You may recall a flurry of media hoopla a month ago over some dramatic *disneyworld* images of "HIV" attacking a Tcell. These reports are more like the fuzzy footage supporting UFO sightings and either fall apart under scrutiny of are impossible to substantiate.

"The pictures of the virus that have appeared around the world are artists' impressions and computer simulations, based on indirect observations by molecular biologists, not isolation of the virus itself," points out Neville Hodgkinson.

Judge for yourself if they have really witnessed "an actual AIDS virus attacking a human cell".

SHOW: NPR TALK OF THE NATION (NPR 2:00 pm ET)
JUNE 19, 1998, FRIDAY
HEADLINE: AIDS Update
BYLINE: Ira Flatow, New York

[interviewed: John Moore, Senior Scientist, Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY]

extract:

FLATOW: Let's talk about this amazing picture, a literal picture, that came out yesterday in the journals, that showed an actual AIDS virus attacking a human cell, and why that is so important. Describe what we saw there.
MOORE: Well, what the groups at Columbia University and the Dana Farber in Boston have done is to take the GP-120 coat protein that the virus uses to bind to its cells and they've crystallized it, put it into a regular array and used x-rays to probe the structure and see how all the atoms fit together. And that tells you what the shape of the molecule is.
FLATOW: So there's a molecule on the outside of the AIDS virus...
MOORE: Yeah.
FLATOW: That's like a probe-looks for ways to attach to a human cell.
MOORE: Absolutely. It recognizes specific proteins on the human cell surface.
FLATOW: And they crystallize that little...
MOORE: They crystallize that viral coat protein.
FLATOW: That coat protein.
MOORE: Which is a technological tour de force, that groups have been trying to do for about a decade. And it's a wonderful scientific achievement.
FLATOW: So but they actually made a crystal out of it...like a sugar crystal you would make out of a...
MOORE: You can analogize it to a sugar cube, yeah.
FLATOW: And x-ray crystallography means they zapped it with x- rays to take a picture of it.

Some new papers (published in "Nature" vol 393, p.648 and p.705; "Science" vol 280, p.1949) describe how "HIV" can infect cells.
Does anybody know how these observations can be explained without a viral entity ?

Thanks,
Michael

**********Reappraising-AIDS Discussion Group**********

Michael, are you referring to this [NIH report below]? I haven't read these papers yet[meaning the references in the report], but I'll try to take a look at them. My initial impressions are:

1. This is a study of a protein crystal. Actually, it is not just one protein, it is 3 proteins in some sort of complex. The biggest problem for people who do x-ray crystallography is to actually obtain good crystals of what they are interested in. Often they spend years waiting for crystals to form, and usually they never get crystals. Because of this, they will mix their protein with many different things in different combinations, in the hope that one combination/mix will give them a crystal they can study.

2. Proteins do not exist in living systems as crystals, nor do any of their functions rely on a crystal structure. In reality, proteins can be thought of as vibrating, or at least having considerable flexibility as a molecule in solution. Also, their shapes may change depending on what molecules they are interacting with.

3. While x-ray crystallography did provide some of the key evidence for the structure of DNA, it has not been as useful in the study of proteins. The protein I study, for example, has a structure that is best described as "dumbell" shaped in its crystal form, but everyone in the field recognizes the limitations and artificial nature of this.

4. This latest hooplah will fall the way of all the rest. What ever happened to fusin, that protein that was so hyped a couple years ago? This was supposed to be a host protein that "HIV" interacted with as it "infected" a cell. When you have a faulty hypothesis, no matter how hard you hype a study, the results will never get you anywhere. All dead ends and contradictions in this field...

[Todd Miller]

**********Reappraising-AIDS Discussion Group**********

> Some new papers (published in "Nature" vol 393, p.648 and p.705; "Science" > vol 280, p.1949) describe how "HIV" can infect cells.
> Does anybody know how these observations can be explained without a viral > entity ?

This is just more of the same. They have a photo of entities that look like retroviruses in stimulated cutlures, and proteins from those cultures. They fool around with this soup, and assume that the results of their fooling around are explained by the existance of a virus. None of it matters, of course. If a virus does explain their fooling around, this virus is harmless and has nothing to do with why AIDS patients are sick.

-- Paul Philpott

"Reappraising AIDS", the monthly publication of The Group for the Scientific Reappraisal of the HIV/AIDS Hypothesis

Back issues, other info: http://www.wwnet.net/~philpott/ReappraisingAIDS

For one year subscription, send $25 check (USA), or $35 US cash (for non-USA)

to: 7514 Girard Ave #1-331/ La Jolla, California / 92037

**********Reappraising-AIDS Discussion Group**********

NATIONAL INSTITUTES OF HEALTH
National Institute of Allergy and
Infectious Diseases

EMBARGOED FOR RELEASE
Wednesday, June 17, 1998
2:00 PM Eastern Time
June Wyman
(301) 402-1663
jwyman@nih.gov
Crystal Structure of Key HIV Protein Reveals New Treatment Targets

In a finding that unlocks new doors to devising drugs and vaccines against HIV, scientists have crystallized the core of gp120, the surface protein molecule that the virus uses to attach itself to immune system cells.

The new model of the gp120 core's crystal structure reveals specific targets for anti-HIV vaccines and drugs, and highlights the surprising array of defenses that the virus uses to evade attack.

"Studying the gp120 crystal's structure can tell us a lot more about how the virus locks on to immune system cells," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "We now have specific target sites on which to focus in developing new drugs and vaccines."

The research, funded in part by NIAID, comes from a team led by Joseph G. Sodroski, M.D., of the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., and Wayne Hendrickson, Ph.D., of Columbia University College of Physicians and Surgeons, New York, N.Y. Their work appears in the June 18, 1998, issue of Nature and the June 19, 1998, issue of Science.

The scientists confirmed several previously known features but also found some surprises in the crystal structure of the protein. "We discovered that a large part of the gp120 surface is protected against attack by a dense array of carbohydrates and by an amazing capacity to change shape," says Dr. Sodroski.

Among their findings were:

•A shape-shifting device that allows gp120 to shield itself from antibodies until it reaches CD4 receptor sites on the immune system's T-cells - the first step in hijacking these cells. Loop-shaped projections that stick out above the molecule's surface hide the critical locking regions. When the virus reaches its target, the loops collapse and move out of the way, unmasking the locking regions.

•An icing of carbohydrate molecules that also shields the receptor-binding regions of the gp120 surface from antibody attacks. Finding a way around these molecules, or even removing them, would be another line of attack against the virus.

•A structure that gp120 uses to attach itself to CCR5, a co-receptor needed to bind CD4 sites on the host cell. Because this structure is stable and therefore vulnerable, it could be another useful target for drugs or vaccines.

•A large "silent face" - a surface that does not react to antibodies and is thus invisible to the immune system.

•A ball-and-socket interaction: a residue of phenylalanine 43 that sticks out from CD4 receptors and fits into a hole on the surface of gp120. This phenylalanine "stick" could be a focus for drugs to block the interaction.

•Several additional cavities in the surface of gp120 that could be exploited to block the molecule from binding to CD4 receptors.

The new information on gp120 structure suggests that some current approaches to AIDS vaccines may not work. For example, vaccines based on simple gp120 subunits may not get past gp120's ability to hide its critical binding regions until the last minute. At the same time, the crystal structure reveals vulnerable parts of gp120's architecture that researchers could hone in on to devise new drugs and better vaccine candidates.

"HIV is a viral Houdini," says Dr. Sodroski. "It carries a multiply protected infection machinery that frustrates host defenses. Understanding this machinery should help us target medical interventions to the weak spots in the armor."

The research was funded by NIAID; the National Institute of General Medical Sciences; the Howard Hughes Medical Institute; the American Foundation for AIDS Research; the Aaron Diamond Foundation; the G. Harold and Leila Y. Mathers Foundation; the Friends 10; William McCarty-Cooper; and Douglas and Judi Krupp.

NIAID supports biomedical research to prevent, diagnose and treat illnesses such as AIDS, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

, Press releases, fact sheets and other NIAID-related materials are available via the NIAID Web site at http://www.niaid.nih.gov.

References:

PD Kwong, et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:705-11 (1998).

R Wyatt, et al. The antigenic structure of the human immunodeficiency virus gp120 envelope glycoprotein. Nature 393:648-59 (1998).

C Rizzuto, et al. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280:1949-53 (1998).

TORONTO

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