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ISIS Report - March 22 2001

Genetic Engineering Superviruses II

Virologist in Yugoslavia warns against AIDS vaccines that can generate new viral and bacterial pathogens and trigger cancer, on account of a recombination hotspot in the AIDS viral gene. He intends to campaign against GM crops with the CaMV 35S promoter for the same reasons. Dr. Mae-Wan Ho reports

New viruses and bacteria from AIDS vaccines

There have been intensive efforts dedicated to developing a vaccine for AIDS, particularly in view of the raging AIDS pandemic worldwide. But there has been no success so far. On the contrary, Dr. Veljko Veljkovic, virologist in the Laboratory for Multidisciplinary Research, Institute of Nuclear Sciences in Belgrade,Yugoslavia, has been warning his fellow scientists against using many AIDS vaccines since 1990.

The vaccines on his hit-list include whole killed or attenuated AIDS virus, HIV-1, or SIV (the related virus from monkey), recombinant HIV proteins and peptides, recombinant viral and bacterial vectors expressing HIV proteins, and plasmids engineered with the HIV envelop glycoprotein gene.

It turns out that the envelop glycoprotein, gp120, of HIV-1 is similar to the region of human immunoglobulins involved in antigen-binding, a crucial step in the immune response. Thus, any AIDS vaccine containing the glycoprotein or the gene could strongly interfere with the immune system and make it more vulnerable to the virus. And in the long term, it could accelerate disease progression in HIV patients that do not yet have symptoms. Recombinant viruses expressing gp120 could also be a source of potential new pathogens.

The gp120 gene contains elements that stimulate recombination or are recombination hotspots. These elements are similar to certain Chi sequences found in bacteria and viruses such as Haemophilus influenzae, Mycobacterium tuberculosis, hepatitis B virus and herpes simplex virus that often co-infect with the HIV, and are also similar to Ig recombination elements in the human host. Recombination of HIV with bacteria and viruses mediated by Chi sequences would generate new pathogens. Within the human host, recombination with human genes would promote chromosomal rearrangements and the formation of aberrant immunoglobulins leading to inadequate immune responses. Furthermore, HIV-1 sequences integrated into the genome also act as retrotransposons, and have the potential for a wide variety of diverse genetic effects caused by all mobile genetic elements, especially mutations of genes due to random insertion, some of which might trigger cancer.

Using reverse transcriptase followed by polymerase chain reaction (RT-PCR), followed by DNA sequencing, Dr. Veljkovic's group, in collaboration with groups in UK, Italy and US, isolated HIV-1 viral sequences carrying the complete Chi recombination hotspot (GCTGGTGG) from the blood of three out of 11 AIDS patients. In one of the patients, recombination had occurred at this point with a gene from the bacterium, Haemophilus influenzae.

In fact, this is not the first time that recombination has been identified involving the AIDS virus. The authors suggest that such recombination may have been involved in a number of other cases reported in the literature. For example, an unusual form of the bacterium Mycoplasm fermentans found carrying part of the HIV-1 gene, has been implicated in the Gulf war syndrome (2). New subtypes of HIV-1 have arisen by recombination between HIV-1 subtypes. The HI.V-1 subtype N, which is distinct from other known subtypes but very close to the chimpanzee immunodeficiency virus, could have resulted from recombination between HIV-1 and SIV (3). They also suggest that the HIV-1 envelope gene could interact with human oncogenes that have Chi sequences.

They conclude:

"These results strongly support and reinforce our previous contention and the serious concern that AIDS vaccine candidates carrying the HIV-1 env gene on viral and bacterial vectors, could result in the generation of new pathogens with unpredictable effects on the immune system." (p.1462)

"...despite the urgent need for preventive AIDS vaccines, it would be wise to introduce a moratorium on clinical trials until there is a serious reexamination of the current concepts for their development."(p.1466)

The lesson for CaMV 35S promoter

Some people may be aware of ISIS' campaign to get GM crops with CaMV 35S promoter withdrawn from all environmental releases mainly because the promoter has a recombination hotspot with all the potential hazards that Veljkovic's group has described (4-7, also available on ISIS website <www.i-sis.org.uk>).

I received an e-mail message from Dr. Veljkovic on March 11, 2001 regarding the CaMV 35S promoter,

"As a consequence of the past war our country is heavily contaminated with different

pollutants ranging from toxic organic substances to depleted uranium. For this reason we are expecting increase of frequency of different chronic diseases most of which could be consequence of the genomic instability induced by pollution.

"Introduction of a large amount of the GM soy containing an inherently recombinogenic element in such vulnerable population represents an additional risk. I would like to point out another possible problem with CaMV promoter. We have demonstrated that Chi recombination hot spot is responsible for in vivo recombination between HIV and bacteria H. influenzae ... On the other hand, the prion gene contains repeats of this recombination promoter. It will be interesting to see consequences of possible interaction between these two recombination hot spots (Chi and CaMV) after massive substitution of the bone-meal by the GM cattle-food."

And again on March 15,

"There are some reported results indicating that genetically related retrotransposons among phylogenetically unrelated hosts can be transferred horizontally. The Ty1-like retroelement from soybean (SIRE-1), encoding a retroviral env-like protein, represents such an element. Taking into account this fact and presence of recombination hot-spot in the form of the CaMV promoter it is reasonable to expect problems with GM soy which will be imported here next month."

Dr. Veljkovic tells me that he will start a campaign against the import.

I am very grateful to Dr. Veljkovic for drawing our attention to his important work.

1. Prljic J, Veljkovic N, doliana %, Colombatti A, Johnson E, Metlas R. and Veljkovic V. Identificaion of an act9ive Chi recombinational hot spot within the HIV-1 envelope gene: consequences for development of AIDS vaccine. Vaccine 1999: 17: 1462-7.

2. Nicolson GL, Nicolosn NL and Nasralla M.Mycoplasmal infections and fibromyalgia/chronic fatigue illness (Gulf War Illness) associated with deployment to operation Desert Storm. Int. J. Med. 1998: 1: 80-92.

3. Simo F, Mauclere P, Roques P, Muler-Trutwin MC, Saragosti S, Georges-Courbot MC, Barre-sinoussi F and Brun-Verzinet F. Identification of a new human immunodeficiency virus type I distinct from group M and group O. Nature Med. 1998: 4: 1032-7.

4. Ho MW, Ryan A. and Cummins J. The cauliflower mosaic viral promoter - a recipe for disaster? Microbial Ecology in Health and Disease 1999: 11: 194-197.

5. Cummins J, Ho MW and Ryan A. Hazards of CaMV promoter. Nature Biotechnology 2000: 18: 363.

6. Ho MW, Ryan A and Cummins J. Hazards of transgenic plants with the cauliflower mosaic viral promoter. Microbial Ecology in Health and Disease 2000: 12: 6-11.

7. Ho MW, Ryan A and Cummins J. CaMV 35S promoter fragmentation hotspot confirmed, and it is active in animals. Microbial Ecology in Health and Disease 2000: (in press).

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