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HIV/AIDS – A Reminder That We Are Still Facing An Uphill Battle

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Author: Dr. Akash Bhattacharya | Category: Beyond The Bench | September 21, 2016

Dr. Akash Bhattacharya is a biophysics researcher who is working in Dr. Dmitri Ivanov's lab on fundamental HIV-host interactions which help fuel downstream drug discovery. Below, he explains seven important facts about HIV and AIDS. 

1. There are more than 36 million people infected with the Human Immunodeficiency Virus. This includes 2.6 million children. About 1.1 million people died from HIV/AIDS in 2015. This number has dropped from a peak of 2.2 million deaths in 2005. Better availability of antiretroviral medicines and increased awareness has helped matters, but the global community still faces a Herculean challenge in combating HIV/AIDS.

2. About 0.8 percent of the world’s adult population is currently infected by HIV. However, in the most seriously affected countries, such as Swaziland and Botswana – this number is a shocking 27 percent. Unfortunately, this high prevalence of HIV also correlates with weak public health infrastructure and precipitous drops in life expectancy, especially in the last 15 years. AIDS has claimed over 36 million lives so far.

3. HIV is a virus. A lot of adjectives can be applied to a virus – brutal, elegant, simple. But above all – efficient. A virus contains the bare minimum biological arsenal it needs to take over a host cell. Viruses do not have the requisite biological “equipment” to live complete life cycles (The viral equivalent of finish high school, go to college, get a job, etc) outside of a host cell. Thus viruses exist in that twilight zone between the living and the non-living.

4. More specifically, HIV is a retrovirus. Almost all of life appears to follow what is called the “Central Dogma of Molecular Biology.” In simple terms, DNA is the main repository of all the information that life processes need. DNA is transcribed into RNA, which is then translated into proteins. Proteins perform all the duties that keep each cell in you and me alive. Retroviruses, however – carry their information storage as RNA, not DNA. Once they have invaded a host cell, they reverse-transcribe this RNA into DNA – and then proceed to attach their DNA to the host cell’s DNA. The infected host cell has now been successfully colonized - when it now translates its DNA to make proteins, it will also be translating the viral DNA – and making proteins for the colonizing virus.

5. Even more specifically, HIV is a lentivirus, or a “slow” virus. Most retroviruses still face a challenge – how to access the host cell’s DNA. The host’s DNA is normally locked away secure in the cell’s nucleus. It is only during cell division that the nucleus falls apart and the host cell’s DNA is in the cytoplasm, vulnerable to viral attack. However, many cells – for instance T-cells of the immune system do not divide once they have matured. This is where lentiviruses shine. HIV has the ability to Mission-Impossible it’s genetic material into an intact host cell’s nucleus. Once it does so, infecting CD4 cells of the immune system – it has basically destroyed the human body’s ability to fight back. 

6. So how do we fight back? The answer is simple – we target every possible weakness of the virus and we use as many biochemical weapons as possible. This philosophy is embodied in modern HAART (highly active anti-retroviral therapy). Entry-inhibitors target the process of viral fusion with the host cell membrane. NRTIs and NNRTIs prevent the reverse-transcription of viral RNA into DNA. INSTIs prevent the virus from pasting its DNA into the host cell’s DNA. Finally, protease inhibitors act on the exit-and-release side of the viral life cycle.

7. However, the virus can and does fight back. The process of reverse transcribing viral RNA to DNA is very unlike the process of DNA replication – because the enzyme in charge lacks the ability to “proofread” its own work. Paradoxically, this sloppiness works in favor of the virus. This is because errors in reverse transcription lead to mutants. HIV is a rapidly changing virus – and by simple virtue of numbers – can form enough mutants that some of them will be successful in evading anti-retroviral drugs. This is Nature at its nihilistic extreme – brute numbers can, and frequently do win the day against the cleverest and most painstakingly designed drugs.

This, in a not-so-small nutshell is the motivation for the research that we do. Understanding how HIV works is not just of paramount importance from a global public health and economic point of view, but it is also a surpassingly beautiful intellectual challenge.

References and further reading:

The "Beyond The Bench" series features articles written by students and postdoctoral fellows at the Graduate School of Biomedical Sciences at The University of Texas Health Science Center San Antonio.

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