One sample, in fact, was negative for HN using the most sophisticated techniques available at the time. Yet workers in the laboratory were able to isolate a virus from the patient's blood. DNA "probes" (short pieces of DNA from the HIV genome) were then prepared. If the new virus were closely related to the original AIDS agent, those probes would bind to its genetic material. As it turned out, there was little binding, and it became clear that the new isolate was not simply a strain of the original AIDS virus but a new virus designated HN-2. Soon a second example was isolated by workers at the Claude Bernard Hospital; many others followed.
In evolutionary terms HIV-2 is clearly related to HIV-1, the virus responsible for the main AIDS epidemic. The two viruses are similar in their overall structure and both can cause AIDS, although the pathogenic potential of HN-2 is not as well established as that of the first AIDS virus. HN-2 is found mainly in West Africa, whereas HN-1 is concentrated in central Africa and other regions of the world. The finding of HIV-2 suggests that other undiscovered HIVs may exist, filling out a spectrum of related pathogens.
The isolation of HN-2 immediately raises the question of the evolutionary origins of these viruses. Although the answer to that question has not been found, some hints have been provided by the discovery in other primate species of related viruses called simian immunodeficiency viruses (SN's). The first such virus, found in the macaque monkey, is designated SN macaque. Isolated and characterized by Ronald C. Desrosiers and his co-workers at the New England Regional Primate Research Center in collaboration with Essex and his colleague Phyllis Kanki, SN macaque has been shown to be closely related to HIV-2, raising the possibility that HIV-2 may have come into human beings relatively recently from another primate species.
No such close simian relative has been found for HN-1 (although the right group of primates may not yet have been studied in sufficient detail). Hence the origin of HN-1 remains more mysterious than the origin of its relative HN-2. It is likely, however, that HN-1 has been in human beings for some time. One of us (Gallo), with Temin, has used the divergence among HN strains and the virus's probable rate of mutation to estimate how long the virus has infected people. It was tentatively concluded that HN has infected human beings for more than 20 years but less than 100, an estimate compatible with those by other workers and with our knowledge of the epidemic.
Where was HN hiding all those years, and why are we only now experiencing an epidemic? Both of us think the answer is that the virus has been present in small, isolated groups in central Africa or elsewhere for many years. In such groups the spread of HN might have been quite limited and the groups themselves may have had little contact with the outside world. As a result the virus could have been contained for decades.
That pattern may have been altered when the way of life in central Africa began to change. People migrating from remote areas to urban centers no doubt brought HN with them. Sexual mores in the city were different from what they had been in the village, and blood transfusions were commoner. Consequently HN may have spread freely. Once a pool of infected people had been established, transport networks and the generalized exchange of blood products would have carried it to every corner of the world. What had been remote and rare became global and common.
What weapons are available against this scourge? Perhaps the best weapon is knowledge. One key form of knowledge is a deeper understanding of HN, its life cycle and the mechanisms by which it causes disease. Although HN kills T4 cells directly, it has become clear that the direct killing of those cells is not sufficient to explain the depletion seen in AIDS. Indirect mechanisms must also be at work. What are they?
Many possibilities have been suggested. Infection by HIV can cause infected and uninfected cells to fuse into giant cells called syncytia, which are not functional. Autoimmune responses, in which the immune system attacks the body's own tissues, may also be at work. What is more, HIV infected cells may send out protein signals that weaken or destroy other cells of the immune system. In addition HN is fragile, and as the virus particle leaves its host cell, a molecule called gp120 frequently falls off the virus's outer coat. As Dani P. Bolognesi of the Duke University Medical Center and his co-workers have shown, gp120 can bind to the CD4 molecules of uninfected cells. When that complex is recognized by the immune system, cells thus marked may be destroyed.
That list does not exhaust the possibilities. One of us (Montagnier) is exploring the possibility that the binding of the virus to its target cells triggers the release of enzymes called proteases. Proteases digest proteins, and if they were released in abnormal quantities, they might weaken white blood cells and shorten their lives. The various proposed mechanisms are not exclusive, and several may operate at once. Yet one is probably central, and some of the most significant work on AIDS is that of distinguishing the central mechanism from the peripheral ones that accompany it.
Although it is clear that a large enough dose of the right strain of HN can cause AIDS on its own, cofactors can clearly influence the progression of the disease. People whose immune systems are weakened before HN infection may progress toward AIDS more quickly than others; stimulation of the immune system in response to later infections may also hasten disease progression.
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Add CommentEarly on ciclosporin was used to try and save Rock Hudson just before he died. The Doctors treating him apparently thought what was happening to the immune system resembled rejection or allergic response to self.
Reply | Report Abuse | Link to thisThe response apparently was dramatic. His t-cells skyrocketed in #.
He was too far gone though, for he died very shortly thereafter, and this line of reasoning on how to treat the then unknown viral infection was dropped in favor of pursuing angles the medical establishment favored.
Medical research like all science can be rigid when it comes to trying something new, and trying to re-imagine HIV as a virally induced allergy for experimental treatment's sake just goes against the ingrained accepted notions on what HIV is and how to treat it.
Everything is focused on finding a way to eradicate it from the system or limit its ability to reproduce or a vaccine.
While there were a few incidences of experimentation with ciclosporin beyond Hudson, all were dropped when the patient died. It was considered a "what do you have to lose" option.
Unfortunately, for some odd reason, because ciclosporin did not produce a miracle interested disappeared.
It never was tried in a proper setting where the patients were NOT at death's door, despite evidence that when tried on close to death patients the effects on the immune system was dramatic showing a marked transient jump in T-cells.
Ciclosporin deserves its day in the sun.
Perhaps it can modulate the overactive immune system downward enough so that T-helper cells don't go killing each other confusing each other with HIV, because HIV's coating is a product of the T-Cell outer envelope.
Once slowed down by ciclosporin perhaps the immune system would be more able to appropriately distinguish infected from healthy and properly manage the infection - turning it into a mild chronic infection rather than the killer it still is in many areas.
Of course, the biggest obstacle to even trying this is that ciclosporin is not going to make the big bucks the new anti-virals are, so its in the interest of big pharma to ignore it entirely no matter how positive the evidence is that such medications could play a successful role in managing the HIV infection.