professor of Pathology, University of Toronto, Canada
Gordon Stewart
Emeritus Professor of Public Health, University of Glasgow, UK
References
- D. Baltimore, Nature 226, 1209 (1970).
- H. M. Temin and S. Mizutani, Nature 226, 1211 (1970).
- P. Gluschankof et al., Virology 230, 125 (1997).
- J. W. Bess et al., Virology 230, 134 (1997).
- E.M. Scolnick et al., Nature 229, 318-321. (1971)
- H. Varmus, Sci. Am. 257, 48 (1987).
VIRUSMYTH HOMEPAGE