I will be delighted to serve on the subcommittee to deal with the nomenclature of human retroviruses. For the purpose of
organizing relevant portions of the forthcoming supplement to the Cold Spring Harbor RNA Tumor Virus book, I have spent considerable
time grappling with the genome structure and organization of these viruses (and retroviruses generally) and have formed some
opinions on the subject, as stated on the enclosed pages. I offer this only as a starting point for discussion, however.
I presume it will be representative of a major class, but by no means all responses.
With best regards,
John M. Coffin, Ph.D.
First, on the issue of classification (which we are not discussing but must nevertheless be aware of). Nucleotide sequence
information allows the division of virus genomes into some clear groups, within which there is "obvious" sequence
relationship and between which there is usually detectable - but certainly not obvious - relationship. Those groups that
can be well defined at this point include:
1) MLV-related viruses, often called "mammalian C-type", including endogenous and exogenous MLV, FeLV, GaLV, SSV endogenous
viruses of rats, monkeys, and humans and the reticuloendotheliosis viruses of birds.
2) ALV-related viruses "avian C-type" primarily exogenous and endogenous viruses of chickens and pheasants.
3) Mouse mammary tumor viruses.
4) D-type viruses (MPMV and relations) of primates.
5) HTLV-I, II, and BLV and similar primate viruses.
6) The AIDS/LA viruses of humans.
The first of these groups has the largest number of well-characterized members of diverse origins and its properties suggest
a basis for distinction. In addition to obvious sequence homology, numerous other shared features of this group exist including
virion morphology, genome size, size of the LTR and its subregions, tRNA primer (except perhaps some endogenous relatives
of questionable functionality), divalent ion requirement for reverse transcriptase, size and composition of gag and pol precursors,
and others. This collection of characteristics, taken together, might serve as a basis for defining a "species" (or
perhaps "genus") of viruses. It seems now apparent that the taxonomic value of any of these traits individually is
rather limited. Furthermore, several traits seem to be unsuitable as classification criteria except at the most subtle level,
including presence and type of onc genes, species of isolation, endogenous vs. exogenous lifestyle, tissue specificity of
replication, and lytic vs. benign vs. transforming response.
The above discussion assumes that it is desirable for taxonomy to strive to follow evolutionary relationships as revealed
through sequence homology. As far as I can tell, it is essential to do so, for to knowingly do otherwise is to create a system
based on arbitrarily chosen characters - useful as a field guide to known viruses, perhaps, but not capable of providing clear
guidance for the placement of new isolates, quite possibly with novel combinations of characters. The above grouping must
therefore be imbedded within the taxonomic scheme chosen.
Given all of this, it seems impossible to justify treating the T-cell lymphoma viruses and the AIDS-associated viruses as
a single group. The differences far outweigh the similarities. There is only a very small amount of sequence homology (whether
it is more or less than either virus with RSV is immaterial); the LTR organization is different as is the tRNA primer, the
relationship between gag and po1, the presence of an open reading frame 5' (or 3') of env the structure of the env
gene. Apparently common features such as species or cell specificity, transactivation, presence of additional open reading
frames beyond gag, po1, and env, are not obviously rooted in common structural (or even mechanistic) features. For example,
BLV is neither human nor T-lymphotropic, but clearly belongs with HTLV-I and II where HTLV-III, which is both, probably does
Non-scientific issues aside, it seems to me it would be highly desirable to name the AIDS viruses in a way that does not imply
close relationships that are not there. While names for viruses must be trivial and therefore it doesn't matter what
one calls a virus so long as there is general agreement, the use of names that sound like unrelated viruses can only cause
unnecessary confusion. I can visualize myself lecturing to medical students (for example) on human retroviruses and having
to explain that while HTLV-I and II (and maybe IV and V by that time) are quite similar in structure and strategy, HTLV-III
is quite different. I doubt that it will be possible to get the point across very easily. It would be far easier to present
them under different names and then explain what the similarities are. The situation, of course, will be even worse if the
reported relationship with lentiviruses stands up to sequence analysis.
Thus, while there should be a group designation for the AIDS-related viruses, I think it would be most unwise to make it anything
resembling HTLV. Perhaps "AIDS-lymphadenopathy-associated virus" (ALAV) or something similar would do. The retention
of the names HTLV-III, LAV, ARV, etc. for individual isolates is likewise undesirable, but most likely unavoidable.