Re: Give us the "HIV" "structure", please. 13 October 2004
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Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos, NM 87545

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Re: Re: Give us the "HIV" "structure", please.

The Perth group wrote:

"… If the retroviral poly(A)-RNA can be reverse transcribed, the cDNA integrated into the cellular genome, then transcribed into poly(A)-RNA and translated (the proviral theory of retroviruses) why, given the right conditions, the same thing cannot happen with cellular poly(A)-RNA?

What specific properties do the retroviral poly(A)-RNAs have which cannot be found in cellular poly(A)-RNAs?
…”

First of all, the retroviral RNA is reverse transcribed into an RNA:DNA heteroduplex and then converted to closed circular double stranded DNA before it is integrated into the genome using the virus-encoded integrase enzyme.

The Perth group pretend to believe in endogenous retroviruses, when none have ever come remotely close to being “isolated” by the fictional protocol which the Perth group claims to want done before they will believe in HIV-1 or HIV-2. The Perth group seems to imply that they believe that endogenous retroviruses have been observed to be reverse translated and re-integrated into the human genome during the lifetime of a human (as opposed to there being evidence that this process has taken place sometime in the past several million years but not in the past 100 years). It would not surprise me if there is some evidence that someone has observed such an event, but I am not aware of any such observation.

Most human endogenous retroviruses (HERVs), retroposons and other retroviral-like elements in the human genome are inactive and/or defective. One of the HERVs which is believed to have some activity in humans does not encode a functional integrase (1). Another is known to have a functional integrase, because it can complement an integrase defect in an HIV-1 genome (2), but as far as I know, this HERV has not been observed to move to new sites in the human genome.

Nicholas Bennett, myself, Chris Noble and others have been patiently attempting to explain to the Perth group that there are many features of retroviruses that are all required to make an infectious, replication-competent particle or infectious molecular clone. They include complete open reading frames for the structural proteins (Gag capsid, Gag nucleocapsid (3), Envelope (4) and sometimes others) and enzymes (Reverse transcriptase, Integrase (5), Protease and sometimes others), a reverse transcription primer binding site (lentiviruses all use the Lys-3 tRNA as primer (6)), poly-purine tracts involved in ds-DNA formation (7), promoters and mRNA transcription start sites, poly-adenylation signals and elements such as the TAR element which suppress premature mRNA termination and polyadenylation from the 5’ Poly-A signal (8). HIV-1 and HIV-2 also have several genes which encode regulatory proteins (such as Tat which binds to the TAR element), and proteins which enable the virus to evade cellular restrictions (such as Vif which aids in preventing CEM15 from degrading the RNA:DNA heteroduplex (9)).

The Perth group cleverly claims to be ignorant of all aspects of epidemiology, virology and molecular biology when they think it aids their cause. On the other hand they are deluded about being the world’s leading authorities on retroviral “isolation”, claiming that they can see some rules for retrovirus isolation in a pair of 1977 papers that in fact contain no such rules. It would be very interesting to see a discussion of why the Perth group pretends to believe in HERVs but not HIVs. No exogenous virus has ever been “proven” to exist by the Perth group’s fictional method, and endogenous viruses are much more difficult to work with.

Ignorance of molecular biology is completely understandable and acceptable. Hardly anyone understands how DNA sequencing and monoclonal antibodies have revolutionized the world of biological research. What is unusual, and in my opinion unacceptable, is that the Perth group are apparently deluded into believing that their ignorance qualifies them to be the world’s authorities on retroviruses, and to give advice to the president of South Africa on how he should deal with the AIDS epidemic.

REFERENCES:

1: Kjellman C, Sjogren HO, Salford LG, Widegren B
HERV-F (XA34) is a full-length human endogenous retrovirus
expressed in placental and fetal tissues.
Gene. 1999 Oct 18;239(1):99-107.
PMID: 10571039

2: Ogata T, Okui N, Sakuma R, Kobayashi N, Kitamura Y
Integrase of human endogenous retrovirus K-10 supports the replication
of replication-incompetent Int- human immunodeficiency virus type 1 mutant.
Jpn J Infect Dis. 1999 Dec;52(6):251-2.
PMID: 10738367

3: Morikawa Y.
HIV capsid assembly.
Curr HIV Res. 2003 Jan;1(1):1-14.
PMID: 15043208

4: Zhu X, Borchers C, Bienstock RJ, Tomer KB.
Mass spectrometric characterization of the glycosylation pattern of
HIV-gp120 expressed in CHO cells.
Biochemistry. 2000 Sep 19;39(37):11194-204.
PMID: 10985765

5: Chiu TK, Davies DR.
Structure and function of HIV-1 integrase.
Curr Top Med Chem. 2004;4(9):965-77.
PMID: 15134551

6: Kleiman L.
tRNA(Lys3): the primer tRNA for reverse transcription in HIV-1.
IUBMB Life. 2002 Feb;53(2):107-14.
PMID: 12049192

7: McWilliams MJ, Julias JG, Sarafianos SG, Alvord WG, Arnold E,
Hughes SH.
Mutations in the 5' end of the human immunodeficiency virus type 1
polypurine tract affect RNase H cleavage specificity and virus titer.
J Virol. 2003 Oct;77(20):11150-7.
PMID: 14512562

8: Elangovan B, Subramanian T, Chinnadurai G
Functional comparison of the basic domains of the Tat proteins of
human immunodeficiency virus types 1 and 2 in trans activation.
J Virol. 1992 Apr;66(4):2031-6.
PMID: 1548750

9: Xu H, Svarovskaia ES, Barr R, Zhang Y, Khan MA, Strebel K, Pathak VK.
A single amino acid substitution in human APOBEC3G antiretroviral
enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion.
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5652-7.
PMID: 15054139

Competing interests: None declared