More repetition. 5 November 2003
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Christopher J Noble,
postdoctoral fellow
Bern Switzerland

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Re: More repetition.

Eleni Papadopulos-Eleopulos writes: "Yet when we asked for published references supporting the 50% variations, in the only reference Christopher Noble provided and as the above quote shows, "the authors compared not only human influenza A viruses but also influenza A viruses of birds obtained at different times from around the world" and "the sequence differences were based upon several assumptions". So where are the published references "of examples of human influenza A hemagglutinins that differ by approximately 50%"? Is it sufficient to report genomic variability from databases or should not we also ask what are the biological consequences of these variabilities? The question also arises are all these variabilities real or are at least some of them the result of errors in PCR and phylogenetic tree analysis?"

I have already explained several times that the two subtypes of hemagglutinin that are currently co-circulating in humans are as divergent from each other as any other pair of subtypes. Your objections are just ad hoc excuses. You want to ignore the evidence because it contradicts your claims.

The Influenza sequence database ( http://www.flu.lanl.gov/search/ ) contains 1348 sequences of Influenza A hemagglutinin isolated from human hosts. I have previously picked an H1N1 and an H3N2 isolate at random and shown that the similarity between these two sequences is somewhere around 50%.

If you take any other pair of H1 and H3 sequences the results will be exactly the same - around 50% similarity. Are you claiming that all of these sequences are just accidents? A large proportion of these sequences have been published in peer reviewed journals. The methods for viral isolation and sequencing are published in these papers. The fact that they are also submitted to a sequence database that is available online is hardly a reason to question the validity of the evidence.

Indeed, the only reason you are questioning the evidence is that it contradicts your passionately defended beliefs. You simply refuse to admit that you are wrong.

When you stated "The type 3 Sabin poliovirus vaccine differed from its neurovirulent progenitor at only 10 nucleotide positions after 53 in vitro and 21 in vivo passages in monkey tissues. In 1977, H1N1 influenza A virus reappeared in the human population after 27 years of dormancy with sequences mainly identical to those of the 1950s virus" at no time did you question the accuracy of the sequencing or the vailidity of the alignments.

Now when you are presented with evidence that The Sabin poliovirus types 1-3 differ from each other by approximately 20% (1) and that the H1 and H3 subtypes of influenza A hemagglutinin differ by about 50% all of a sudden you start questioning the evidence.

Several researchers, including David Steinhauer have studied Influenza hemagglutinin and its role in mebrane fusion. (2) To determine what parts of the gene sequence are critical for function you can do at least two things: look at many sequences and see which residues are completely conserved, site directed mutagenesis.

In the case of hemagglutinin there are 11 amino acids that are completely conserved amongst all subtypes. Steinhauer and his colleagues have then used reverse genetics to study influenza viruses where these amino acid residues are changed with site directed mutagenesis.

When Peter Duesberg stated "And, in that regard, HIV is exactly -- and I'm pointing out exactly -- the same as all other viruses. You'll find the same thing with flu and with polio and with measles and with mumps and with other retroviruses in chickens and in mice." he was entirely correct. All RNA viruses are highly variable. There are only small segments of the genome - around 10 amino acids - that are completely conserved in all isolates. These sequences are essential for viral replication or infectivity. Change them and the virus is not capable of replicating or infecting host cells efficiently. However, in other parts of the genome mutations accumulate over time. The divergent subtypes of Influenza, polio and human papilloma virus have all arisen in this manner.

You still refuse to answer simple questions regarding the genomes of influenza and polio viruses. Now you expect me to answer rhetorical questions.

"Would Christopher Noble tell us whether in his view Montagnier proved the existence of a retrovirus "HIV" in 1983? (8) If Christopher Noble avoids answering this question it will mean that in his view no such proof can be found in the 1983 paper by Montagnier and his associates."

I have never stated that this paper "proved" anything. There is no such thing as absolute proof in science. Certainly nobody can "prove" something to somebody that does not want to believe it. Montagnier did however present evidence that a virus, later called HIV, can be found in patients that have AIDS. Since 1983 the amount of evidence that has accumulated is overwhelming.

In exactly the same way there is no such thing as absolute proof for the existence of electrons. I am curious to know why you are not demanding "proof" for the existence of electrons.

(1) Toyoda H, Kohara M, Kataoka Y, Suganuma T, Omata T, Imura N, Nomoto A. Complete nucleotide sequences of all three poliovirus serotype genomes. Implication for genetic relationship, gene function and antigenic determinants. J Mol Biol. 1984 Apr 25;174(4):561-85.

(2) Cross KJ, Wharton SA, Skehel JJ, Wiley DC, Steinhauer DA. Studies on influenza haemagglutinin fusion peptide mutants generated by reverse genetics. EMBO J. 2001 Aug 15;20(16):4432-42.

Competing interests: None declared