The Perth Group "answer" to Christopher Noble 5 September 2003
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Christopher J Noble,
postdoctoral fellow
Bern Switzerland

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Re: The Perth Group "answer" to Christopher Noble

Eleni Papadopulos-Eleopulos wrote: "When we wrote "the human papilloma virus' genome is even more variable then the "HIV" genome", by variability we mean the "variation at a given time" or "levels of divergence" which Christopher Noble uses and not mutation rates or evolution rates which are changes in time."

This is not consistent with what you previously wrote: ""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)."

Eleni Papadopulos-Eleopulos further writes: "In other words: While "HIV-1" is said to be a unique virus..."

Who said this? You?

The Halpern review (1) outlines a taxonomic classification of SIV/HIV with type, group and subtype levels. HIV-1 is divided into groups M, N and O which are then divided into subtypes. HIV-1 group M is clearly different to HIV-1 group O. HIV-1 group M subtype B is clearly not the same as HIV-1 group M subtype F. However they all share the same genome organisation and show obvious phylogenetic relationships.

Eleni Papadopulos-Eleopulos further writes: "The reference in which we said it is stated that even a 1% difference is considered to represent "extreme heterogeneity of viral populations" (8) was given before in our rapid responses ""HIV" genome, clones and sequences" (18 July 2003) and "The "HIV" and influenza A virus genomes" (26 July 2003). "

I have gone to the trouble of posting links to the Entrez Nucleotide database so that anyone can download the genetic sequences of the 3 Sabin poliovirus types. http://www.ncbi.nlm.nih.gov:80/entrez/que ry.fcgi?cmd=Retrieve&db=nucleotid e&list_uids=27085396&dopt=GenBank http://www.ncbi.nlm.nih.gov:80/entrez/que ry.fcgi?cmd=Retrieve&db=nucleotide&li st_uids=27085398&dopt=GenBank http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=27085400&dopt=GenBank

The three poliovirus types differ from each other by approximately 20% at the nucleotide level.

This directly falsifies your claim that "By comparison, two RNA containing viruses (polio and influenza, the latter after 27 years of dormancy,) vary by less than 1%"

You have not responded to this point yet so I will ask you a direct unambiguous question. Do the three Sabin polioviruses differ from each other by more than 1%? Yes or No?

Continuing to cite the review by Steinhauer (2) and claiming that it says that "the genomes of the most variable RNA viruses do not differ by more than 1%" will not help. It does not state this anywhere in the review.

The figure of 1% refers to a study by Cattaneo et al. It refers to the intrahost variation of the M protein coding sequence of the Measles Virus in the brain tissue of patients suffering from SSPE.

"In addition we note that as much as 1% of the nucleotides differed between two overlapping clones from the same brain."

The genetic distance between isolates of different measles types is much greater than 1%.

In contrast to the Cattaneo study you quote 40% as the interhost genetic difference between the most divergent isolates of HIV.

You are comparing intrahost variation for measles with interhost variation for HIV.

Eleni Papadopulos-Eleopulos further writes: "It is our view that we have been answering Christopher Noble and everyone else who has put questions to us, paragraph by paragraph."

I do not share that view.

I have provided you with the sequences for different poliovirus isolates that differ by 20% at the nucleotide level.

Yet you continue to claim that "the genomes of the most variable RNA viruses do not differ by more than 1%".

You claim that you have provided evidence for this claim when in fact you have not.

I will ask you one more time for a citation to support your claim that "the genomes of the most variable RNA viruses do not differ by more than 1%".

Please answer the question.

1. Halpern AL. Comparison of papillomavirus and immunodeficiency virus evolutionary patterns in the context of a papillomavirus vaccine. (2000) J. Clinical Virology 19:43-56.

2. Steinhauer DA, Holland JJ. Rapid evolution of RNA viruses. (1987) Annual Review of Microbiology 41:409-433.

3. Cattaneo R, Schmid A, Rebmann G, Baczko K, Ter Meulen V, Bellini WJ, Rozenblatt S, Billeter MA. Virology. 1986 Oct 15;154(1):97-107.

Competing interests:   None declared