Author: Dr. Akash Bhattacharya | Category: Beyond The Bench | January 11, 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 35 million people infected
with the Human Immunodeficiency Virus. This includes 3.4 million children.
About 1.5 million people died from HIV/AIDS in 2013. 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
25 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:
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