Re: Re: Basic requests which remain unanswered by Brian Foley and Christopher Noble 23 March 2004
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Brian T. Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos, NM USA 87545

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Re: Re: Re: Basic requests which remain unanswered by Brian Foley and Christopher Noble

The Perth Group Wrote:

"In our rapid response "Basic requests which remain unanswered by Brian Foley and Christopher Noble, 24 December 2003, we tried to re-direct the debate to the basics and ask for references with data which prove some of the fundamental claims regarding HIV.
To date neither Brian Foley nor Christopher Noble nor any of the other renown HIV experts, who apparently follow this debate, have given us such data. Does their silence indicate that such data does not exist? "

No. It means that I do not feel that it is a productive use of my time to spoon feed you all of the research that has been done on HIV-1, HIV-2 and other lentiviruses over the past 20 years.

I will spend a little time answering your questions of Dec 24, 2003 now:

1. "Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity?". ("A simple request from the Perth Group" - 5th June)

ISOLATION:
Answered 23 May 2003
What part of "infectious molecular clone" do you fail to understand?
How do you think the 3D strucutres of HIV-1, HIV-2 and SIV proteins have been determined using X-ray crystalography, if not with purified HIV-1, HIV-2 and SIV proteins?
Why is it that no virus has ever been "isolated" following the exact protocol you describe? And why, if no virus has ever been "isolated" to your satisfaction, do you only question HIV/AIDS and not other virus/disease (or syndrome) relationships? Which of the following could have been published without the study of pure isolates?
(1) Hill CP, Worthylake D, Bancroft DP, Christensen AM, Sundquist WI.
Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly.
Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104.
(2) Morikawa Y, Zhang WH, Hockley DJ, Nermut MV, Jones IM.
Detection of a trimeric human immunodeficiency virus type 1 Gag intermediate is dependent on sequences in the matrix protein, p17.
J Virol. 1998 Sep;72(9):7659-63. (3) Gatanaga H, Suzuki Y, Tsang H, Yoshimura K, Kavlick MF, Nagashima K, Gorelick RJ, Mardy S, Tang C, Summers MF, Mitsuya H.
Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors.
J Biol Chem. 2002 Feb 22;277(8):5952-61. Epub 2001 Dec 10.
(4) Turner BG, Summers MF.
Structural biology of HIV.
J Mol Biol. 1999 Jan 8;285(1):1-32. Review.
(5) Reed-Inderbitzin E, Maury W.
Cellular specificity of HIV-1 replication can be controlled by LTR sequences.
Virology. 2003 Sep 30;314(2):680-95.
(6) Komoto S, Tsuji S, Ibrahim MS, Li YG, Warachit J, Taniguchi K, Ikuta K.
The vpu protein of human immunodeficiency virus type 1 plays a protective role against virus-induced apoptosis in primary CD4(+) T lymphocytes.
J Virol. 2003 Oct;77(19):10304-13.
(7) Rue SM, Roos JW, Amzel LM, Clements JE, Barber SA.
Hydrogen bonding at a conserved threonine in lentivirus capsid is required for virus replication.
J Virol. 2003 Jul;77(14):8009-18.
(8) von Gegerfelt AS, Liska V, Li PL, McClure HM, Horie K, Nappi F, Montefiori DC, Pavlakis GN, Marthas ML, Ruprecht RM, Felber BK.
Rev-independent simian immunodeficiency virus strains are nonpathogenic in neonatal macaques.
J Virol. 2002 Jan;76(1):96-104.
(9) Pavlakis GN
The Molecular Biology of Human Immunodeficiency Virus Type 1.
In: De Vita Jr VT, Hellman S, Rosenberg SA eds.
AIDS: Biology, Diagnosis, Treatment and Prevention.
Philadelphia: Lippincott-Raven Publ., 1997. p. 45-74. (10) Levy J
HIV and the Pathogenesis of AIDS, 2nd Edition
Book ISBN: 1-55581-122-1 ASM Press 1997

SEXUAL TRANSMISSION:
Answered Numerous time above, for example April 10, 2003:
(1) Jacquez JA, Koopman JS, Simon CP, Longini IM Jr.
Role of the primary infection in epidemics of HIV infection in gay cohorts.
J Acquir Immune Defic Syndr 1994; 7(11):1169-84.
(2) Yerly S et al.
HIV drug resistance and molecular epidemiology in patients with primary HIV infection.
Abstract 754, 8th Conference on Retroviruses and Opportunistic Infections. Chicago 2001.
(3) Pilcher CD et al.
Sexual transmission during the incubation period of primary HIV infection.
JAMA 2001; 286(14): 1713-4.
(4) Quinn TC, Wawer MJ, Sewankambo NK, et al.
Viral load and heterosexual transmission of human immunodeficiency virus type 1.
N Engl J Med 342(13):921-9, 2000.
(5) Pilcher CD, Shugars DC, Fiscus SA, Miller WC, Menezes P, Giner J, Dean B, Robertson K, Hart CE, Lennox JL, Eron JJ Jr, Hicks CB.
HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health.
AIDS 2001 May 4;15(7):837-45.
(6) Chakraborty H, et al.
Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.
AIDS 2001: 15(5):621-7.
(7) Leitner T, Escanilla D, Franzen C, Uhlen M, Albert J.
Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis.
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10864-9.
(8) Machuca R, Jorgensen LB, Theilade P, Nielsen C.
Molecular investigation of transmission of human immunodeficiency virus type 1 in a criminal case.
Clin Diagn Lab Immunol. 2001 Sep;8(5):884-90.
(9) Birch CJ, McCaw RF, Bulach DM, Revill PA, Carter JT, Tomnay J, Hatch B, Middleton TV, Chibo D, Catton MG, Pankhurst JL, Breschkin AM, Locarnini SA, Bowden DS.
Molecular analysis of human immunodeficiency virus strains associated with a case of criminal transmission of the virus.
J Infect Dis. 2000 Sep;182(3):941-4. Epub 2000 Aug 17.
(10) Albert J, Wahlberg J, Leitner T, Escanilla D, Uhlen M.
Analysis of a rape case by direct sequencing of the human immunodeficiency virus type 1 pol and gag genes.
J Virol. 1994 Sep;68(9):5918-24.
(11) Sato H, Shiino T, Kodaka N, Taniguchi K, Tomita Y, Kato K, Miyakuni T, Takebe Y.
Evolution and biological characterization of human immunodeficiency virus type 1 subtype E gp120 V3 sequences following horizontal and vertical virus transmission in a single family.
Virol. 1999 May;73(5):3551-9.
(12) Albert J, Wahlberg J, Leitner T, Escanilla D, Uhlen M.
Analysis of a rape case by direct sequencing of the human immunodeficiency virus type 1 pol and gag genes.
J Virol. 1994 Sep;68(9):5918-24.
(13) Robbins KE, Weidle PJ, Brown TM, Saekhou AM, Coles B, Holmberg SD, Folks TM, Kalish ML.
Molecular analysis in support of an investigation of a cluster of HIV-1-infected women.
AIDS Res Hum Retroviruses. 2002 Oct 10;18(15):1157-61.
(14) Kato S, Saito R, Hiraishi Y, Kitamura N, Matsumoto T, Hanabusa H, Kamakura M, Ikeda Y, Negishi M.
Differential prevalence of HIV type 1 subtype B and CRF01_AE among different sexual transmission groups in Tokyo, Japan, as revealed by subtype-specific PCR.
AIDS Res Hum Retroviruses. 2003 Nov;19(11):1057-63.
(15) Tovanabutra S, Watanaveeradej V, Viputtikul K, De Souza M, Razak MH, Suriyanon V, Jittiwutikarn J, Sriplienchan S, Nitayaphan S, Benenson MW, Sirisopana N, Renzullo PO, Brown AE, Robb ML, Beyrer C, Celentano DD, McNeil JG, Birx DL, Carr JK, McCutchan FE.
A new circulating recombinant form, CRF15_01B, reinforces the linkage between IDU and heterosexual epidemics in Thailand.
AIDS Res Hum Retroviruses. 2003 Jul;19(7):561-7.
(16) Tovanabutra S, Robison V, Wongtrakul J, Sennum S, Suriyanon V, Kingkeow D, Kawichai S, Tanan P, Duerr A, Nelson KE.
Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand.
J Acquir Immune Defic Syndr. 2002 Mar 1;29(3):275-83.
(17) Nelson KE, Rungruengthanakit K, Margolick J, Suriyanon V, Niyomthai S, de Boer MA, Kawichai S, Robison V, Celentano DD, Nagachinta T, Duerr A.
High rates of transmission of subtype E human immunodeficiency virus type 1 among heterosexual couples in Northern Thailand: role of sexually transmitted diseases and immune compromise.
J Infect Dis. 1999 Aug;180(2):337-43.
(18) Pedraza MA, del Romero J, Roldan F, Garcia S, Ayerbe MC, Noriega AR, Alcami J.
Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner.
J Acquir Immune Defic Syndr. 1999 Jun 1;21(2):120-5.
(19) Ragni MV, Faruki H, Kingsley LA.
Heterosexual HIV-1 transmission and viral load in hemophilic patients.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jan 1;17(1):42-5.

ANTIBODY SPECIFICITY:
(1) Zwick MB, Komori HK, Stanfield RL, Church S, Wang M, Parren PW, Kunert R, Katinger H, Wilson IA, Burton DR.
The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5.
J Virol. 2004 Mar;78(6):3155-61.
(2) Darbha R, Phogat S, Labrijn AF, Shu Y, Gu Y, Andrykovitch M, Zhang MY, Pantophlet R, Martin L, Vita C, Burton DR, Dimitrov DS, Ji X.
Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope.
Biochemistry. 2004 Feb 17;43(6):1410-7.
(3) Johnson WE, Sanford H, Schwall L, Burton DR, Parren PW, Robinson JE, Desrosiers RC.
Assorted mutations in the envelope gene of simian immunodeficiency virus lead to loss of neutralization resistance against antibodies representing a broad spectrum of specificities.
J Virol. 2003 Sep;77(18):9993-10003.
(4) Zhang PF, Bouma P, Park EJ, Margolick JB, Robinson JE, Zolla-Pazner S, Flora MN, Quinnan GV Jr.
A variable region 3 (V3) mutation determines a global neutralization phenotype and CD4-independent infectivity of a human immunodeficiency virus type 1 envelope associated with a broadly cross-reactive, primary virus-neutralizing antibody response.
J Virol. 2002 Jan;76(2):644-55.
(5) Chanbancherd P, Limpairojn N, de Souza MS, Jugsudee A, Julananto P, Tienamporn P, Leucha W, Tasaniyananda C, Brown AE.
Evaluation of a new fourth-generation microwell enzyme-linked immunosorbent assay for detection of HIV-1 subtype B and E antibodies.
Southeast Asian J Trop Med Public Health. 2001 Mar;32(1):177-9.
(6) D'Souza MP, Livnat D, Bradac JA, Bridges SH.
Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials.
AIDS Clinical Trials Group Antibody Selection Working Group.
J Infect Dis. 1997 May;175(5):1056-62.
(7) van Binsbergen J, Keur W, vd Graaf M, Siebelink A, Jacobs A, de Rijk D, Toonen J, Zekeng L, Afane Ze E, Gurtler LG.
Reactivity of a new HIV-1 group O third generation A-HIV-1/-2 assay with an unusual HIV-1 seroconversion panel and HIV-1 group O/group M subtyped samples.
J Virol Methods. 1997 Dec;69(1-2):29-37.
(8) Bhore AV, Sastry J, Patke D, Gupte N, Bulakh PM, Lele S, Karmarkar A, Bharucha KE, Shrotri A, Pisal H, Suryawanshi N, Tripathy S, Risbud AR, Paranjape RS, Shankar AV, Kshirsagar A, Phadke MA, Joshi PL, Brookmeyer RS, Bollinger RC Jr.
Sensitivity and specificity of rapid HIV testing of pregnant women in India.
Int J STD AIDS. 2003 Jan;14(1):37-41.
(9) Weber B, Gurtler L, Thorstensson R, Michl U, Muhlbacher A, Burgisser P, Villaescusa R, Eiras A, Gabriel C, Stekel H, Tanprasert S, Oota S, Silvestre MJ, Marques C, Ladeira M, Rabenau H, Berger A, Schmitt U, Melchior W.
Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.
J Clin Microbiol. 2002 Jun;40(6):1938-46.

2. "Where are the experiments which prove HIV isolation and thus the existence of the HIV genome, sexual transmission and antibody specificity? ("The request remains the same and is still pure and simple" - 12th June)

Answered again above.

3. "Where is the proof for HIV purification by any method?" ("Where is the proof for HIV purification by any method?" - 19th June)

Answered again above.

4. "Could Brian Foley or anyone else please give us a few of the "thousands" of references where HIV-1 has been separated "from the vast majority of other material", in other words, purified?" A further plea for references on HIV purification" - 9th July)

It is abundantly clear that you do not understand molecular biology, and therefor you cannot understand what an infectious molecular clone of HIV-1 or any other virus is. Could you please stop repeating yourseld, and tell me which concepts of cloning and sequecing genes (including the genes of HIV-1) you fail to understand?

5. "If so, we implore him [Brian Foley] to provide a few references that prove: (i) the molecules used in "cloning of a complete viral [HIV] genome" originated from HIV particles;

All clones of HIV-1 originated either from HIV-1 particles or from integrated proviral DNA. Only the infectious molecular clones can go on to produce new infectious HIV-1 particles.

Cloning the genome of HIV-1 is no different than cloning the genome of any other virus, nor cloning a specific gene such as the gene for human insulin. There is no requirement for having "pure" insulin, before the insulin gene can be cloned, for example.

Perhaps an example from another area of science could help. To use X-rays to diagnose tibia bone fractures in humans, we do not have to have 100% "pure" isolated human tibia bones, nor do we require that X-rays be "isolated". We can deduce, from the use of X-rays to diagnose fractures in femurs of humans or tibias of dogs, that the technique will work for diagnosing fractured tibias in humans. The fact that I cannot find the one scientific paper that "proves" that X-rays can be accurate and specific in diagnosing fractured human tibias, is not a valid reason for my questioning whether X-rays can in fact be used for that purpose.

The molecular biological techniques used to study HIV-1, HIV-2, SIV, HCV, SARS virus, polio viruses, and other viruses are not unique to viruses. They are used in nearly all areas of biology. Forensic DNA investigations of crime scenes do not require that the criminal nor the victim be "isolated" in order to tell if the DNA in some blood at a kitchen crime scene came from a human or some beef that was cooked for dinner. Just as human DNA is readily distinguishable from bovine DNA, so too is lentiviral DNA (or RNA) is readily distinguishable from T-cell leukemia virus DNA (or RNA).

HIV-1, HIV-2 and many other lentiviruses, as well as other non-lentivirus retroviruses have indeed been "isolated". The term "isolate" can be used to describe a 100% pure molecule such as a plasmid DNA molecule containing an infectious molecular clone of HIV-1. But most often, no molecule is made 100% pure, it is almost always found in an aqueous solution or with salt ions associated with it. The term "isolate" is more often used to describe a molecule or class of molecules being seperated from others of its kind. Think of a prisoner being "isolated" in a jail. The viruses of type A in petri dish A are "isolated" from the viruses of type B in petri dish B, such that A/B recombinants cannot be formed unless some material from dish A is transferred to dish B or visa versa. Whereas many bacteria form discrete colonies on the agar in petri dishes, many other organisms cannot be "isolated" using the streak-plating or dillution/plating techniques. This does not mean that those organisms cannot be "isolated", it only means that other methods besides streak/plating must be used.

Whole organisms, whether they are truly self-replicating like most bacteria, or they require tho cooperation of another organism as do viruses and some bacteria (or even mammals, which even when "cloned" require a living host uterus in which to develop) can be cloned. Production of new progeny form the naked DNA (or the isolated nucleus with DNA and chromatin proteins etc in the case of cloned eukaryotes) is indeed proof positive that the DNA came from the same type of organism as the progeny. A sheep nucleus put into a human cell will not produce a human. Likewise an HIV-1 M group subtype B infectious molecular clone will produce only HIV-1 M group subtype B virions when transfected into cell cultures.

ii) cloning of HIV;

(1) Kuhmann SE, Pugach P, Kunstman KJ, Taylor J, Stanfield RL, Snyder A, Strizki JM, Riley J, Baroudy BM, Wilson IA, Korber BT, Wolinsky SM, Moore JP.
Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor.
J Virol. 2004 Mar;78(6):2790-807.
(2) Buckley KA, Li PL, Khimani AH, Hofmann-Lehmann R, Liska V, Anderson DC, McClure HM, Ruprecht RM.
Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA.
Virology. 2003 Aug 1;312(2):470-80.
(3) Kourtis AP, Ibegbu CC, Scinicariello F, Oh CY, McClure HM.
SHIV-KB9 infection of rhesus monkeys does not always cause disease-contribution of host immune factors and thymic output.
Virology. 2002 Nov 10;303(1):47-57.
(4) Mukai T, Komoto S, Kurosu T, Palacios JA, Li YG, Auwanit W, Tatsumi M, Ikuta K.
Construction and characterization of an infectious molecular clone derived from the CRF01_AE primary isolate of HIV type 1.
AIDS Res Hum Retroviruses. 2002 May 20;18(8):585-9.
(5) Novelli P, Vella C, Oxford J, Daniels RS.
Construction and characterization of a full-length HIV-1(92UG001) subtype D infectious molecular clone.
AIDS Res Hum Retroviruses. 2002 Jan 1;18(1):85-8.
(6) Ndung'u T, Lu Y, Renjifo B, Touzjian N, Kushner N, Pena-Cruz V, Novitsky VA, Lee TH, Essex M.
Infectious simian/human immunodeficiency virus with human immunodeficiency virus type 1 subtype C from an African isolate: rhesus macaque model.
J Virol. 2001 Dec;75(23):11417-25.
(7) Gao F, Trask SA, Hui H, Mamaeva O, Chen Y, Theodore TS, Foley BT, Korber BT, Shaw GM, Hahn BH.
Molecular characterization of a highly divergent HIV type 1 isolate obtained early in the AIDS epidemic from the Democratic Republic of Congo.
AIDS Res Hum Retroviruses. 2001 Aug 10;17(12):1217-22.
(8) Takahoko M, Tobiume M, Ishikawa K, Ampofo W, Yamamoto N, Matsuda M, Tatsumi M.
Infectious DNA clone of HIV type 1 A/G recombinant (CRF02_AG) replicable in peripheral blood mononuclear cells.
AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1083-7.

(iii) the HIV "Genetic sequences" in his database originated from HIV particles?

See above. The citations I provided on heterosexual transmission, for example the one by Thomas Leitner (Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10864-9.) are also useful in this regard, because it shows that both the viral sequences and the transmission chains go hand-in-hand in co-validating each other.

We would be grateful if Brian Foley could provide us with references showing HIV-1 preparations on which "No apparent differences in physics appearance could be discerned among the viral particles in these regions" as Sinoussi et al did and with "a high degree of homogeneity" and "virtual absence of DNA" as Crawford et al did?. So we repeat "where is the proof for HIV purification by any method?" That is, give us the published references." ("References on HIV purification " - 3rd July)

Not all organisms on earth are identical. Most E. coli cells look identical to all other E. coli cells and they also look identical to Salmonella typhimurium cells. All humans probably look alike to a dog or a chimpanzee, but we humans tend to think we each look unique. Physical appearance is not the key to determining all biological properties of organisms. All lentiviruses look alike by electron microscopy, but there is no evidence that equine infectious anemia virus can infect primate cells, let alone cause disease in primates. Some retroviruses are spherical and symetrical so they appear the same no matter what orientation they are in. Lentiviruses have a cone-shaped core, and are thus not symetrical and do not appear identical viewed end-on or from the side.

There is no requirement that viral cultures appear to be 100% "pure" in order to study them. In fact retrovirus preparations that appear to be "pure" are most often comprised of heterogeneous populations of virus particles because the reverse transciptase is inaccurate and mutations accrue in the virus as it is grown in culture. This is one of the many reasons why the use of infectious molecular clones, rather than cultured virus, is preferable and in some cases abosolutely necessary for studying retroviruses.

6. "We are ignorant of the evidence which proves the existence of HIV. Would Christopher Noble please enlighten us with some references?" ("HIV" genomic variations - 31st July)

See above.

7. "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?. 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?. 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.

See above

(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.

See above.

(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.

I am not sure exactly what you are requiring here. Can you show me one example of a viral (preferably retroviral, but anyy virus will do) EIA, ELISA or Western Blot test kit (or even a test that has not yet been FDA-approved for serological testing of any species) that has met all of your criteria? Do the test kits that are the basis of slaughtering millions of chickens each year because they are seropositive for Avian Leukosis Virus serotype C meet your criteria for example? As far as I know, the requirements you are asking for are not only completely unnecessary but also impossible, such that no EIA or ELISA could possibly meet them.

(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." ("Re: Politics vs. Science" - 5th August)

Again, can you show me publications which meet those same criteria for any other disease or condition? Is there any such proof for example, that pregnancy is the result of heterosexual activity?

8. "As we have already pointed out to Brian Foley in our previous rapid response "HIV Genome, Clones and Sequences" (18 July 2003), what Montagnier?s and Gallo?s groups defined as "HIV" genome is nothing more than a poly(A)-RNA which in sucrose density gradients banded at the 1.16gm/ml. They claimed that the band represented "purified" virus but presented no EM proof. According to Montagnier the reason for this is because in the "purified" virus they could find no particles with the morphology typical of retroviruses?. Would Brian Foley please answer the following question: Isn?t it true that this is how the "HIV" genome was obtained? If not, would Brian Foley please tell us where we are wrong??. Since "HIV-1(MN)" has been used by laboratories around the world included Bess? laboratory, in his view would Brian Foley please tell us which of Gallo?s evidence proves the existence of "HIV-1(MN)"? "("Questions and Answers" - 13 October)

You should ask Robert Gallo about viruses that he isolated. But you could also look beyond 1983-1984 at viruses that have been isolated by hundreds of other groups around the world. Robert Gallo's lab was one of the first to isolate and characterize an HIV-1 M group subtype B virus, but since that time hundreds of other researchers have re-confirmed that work.

Competing interests: None declared