Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso
Send response to journal:
Politics vs. Science
Brian Foley’s rapid response “Politics vs. Science” (31 July 2003), he
wrote: “At the same time they [the Perth group] try to claim that HIV
researchers would call viruses with 40% DNA changes “identical”.”
never made such a claim. What
we have been saying is that genomic variations of up to 40% are said to code for
one and the same virus, “HIV-1”.
Foley wrote: “In fact the two viruses referred to with the 40% distance are
HIV-1 M group subtype B and HIV-1 O group virus MVP-5180:…’
is true that a difference of up to 40% exists between HIV-1 M group subtype B
and HIV-1 O group and HIV-1 group N but also within the HIV-1 M group. (1, 2)
Foley wrote: “The HIV-1 M group and O group viruses do indeed look identical
to each other when viewed by electron microscopy.”
would be grateful if Brian Foley would provide us with references containing
electron micrographs from either the 1.16gm/ml band or cultures showing
identical HIV-1 M group and HIV-1 O group viruses.
Foley wrote: “Yet at the same time they pretend that the very same methods of
research, which have lead to extraordinary discoveries about each of the 9 genes
in the HIV-1 genome (Gag, Pol, Env, Vif, Vpr, Vpu, Nef, Tat, Rev) are all to be
sequencing including of the “HIV” genome is important.
However, before you do the sequencing and talk about 9 genes in the
“HIV” genome, you must have proof that the sequences originated from a
unique infectious retroviral particle, HIV.
So we again ask if Brian Foley would provide us with references which
prove that the “HIV” sequences originated from a unique infectious
retroviral particle, HIV. So far
Brian Foley has not responded to this request which has been put forward in
previous rapid responses.
Foley wrote: “They have even cited papers which discuss the rate of evolution
of the human influenza virus, so they should be aware that HIV-1 and HIV-2
evolve at close to the same rate as all other exogenous viruses with RNA
far as evolution and variation of the “HIV” genome versus other viruses such
as influenza A and papilloma, which according to Christopher Noble (Rapid
Responses “The HIV and “infuenza A” virus genomes” 28 July 2003 and
“Re: Comparing HPV and HIV” 31 July 2003) are even more variable than the
“HIV” genome, it is useful to quote from the some of the best experts on the
“HIV” genome including Brian Foley’s colleagues at the Los Alamos National
generates variants at a far greater rate than do other RNA viruses such as
measles, polio and even infuenza.” (3)
contrast, DNA viruses either encode proof-reading enzymes (e.g., herpes and pox
viruses) or are edited by the host replication machinery (e.g., papilloma
viruses). According, the
mutation rates for DNA viruses are 104 - 106 - fold lower
than their RNA counterparts.” (4) (Note
that the papilloma virus is a DNA virus yet according to Christopher Noble the
human papilloma virus' genome is even more variable than the “HIV” genome,
an RNA genome).
has three distantly related groups: (i)
the main group (M), the group of viruses that cause the global pandemic;
(ii) O, a form that is found with a low prevalence in west central Africa
and has also been found in Europe; and
(iii) N, a very rare form found in Africa…
genetic subtypes have a certain arbitrariness in terms of their
definition……For the sake of uniformity in the field and to facilitate
communication, a team of experts recently assembled to update the nomenclature
system. The genetically distinct
subtypes are labelled A-K (with no subtype E or I).
Circulating recombinant forms (CRFs) describe viral genomes that contain
clearly delineated sections derived from different subtypes, that share a common
ancestor, and that are the basis of multiple infections.
CRFs are thus epidemic strains, which, like subtypes, are of global
importance. There are currently 11
defined CRFs, and more are in the pipeline.
Some of the CRFs infect great numbers of people……Several new isolated
examples of strains that are not clearly related to any defined subtype, and
that are not obviously recombinants, have also been found.
The subtypes themselves are growing ever more diverse with time.
The combination of these factors results in a massive pressure on the
current nomenclature system, and probably will eventually result in a breakdown
of our current HIV classification scheme…
an alignment of the 132 nearly full-length M group sequences publicly available
in the HIV database alignment, spanning a region from the start of gag
to the end of env, there are a total of 7667 bases in HXB2.
HXB2 is a sequence derived from the first HIV-1 isolate and is a standard
reference strain. Roughly 13% (992) of the positions in HXB2 have deletions in
one or more of the other 131 HIV-M group sequences, leaving 6675 positions in
HXB2 that do not contain any deletions in the alignment. Of these 6675 alignable positions, 2301 bases (30% of the
total 7667 bases) are invariant, and 4374 (57%) of the positions have
substitutions… [Note: The HXB2, the “standard [HIV genome] reference
strain”, is nothing more than the clone of a cDNA of a poly(A)-RNA which in
sucrose density gradients bands at a density of 1.16gm/ml, the band considered
to be “purified HIV”.(5) The
band may contain no particles with the morphological characteristics of
retroviruses, (6) or it may predominantly contain microvesicles, that is,
cellular fragments containing poly(A)-RNA among which are interspersed particles
having some but not all the morphological characteristics attributed to the
“HIV” particles. (7, 8)]
kinds of viral evolution have been observed in human hosts over the last
century, which have been termed antigenic drift and antigenic shift.
Antigenic drift is the gradual change in the nucleotide sequence which is
due to point mutations accumulating over time.
Normally, changes made in the influenza vaccine are made in response to
the antigenic drift of the virus. Antigenic
shift, on the other hand, is an abrupt change in the serological and genetic
properties of the virus due to the introduction of new HA or NA subtypes into
previously unexposed populations. Currently,
two influenza A subtypes are found co-circulating in the human population, H3N2,
a result of an antigenic shift in 1968, and H1N1, a result of a re-introduction
of an H1N1 strain in 1977 similar to H1N1 strains circulating around
1950…….In the years spanning 1968-2001, the H3N2 component of the influenza
vaccine was changed a total of 17 times, in one case necessitated by antigenic
drift of as little as 3 amino acids substitutions in the 307 amino acid HA1
component of HA …
influenza, like HIV, is a rapidly evolving virus, a comparison of HIV and
influenza A evolution reveals very different patterns.
HIV evolution is characterised by a radial spread outward from an
ancestral node, while influenza is characterised by bottlenecks and global drift
from year to year. Within a single 9 month flu season, little variation was
typically found between geographically distinct influenza isolates after the
emergence of the epidemic strain. HIV,
on the other hand, shows increasing genetic diversity within a population
through time. A phylogenetic tree
of HA sequences sampled world-wide in 1996 shows much less diversity than a
sampling of subtype B HIV-1 envelope sequences from a single city, Amsterdam in
1990-1991. In stark contrast, a
sampling of HIV sequences from the Democratic Republic of the Congo in 1997
shows extraordinary diversity, with virtually all HIV subtypes co-circulating in
one geographic region. The
diversity of influenza sequences world-wide in any given year appears to be
roughly comparable to the diversity of HIV sequences found within a single
infected individual at one time point. Thus,
while influenza does have a relatively fast rate of mutation when measured over
decades, the vaccine for any given year is targeted towards a relatively
homogenous viral population. Small
numbers of changes in the viral amino acid sequence at antigenic sites require a
change in the vaccine strain to induce an immunologically appropriate response
for currently circulating strains. Thus
the diversity which an HIV-1 vaccine must counter through stimulating a broadly
reactive immune response is far greater than the diversity countered by the
influenza vaccine. If current
evolutionary trends continue, the situation will only become worse from a HIV
vaccine design standpoint. This is
daunting when considered in the context of the small number of amino acid
substitutions that result in a loss of antigenic cross-reactivity sufficient to
diminish influenza vaccine efficacy...
comparison between HIV and influenza virus illustrates the extraordinary scale
of HIV variation, and underscores the importance of exploring innovative HIV
vaccine strategies.” (2)
Foley wrote: “If the Perth group, or anyone else is interested in learning
about HIV-1, HIV-2 or other lentiviruses, I would be happy to help them
is great news!!! In all our rapid
responses we have been asking for help and are willing to be educated.
To begin then, would you please provide us with the following information
which we have repeatedly asked for but have received no reply.
All learning begins with being educated in the basics.
The basic information we have been repeatedly asking for is the
A few references which prove that the “purified HIV”, that is, the 1.16gm/ml
band from which the “HIV” genome and proteins originated, contains particles
in which “No apparent differences in physical appearance could be discerned”
and the particles have the morphology of retroviruses.
A few references that prove: (i) that the molecules used in “cloning of a
complete viral [HIV] genome” originated from HIV particles; (ii) that the HIV
“Genetic Sequences” in his databases originated from HIV particles.
A few references which prove that the HIV antibody tests are specific. To claim
proof for specificity there MUST BE at least one study and a few confirmatory
studies where the antibody antigen reaction (assuming that the antigens are HIV)
is compared with the present or absence of HIV, that is, with HIV
study must include a statistically significant number of both patients who have
AIDS as well as patients who do not have AIDS but are sick.
In addition, the tests must be done blind.
A few references which prove that HIV is heterosexually transmitted. Any study
claiming proof for heterosexual transmission MUST satisfy at least the following
· Be prospective;
tests which have been proven to be specific;
a statistically meaningful population;
results must be statistically significant and must exclude any other possible
route of infection;
should be at least a few confirmatory studies.
Foley wrote: “But people who only seek to spread disinformation about AIDS
deserve no further response from me.”
the beginning of the AIDS era, we put forward an alternative theory of AIDS,
most if not all of whose predictions have been fulfilled. (9, 10) In our view, this does not represent seeking to
“spread disinformation about AIDS”.
Furthermore, this debate has not been about AIDS but about “HIV” for
which we have put forward many questions. Again,
in our view, questions and the factual answers to them can only strengthen a
scientific view which is correct to begin with.
(1) Kozal MJ, Shah N, Shen N, Yang R, Fucini R, Merigan TC, Richman DD, Morris D, Hubbell E, Chee M, Gingeras TR. (1996). Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat Med 2:753-759.
Korber B, Gaschen B, Yusim K, Thakallapally R, Kesmir C, Detours V.
(2001). Evolutionary and immunological implications of contemporary HIV-1
variation. British Medical Bulletin 58:
Weiss RA. (2003). HIV and AIDS: looking ahead. Nature
Medicine 9: 887-891.
Sala M, Wain-Hobson S. (2000). Are RNA Viruses Adapting or Merely
Changing? J Mol. Evol. 51:12-20.
BH, Shaw GM, Arya SK, Popovic M, Gallo RC, Wong-Staal F. (1984).
Molecular cloning and characterization of
the HTLV-III virus associated with AIDS. Nature
Tahi D. (1998). Did Luc
Montagnier discover HIV? Text of video interview with Professor Luc Montagnier
at the Pasteur Institute July 18th 1997. Continuum 5:30-34. www.virusmyth.net/aids/data/dtinterviewlm.htm
Bess JW Jr, Gorelick RJ, Bosche WJ, Henderson LE, Arthur LO. (1997).
Microvesicles are a source of contaminating cellular proteins found in purified
HIV-1 preparations. Virology
Gluschankof P, Mondor I, Gelderblom HR, Sattentau QJ. (1997).
Cell Membrane Vesicles Are a Major Contaminant of Gradient-Enriched Human
Immunodeficiency Virus Type-1 Preparations. Virology
Papadopulos-Eleopulos E. (1988). Reappraisal of AIDS: Is the oxidation
caused by the risk factors the primary cause? Medical Hypotheses 25:151-162.
Papadopulos-Eleopulos E. (1998). Looking back on the oxidative stress
theory of AIDS. Continuum 5:30-35. www.theperthgroup.com/aids/lookingback.doc
Competing interests: None declared