Wednesday, January 9, 2008

280)No.6, 'Ayats'(Signs) in the Universe series. HIV/AIDS: Marvel of creation, foe of man.

41)No.6, 'Ayats'(Signs) in the Universe series. HIV/AIDS: Marvel of creation, foe of man.

Ayats(Signs) in the Universe series, no. 6HIV/AIDS: marvel of creation, foe of man.

August 2006. The upcoming world conference on HIV/Aids to be held in Toronto in a few days and attended by 26000 scientists has induced me to change the topic of item number 6 in my 'Ayats(Signs) in the Universe series' from one about life in strange places on earth to one about the molecular and cellular life cycle of the HIV/Aids virus and the sleuthing game scientists play trying to slow and shut it down. In order to even begin the process of taming this virus, we first had to delineate in excruciating detail the sequential unfolding of its activity from the time it tries to enter a human cell to the time a newly made virus leaves the cell in droves to infect other human cells. An essential part of this unfolding involved knowing the exact structure of this virus from the inside out(its morphology). Knowing the steps the virus takes from start to finish enables scientists to propose places in this sequence where one can block the virus's relentless and single-minded purpose which, from the virus's point of view, is to commandeer the human cell's apparatus and use it to produce many new viruses in its quest to propagate in a hostile world.

A virus is not a living organism like a bacteria or a human cell are. It is essentially a piece of genetic material around which is wrapped a few proteins that make up and stick out of its outer protective coat. It has no other organelles with which to produce energy or make and store essential molecules like sugars, proteins, fats and others.The only way a virus can propagate itself and its genetic material is to take over an autonomous living cell and use the cell's machinery to make new and more virus particles.

In his 'Memoirs', our 48th Imam made the following statement: "Islamic doctrine goes further than the other great religions, for it proclaims the presence of the soul, perhaps minute but nevertheless existing in an embryonic state, in all existence in matter, in animals, trees, and space itself. Every individual, every molecule, every atom has its own spiritual relationship with the All-Powerful Soul of God."

I wonder what the All-Powerful Soul of God had in mind in its great design of the universe when it created viruses. Viruses are not living organisms by the conventional definition of a living organism but they are ubiquitous in nature and can lay dormant for decades, even centuries, before they occasionaly make their virulent appearance. Could it be that dietary prohibitions in those other great Ayats(Signs), the Religious Scriptures, are to be taken seriously because they come from the same source of Wisdom that fashioned the 'Ayats'(Signs) of the Universe in the first place?

Carolyn Abraham of the Globe and Mail says:

"The closest ancestor of the AIDS virus lived in West Africa's chimpanzees for thousands of years, and chimps have long been on the menu of human hunters in that corner of the world.

Our guess would be that these viruses have been jumping from chimps into humans on countless occasions in the past," said Paul Sharp of the University of Nottingham, a leading expert on HIV's evolution. "But most of them don't make it to be an epidemic. In fact, until recently, none of them had made it out of rural areas or infected enough people to be noticed.

HIV is believed to have been killing people in Africa for roughly 50 years before the world knew the virus existed. Yet scientists have since discovered the pandemic virus was one of three types of HIV that jumped to humans around the same time. But due to a fateful confluence of events and genetic accidents, only the one — HIV-1, group M — gave rise to the global scourge that continues to stump medical science."

HIV begins its infection of a susceptible host cell by binding to a protein receptor( called CD4 ) on the host cell. CD4 is present on the surface of many lymphocytes, which are a critical part of the body's immune system. Recent evidence indicates that a coreceptor is needed for HIV to enter the cell. This recognition of HIV coreceptors and progress in understanding how HIV fuses with the cell has opened up new possibilities for antiviral drugs. Medical science has seized on this possibility. A number of new agents are being designed to prevent infection by blocking fusion of HIV with its host cell.

Following fusion of the virus with the host cell, HIV enters the cell. The most usual way that genetic information travels inside a cell is that DNA information is copied or transcribed onto an RNA molecule, which then leaves the nucleus to go into the main part of the cell, where the RNA codes for proteins by a process called translation. This is called the central dogma. The HIV bucks the trend of the central dogma because its main genetic molecule is RNA, not DNA. The genetic material of the virus, which is RNA, is released and undergoes reverse transcription into DNA. An enzyme in HIV called reverse transcriptase is necessary to catalyze this conversion of viral RNA into DNA. Inhibitors of reverse transcriptase, such as AZT, were the first anti-HIV medications, and are still a critical part of treating patients who have HIV.

Once the genetic material of HIV has been changed into DNA, this viral DNA enters the host cell nucleus where it can be integrated into the genetic material of the cell. The enzyme integrase catalyzes this process, and inhibitors of integrase are under study as a new way to block HIV replication. Once the viral DNA is integrated into the genetic material of the host, it is possible that HIV may persist in a latent state for many years. This ability of HIV to persist in certain latently infected cells is the major barrier to eradication or cure of HIV. For this reason, based on our current knowledge, patients must remain on anti-viral therapy for life.

Activation of the host cells results in the transcription of viral DNA into messenger RNA (mRNA), which is then translated into viral proteins. The new viral RNA forms the genetic material of the next generation of viruses. The viral RNA and viral proteins assemble at the cell membrane into a new virus. Amongst the viral proteins is HIV protease, which is required to process other HIV proteins into their functional forms. Protease inhibitors, one of the most potent types of anti-viral medications, act by blocking this critical maturation step. Following assembly at the cell surface, the virus then buds forth from the cell and is released to infect another cell.

Unless the HIV lifecycle is interrupted by treatment, the virus infection spreads throughout the body and results in the destruction of the body's immune system. With current anti-viral medications, such as reverse transcriptase inhibitors and protease inhibitors, HIV infection can be contained. However, a great deal more must be achieved before AIDS epidemic is brought under control. One important immediate goal is to design new, more potent medications that are easier to take and have fewer side effects. However, the ultimate challenges are to use our understanding of the HIV lifecycle to develop medications that will eradicate HIV from people who are already infected and to create a vaccine that will prevent new infections in the future.

Current medical science, therefore, has created and is creating drugs that block the HIV lifecycle at certin key points. The first is before the virus even can enter the cell and blocks the binding of the virus to the essential co-receptor that allows the HIV to fuse with the cell membrane and get inside the cell. This drug is still under development. The second is to block the step where the enzyme called reverse transcriptase changes the viral RNA to DNA, allowing it to match the cell's DNA and intergrate with it. A drug called AZT, which was the first treatment ever developed for HIV in 1987, blocks this enzyme that promotes this reaction. The third is to block another enzyme, called intergrase, that allows the viral DNA to intergrate with the human DNA in the lymphocyte. This is a hot area of research and a Toronto researcher will announce this week a new drug he has developed that blocks the enzyme intergrase. The fourth and final is a viral protein called HIV protease, which processes the proteins in the newly made virus into their functional forms, allowing the virus to leave the cell and infect other cells. Drugs called protease inhibitors are already in use to prevent the virus from becoming fully functional as it prepares to leave the cell to create havoc elsewhere in the body. Currently, the mainstay of treatment of HIV infections are a cocktail of AZT and these protease inhibitors, which have taken HIV and turned it from a sure death sentence to one where the disease can be controlled, provided one can afford the expensive medication.

Article in today's Globe and Mail about the International AIDS Conference being held in Toronto this week. This article highlights the new drug, called an intergrase enzyme inhibitor, which blocks the advance of the virus by preventing the viral DNA from linking up and intergrating with the DNA in the human immune cell:


The Qur'an itself repeatedly recommends Muslims to become better educated in order better to understand God's creation: Aga Khan IV(2007)
The Quran tells us that signs of Allah's Sovereignty are found in the contemplation of His Creation: Aga Khan IV(2007)
This notion of the capacity of the human intellect to understand and to admire the creation of Allah will bring you happiness in your everyday lives: Aga Khan IV(2007)
Islam, eminently logical, placing the greatest emphasis on knowledge, purports to understand God's creation: Aga Khan IV(2006)