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Re: Politics vs. science.

Re: Politics vs. Science

In 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”.”

We 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”.

Brian 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:…’

It 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)

Brian Foley wrote: “The HIV-1 M group and O group viruses do indeed look identical to each other when viewed by electron microscopy.”

We 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.

Brian 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 dismissed.”

DNA 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.

Brian 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 genomes.”

As 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 Laboratory:

“HIV generates variants at a far greater rate than do other RNA viruses such as measles, polio and even infuenza.” (3)

“By 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).

“HIV-1 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… 

HIV-1 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…

In 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)] 

Two 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 …

Although 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...

A comparison between HIV and influenza virus illustrates the extraordinary scale of HIV variation, and underscores the importance of exploring innovative HIV vaccine strategies.” (2)

Brian 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 learn.”

This 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 following:

(a) 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.

 (b) 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.

 (c) 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 isolation/purification.    This 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.

 (d) A few references which prove that HIV is heterosexually transmitted. Any study claiming proof for heterosexual transmission MUST satisfy at least the following conditions:

·         Be prospective;

·         Use tests which have been proven to be specific;

·         Have a statistically meaningful population;

·         The results must be statistically significant and must exclude any other possible route of infection;

·         There should be at least a few confirmatory studies.

Brian Foley wrote: “But people who only seek to spread disinformation about AIDS deserve no further response from me.”

At 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.

References

(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.

(2)   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: 19-42

(3)   Weiss RA. (2003). HIV and AIDS: looking ahead. Nature Medicine 9: 887-891.

(4)   Sala M, Wain-Hobson S. (2000). Are RNA Viruses Adapting or Merely Changing? J Mol. Evol. 51:12-20.

(5)   Hahn 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 312: 166-169

(6)   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

(7)   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  Mar 31;230(1):134-44.

(8)   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  230: 125-133.

(9)   Papadopulos-Eleopulos E. (1988). Reappraisal of AIDS: Is the oxidation caused by the risk factors the primary cause? Medical Hypotheses 25:151-162.

(10)           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