Re: Re: Re: Re: Re: Two questions to Brian Foley 6 May 2004
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Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos, NM 87545

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Re: Re: Re: Re: Re: Re: Two questions to Brian Foley

The Perth group wrote:

“We are glad that in his rapid response “ Re: Re: Re: Two questions to Brian Foley”, 4th May 2004, Brian Foley finally agrees with us that the “HIV” RNA is a poly(A)-RNA. Is it true that the “HIV” poly(A)-RNA, that is, the “HIV” genome, originated from the 1.16gm/ml band? Yes or No? “

Yes, HIV genomes are found in the 1.16 g/ml band. But most infectious molecular clones of HIV-1, HIV-2, SIV, other lentiviral and other retroviral genomes are not harvested directly from the 1.16 g/ml band. Instead, they are produced from integrated proviral genomes [1] or extrachromosomal circular dsDNA pre-integration genomes isolated using the method of Hirt [2,3].

The Perth group wrote:

“Brian Foley wrote: “An infectious molecular clone of HIV, is a complete nondefective genome…Infectious molecular clones of HIVs must be proven to produce infectious virions”.

These are two distinctly different notions of an “infectious molecular clone”. Would Brian Foley please tell us which, if any, is correct?
…”

I do not understand why the Perth group thinks these notions are incompatible with each other. Do they believe that a partial or defective genome should be able to produce infectious virions? Almost every infectious molecular clone of HIV that I am aware of has been used in dozens of studies, they are sequenced [4,5], probed or used as probes in Southern and Northern blots [1,2], proven to produce infectious virions [6], modified with site-directed mutagenesis to determine exactly which bases or codons encode each function of the virus [7,8], used to prepare proteins that are then shown to react with antibodies from AIDS patients and some sex partners of AIDS patients but not heathly blood donors [9,10], etc…

I would not accept any one of these properties alone as “proof” of the isolation of HIV-1 and its role as the causative agent of the AIDS pandemic. Each use of the clones just adds one more bit of information to the overall picture, until at some point it becomes clear that there is no other logical explanation. As I have previously stated, the clones alone may be able to prove that HIV is the cause of AIDS, but much other work with conventional epidemiology such as contact tracing was critical in determining, before HIV-1 was ever isolated, that AIDS was an infectious syndrome and not an environmental problem or “lifestyle” disease as Peter Duesberg, Mohammed Al-Bayati, the Perth group and others insist. Molecular clones of HIVs and SIVs have been used to re-confirm those earlier findings in numerous ways.

1: Alizon M, Sonigo P, Barre-Sinoussi F, Chermann JC, Tiollais P,
Montagnier L, Wain-Hobson S.
Molecular cloning of lymphadenopathy-associated virus.
Nature. 1984 Dec 20-1985 Jan 2;312(5996):757-60.
PMID: 6096717

2: Hahn BH, Shaw GM, Arya SK, Popovic M, Gallo RC, Wong-Staal F.
Molecular cloning and characterization of the HTLV-III virus associated
with AIDS.
Nature. 1984 Nov 8-14;312(5990):166-9.
PMID: 6095086

3: Hirt B.
Selective extraction of polyoma DNA from infected mouse cell cultures.
J Mol Biol. 1967 Jun 14;26(2):365-9.
PMID: 4291934

4: Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF,
Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, et al. Related
Complete nucleotide sequence of the AIDS virus, HTLV-III.
Nature. 1985 Jan 24-30;313(6000):277-84.
PMID: 2578615

5: Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M.
Nucleotide sequence of the AIDS virus, LAV.
Cell. 1985 Jan;40(1):9-17.
PMID: 2981635

6: Fisher AG, Collalti E, Ratner L, Gallo RC, Wong-Staal F.
A molecular clone of HTLV-III with biological activity.
Nature. 1985 Jul 18-24;316(6025):262-5.
PMID: 2410792

7: Powell MD, Ghosh M, Jacques PS, Howard KJ, Le Grice SF, Levin JG.
Alanine-scanning mutations in the "primer grip" of p66 HIV-1 reverse
transcriptase result in selective loss of RNA priming activity.
J Biol Chem. 1997 May 16;272(20):13262-9.
PMID: 9148945

8: Ghosh M, Williams J, Powell MD, Levin JG, Le Grice SF.
Mutating a conserved motif of the HIV-1 reverse transcriptase palm
subdomain alters primer utilization.
Biochemistry. 1997 May 13;36(19):5758-68.
PMID: 9153416

9: Sarngadharan MG, Popovic M, Bruch L, Schupbach J, Gallo RC.
Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III)
in the serum of patients with AIDS.
Science. 1984 May 4;224(4648):506-8.
PMID: 6324345

10: Klatzmann D, Cavaille-Coll M, Brunet JB, Rozenbaum W,
Kernbaum S, Barre-Sinoussi F, Chermann JC, Montagnier L, Gluckman JC.
Immune status of AIDS patients in France: relationship with lymphadenopathy
associated virus tropism.
Ann N Y Acad Sci. 1984;437:228-37.
PMID: 6335952

Competing interests: None declared