NAMING THE AIDS VIRUS
Harold E. Varmus, M.D.

Departments of Microbiology and Immunology and
Biochemistry and Biophysics

School of Medicine, University of California

San Francisco, California 94143

(Tel. 415-476-2824)
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Between April 1983 and AT he 1984 ae research groups in three locales
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three thousand miles apa fruses advanc as candidates for the

causative agent of the acquired immurty efficiency syndrome aie (1-3).

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Although these viruses were each called different names by the ¢#euge that

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reported them, the many isolates
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agemes within asdexge and well-studied class known as
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retroviruses (4). By the end of 1984, it was apparent that both the

scientific community and the public would be better served by a single name

for the causative agent of AIDS, but it was much less clear what that name
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Since March, 1985, I have chaired a committee composed of thirteen well-
known retrovirologists from four countries/ attempting to find a single

acceptable name for this important new group of human retroviruses, whtle-~

 

This duty has fallen to me

because I chair a standing subcommittee, known as the Retrovirus Study Group,

which is empowered to rule on matters of ®iral nomenclature and classification

under the aegis of a larger group known as the International Committee on the
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Taxonomy of Viruses. We were -eabkksd-to action on this occasion wherrtekegan
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—sempmeivs. calls and letters from virologists close to and distant from the

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experimental activity, asking fee=seme neutral group 3% offer a solution to

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what had become an intractably confusing « and at time, con fiténtious issue.

. Liiaphee, are sporadic,

often pedantic, and of a@ concern to the general public, albeit useful to

 
    

The normal workings of «pm “at ght

 

those who must work with and talk about viruses. In the case of the AIDS

virus, however, our activities have attracted extraordinary attention and

curiosity.
Why has there been so much interest in the resolution of a problem which
would appear to have no immediate relevance to the serious issues in the AIDS
crisis---controlling the spread of this virus and treating its victims?

Some perceive, wrongly in my view, that our final recommendation will form a
verdict upon contested issues of priority of discovery, issues that could
influence patent rights, the awarding of major prizes, patriotic sentiments,
and financial gain. Others have seen our deliberations as a battle between
Robert Gallo and Luc Montagnier, both members of the Committee and leaders of
the two most highly publicized groups to isolate AIDS retroviruses; this is
certainly an oversimplified view of the proceedings. For many who follow the
AIDS problem closely as experimental scientists, health care workers, or
public-spirited citizens, the issue may simply be one of having a single,
convenient, and generally accepted name for the virus that causes the disease.
And for an appreciable number of scientists, the task has a higher purpose,
eloquently expressed by Stephen Jay Gould (F):

",,.taxonomies are not neutral hatracks for the pristine facts of nature.
They are theories that create and reflect the deep structure of science and
human culture. A taxonomy is not just a ploy for convenient arrangement, but
a hypothetical statement about the nature of things."

In fact, the issue before us has not been taxonomy per se, but
nomenclature; we have attempted to settle upon what is usually called the
common or species name for a virus or collection of very similar viruses.
Since such names are in daily use by the working virologist, much ink and some
blood has been spilled over them; the forces that influence decisions about
them are as various as the forces that influence the naming of a baby, a book,

a bridge, or a city.
Scientific principles, political realities, aesthetics, convention, and
justice must all be served in the process of finding the species name for a
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virus. Many questions had to be considered for each suggestion dGeingthe
preerattéd procese: Is the proposed name consistent with scientific facts and

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with~Hee tentative classification? Is there anything objectionable about the
name that would prevent its being used? Have those credited with discovery
been accorded their rights to contribute to the process of naming? Does the
name distinguish the virus from those it does not resemble? Is the name
readily remembered? Is the name likely to create confusion in the future if
and when other viruses are isolated? Does the name conform to existing
conventions for naming viruses of this general type?

Before discussing specific names proposed for the AIDS virus, I must
briefly introduce a debate that has been raging among namers of viruses for
the past few years. The definition of an animal species is based upon the
ability to mate productively; membership in a species is granted to those
animals that can interbreed with other members. Since viruses do not have sex
in the conventional sense, grouping of viruses that are so closely related as

In ee ast

to be accorded a common name was often based upon any conveniently measured
biological or biochemical property---such as virus shape, or immune reactivity
or presence of a certain enzyme in the virus particle.

With the application of new genetic and molecular techniques to the study
of viruses, however, it has become possible to define virus groups in a
fashion analogous to that used for animals, in a way that is likely to come
closer to establishing true evolutionary relationships among viruses F). In
this new view, it is possible to assess which viruses are so closely related

genetically that they could exchange genes without loss of viability, in the

manner of animals that can generate viable offspring by the intermingling of
their genes. Such viruses properly constitute a species and can usually be
clearly distinguished from those that are genetically disparate, regardless of
other similarities.

In the context of the AIDS viruses, for example, it was apparent by the
time our deliberations began that the available isolates were sufficiently
closely related to be considered members of the same virus species. The
questions, in large part, were whether and how they should be distinguished 7

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from human retroviruses that appeared to belong to other species Nye

What. names did we have to consider? Several names were already in use.
Most prominent among these were lymphadenopathy virus (LAV), human T cell
lymphotropic virus-III (HTLV-III), AIDS-associated retrovirus (ARV), two
hybrid names (HTLV-III/LAV and LAV/HTLV-III), and a name often used by the

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press (the AIDS virus). In short order, many more names, about fifty «daen ,

all permutations See CECE were suggested by committee members,
consultants, and other correspondants.

How could we decide among these many candidates? When confronted by
confusion, it is sometimes useful to sa@ke-e-cansesmativespest-tionymends
consider what has worked well in the past. Retroviruses form a large group
of agents united by a distinctive property: they carry their genes in the
form of ribonucleic acid (RNA) and convert them to deoxyribonucleic acid
(DNA) after infection, reversing the usual flow of information in nature from
DNA to RNA. Poyeeny Pspite this unifying feature, retroviruses are also
manifestly diverse: they are found in many different animal hosts, cause

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several different types of disease, and frequently appear to be only é
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marginally related when the substance of their genes is carefully examined (4.

This complexity has generated a need to group isolates in a rational manner

that emphasizes biological boundaries.
Traditional retroviral nomenclature has worked well in this regard. The
convention has been to name viruses according to the host species of origin
and the prominent pathology associated with the prototypic isolate of a single
type; two examples of such names are feline leukemia virus and ‘house mammary
tumor virus .* Individual isolates belonging to a single species are further
distinguished by prefixes or suffixes (numbers, letters, or [in earlier times]

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names of discoverers), as in Rauscher murine leukemia virus or human T cell

leukemia virus-2.\'

Many of us have favored staying close to these traditional rules, but
there were obviously other considerations as well. In particular, the rights
of discoverers needed to be respected, but it was clear from outset that we
could not reach a consensus about eminent domain. It thus seemed prudent to
set as an objective the best possible name, to include all claimants in the
proceedings, and to hope that all parties would find some solution acceptable.

If we were to adopt a traditional name for the AIDS retrovirus, we needed

to consider a particularly troubling issuegpeWhe ther names that included the
term "AIDS", such as human AIDS virus or human AIDS - lymphadenopathy virus,"
were likely to be psychologically damaging in the clinicesein view of the
lethality of the disease and the social stigmas attached to the prevalent
routes of virus transmission. To explore this issue, we asked over fifty
clinicians who had worked with AIDS patients for their opinions. The large
number who responded showed geniune and intelligent interest in the choice of
names, but they were almost exactly divided over the issue of whether to
exclude "AIDS" from the name. Some took the position that patients would
soon be Mar as fearful ert term that denoted the agent of AIDS as Hh
PiEte about a term that was explicit, a phenomenon our committee HEH

referred to as "the evanescence of euphemism." Others felt strongly that it
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was easier to explain the difference between infection by the virus and the
disease induced in a minority of infected people, if the virus had a name with
less perjorative potential.

There was general agreement among our membership that the latter view
should prevail, if only because strict adherence to simplicity and convention
was not important enough to outweigh the misfortune of even a rare patient
suffering needlessly from the report of an antibody test. Moreover, it was
possible to consider use of terms that denote the principal pathological
consequences of infection---e.g. "immunodeficiency" or “immunosuppression"---
thereby avoiding the name of the disease, yet conforming to standard

nomenclature.

The many names suggested for the AIDS virus raised other taxonomic
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possibilities. Some encouraged the use of host cell aftini thee, as a basis for

A fname, a view already in wide circulation through the use of "human T cell

lymphotropic virus" and endorsed by other suggestions, such as "human T4
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virus" tompage the cellular receptor that determines whether the virus can
enter a cell. (This approach is discussed more fully below.) Another
possibility was raised by experimental evidence linking the AIDS virus with a
handful of animal retroviruses that produce disease slowly and are hence known
as lentiviruses, one of the three large subgroups of retroviruses (7 ).
However, enthusiasm for "human lentivirus-1" was dampened by the still weakly
defined characteristics of this class and by the inappropriateness of using as
a species name a name normally applied to a collection of diverse virus
species. Others suggested defusing the political, clinical, and genetic
issues through the use of a sequential numbering system, in which the AIDS

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virus Yould become human retrovirus-3. However, colorless names of this type

can be difficult to connect with the right virus, especially when the list
becomes lengthy; the approach does not respect the genetic basis of virus
speciation, since human retroviruses from different species would have names
that differ only by number; and attempts to impose similar systems upon other
virus groups, such as human herpesviruses, have not always been successful.

From a pragmatic perspective, we had to consider the already widespread
use of the term human T cell lymphotropic virus-III (HTLV-III) and to ask
whether it was too firmly entrenched to be displaced by a new name. This

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tactical qucssion, however, a, closely. linked /te- the the6retical issue of how
modern virologists view the world, and how they recreate it for their students
through the choice of names, because the term HTLV-III presents a direct
challenge to the genetic basis of virus speciation.

Proponents of HTLV-III wish to group it with HTLV-I and -II---viruses
orginally called human T cell leukemia viruses, but proposed to be renamed as
T cell lymphotropic viruses---based upon a long list of common features (& ).
However, the most prominent of these similarities appear superficial and
deceptive when closely examined. Thus, though both virus types have strong
predilections for infecting the T4 subset of thymus-derived lymphocytes, the
mechanisms determining that preference are fundamentally different for the
leukemia viruses and the AIDS virus; the two groups of viruses use different
host cell receptors to gain entry into the lymphocytes, and, as a consequence,
they also differ with regard to other cell types they can infect. Second,
though the leukemia and AIDS viruses are pathogenic for man, they cause
dramatically different types of pathology, resulting on the one hand from

inappropriate proliferation of infected cells and on the other from toxicity

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and death of infected cells. Third, despite several similarities in sizeof
the proteins found in leukemia and AIDS virus particles, the sequences of the

building blocks (amino acids) of these proteins are now known to be as
different as the sequences for any two ostensibly unrelated retroviruses,
Finally, though both types of viruses exhibit relatively unusual mechanisms
for improving the efficiency with which they produce the proteins encoded by
their genes, on close inspection the mechanisms appear to be largely unrelated
Fy.

The explanation of these fundamental differences is immediately apparent
when the viral chromosomes (known as genomes) are compart? Though the
genomes of the AIDS and leukemia viruses share features that are common to all

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retroviruses fam -eeatfistets --- symmetrical units tha® govern gene expression
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and the basic layout of genes for the proteins found in virus particles---
wherever they can differ, they do. Most obviously, the order of the
components of the genome differs, so that the sequence of nucleotides is no
more similar for these two groups than for any two members of the diverse
family of retroviruses. But important subtleties are also evident: the manner

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in which the Jgones are juxtaposed assigns the viruses to different classes,

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and the position and nature of (genes ether. than those.that—encode proteinsndor

the wisweeperrtties are entirely unrelated.

If an evolutionary tree is established for retroviruses by comparing the
order of amino acids in the protein most characteristic of retroviruses, the
enzyme that converts RNA to DNA, it is apparent that the AIDS virus is most
closely related to the sheep lentivirus, called visna, whereas the human T
cell leukemia viruses are in another limb of the tree, more closely related to
other oncogenic viruses, leukemia and sarcoma viruses of various animals,
particularly the bovine leukemia virus A). To those who believe in the
application of genetic principles to virus nomenclature, it is apparent that a
superficial resemblance in host cell tropism should not be used to impose a
species designation upon viruses that are highly divergent according to + fr %-

rigorous criteria.
Through a series of memoranda and polls that Sought a consensus on these

kxheary wes view? sland fvelusiud, * pth e Aye thank ,

issues, we*narrowed the choices to a few ‘identified a name
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approved by a resounding majority, but not by acclamation. (That name and the
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letter officially proposing it to the scientific community g# presented in the
Postscript.) The issue that remains is a practical one: can we bring this
name into common use? Or will we simply have added an academic suggestion,
albeit one enshrined in the official logs of an international agency, to the
list of names already used?

Colleagues sometimes ask why we should care about this issue, with
convictions that go beyond the usual manifestations of good scientific
citizenship. During our deliberations, at least two components of our
commitment have emerged. As proponents of the disciplines of virology and
genetics, we want them to operate in a way that seems to us and to students we
train scientifically sound. Moreover, we would like the public view of our
science to be one that acknowledges the reality of disagreement, but one that
also admires the willingness of intellectual combattants to compromise for
advancement of our shared purpose. A prolonged battle over the issue of a
name for the AIDS virus is more than trivial, because it may come---some might
say it has come---to symbolize certain excesses of character for which
scientists are often criticized. This seems particularly unfortunate in view
of the truly extraordinary accomplishments that have been made in a very short
time by the laboratories involved in the debate. A generally accepted
recommendation for a name for this virus could help restore to the public
whatever faith has been been lost through this issue during the confusion of
the past two years.

i

Postscript

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During the first week of May, 1986, the following letter, from our
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Subcommittee appeared in the journals Nat te And Science.’ Two members of our

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group, Myron Essex and Robert Gallo, declined to sign the agreement.

To the Editor:

The undersigned are members of a subcommittee empowered by the International
Committee on the Taxonomy of Viruses to propose an appropriate name for the
retrovirus isolates recently implicated as the causative agents of the
acquired immune deficiency syndrome (AIDS). Adoption of an internationally-
acceptable name for this group of viruses has become an important issue
because of the widespread interest in AIDS and its origins and because of the
multiplicity of names currently in use. Thus the several isolates of what are
now evidently closely related members of the same virus group have been called
lymphadenopathy associated virus (LAV), human T cell lymphotropic virus type
III (HTLV-III), immunodeficiency associated virus (IDAV), and AIDS-associated
retrovirus (ARV). At present, two compound names (HTLV-III/LAV and LAV/HTLV-
III) are also used in scientific publications, and the colloquial name, the

AIDS virus, is often used by the press.

Ub te are writing to propose that the AIDS retroviruses be officially designated

as the human immunodeficiency viruses, to be known in abbreviated form as HIV.

We have considered several issues that bear upon this proposal. (i) The name
conforms to common nomenclature for retroviruses, beginning with the host
species ("human"), ending with "virus," and containing a word that denotes a

major (though not the only) pathogenetic property of the prototypic members of
the group ("immunodeficiency"). ("Feline leukemia virus" and “mouse mammary
tumor virus" are two well-known examples of such names for retrovirus
species.) (ii) Though the name clearly connects the viruses to the disease
with which the virus group is associated, it does not incorporate the term
"AIDS", which many clinicians urged us to avoid. (iii) The name is readily
distinguished from all existing names for this group of viruses and has been
chosen without regard to priority of discovery. (iv) The name is sufficiently
distinct from the names of other retroviruses to imply an independent virus
species, a group of isolates that can presumably exchange genetic information
readily with each other but not with members of other known retrovirus
species. These other species include the human T cell leukemia viruses (e.g.,
HTLV-1 and -2), which will continue to be named according to a convention
adopted by several leading investigators in September, 1983. (Though roman
numerals are often used to indicate the type of HTLV, arabic numbers were
originally prescribed in the agreement and are thus used here.) (v)
Retroviruses isolated from subhuman primates and found to be genetically
related and biologically similar to HIV's should be designated as
immunodeficiency viruses of the appropriate host species (e.g., simian
immunodeficiency virus [SIV] or African green monkey immunodeficiency virus
[AGMIV]). (vi) Because HIV isolates are numerous and display considerable
genetic heterogeneity, particularly in the env gene, it will be necessary for
each laboratory to assign subspecies designations to their isolates. We
recommend that each laboratory adopt a code with geographically informative
letters and sequential numbers to identify their isolates (e.g., the 42nd
isolate at the University of Chicago could be described as HIV [CHI-42]).
Initially, the existing, well-characterized isolates, such as LAV-1, HTLV-

IIIB, or ARV-2, should be identified as such in publications to ease the

(&
transition to a unified nomenclature. (vii) Any future isolates of human
retroviruses with clear but limited relationship to isolates of HIV (e.g.,
more than 20% but less than 50% nucleic acid sequence identity) should not be
called HIV unless there are compelling biological and structural similarities

to existing members of the group.

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‘We hope that this proposal will be adopted rapidly by the research community

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working with the viruses.

John Coffin

Tufts University, Medford, MA

Ashley Haase

University of Minnesota, Minneapolis, MN

Jay A. Levy

University of California, San Francisco, CA

Luc Montagnier

Pasteur Institute, Paris, France

Stephen Oroszlan

Frederick Cancer Research Center, Frederick, MD

Natalie Teich

Imperial Cancer Research Fund, London, England
Howard Temin

University of Wisconsin, Madison, WI

Kumao Toyoshima

University of Tokyo, Tokyo, Japan

Harold Varmus, Chairman

University of California, San Francisco, CA

Peter Vogt

University of Southern California, Los Angeles, CA

Robin Weiss

Institute of Cancer Research, Chester Beatty Laboratories, London, England