By Alberto Conti, University of York
It was 1981, when doctors in the US started noticing strange patterns across their patients: in Los Angeles, some started contracting Pneumocystis carinii pneumonia; while in New York, cases of Kaposi’s sarcoma suddenly went on the rise. Oddly, in both instances, young and previously healthy individuals were being affected by diseases found exclusively among patients with weakened immune systems.
Reports like these ones became more common every month, and the number of people killed by these diseases started to increase at a worrying rate. It was soon clear that something was spreading across the population, and it was doing it fast. However, scientists were puzzled: they had never seen something like this, and had no way to prevent its spread – let alone treat it.
The scientific community quickly turned its interest towards this growing menace. Soon, researchers started to learn about the spread and development of the disease. Whatever it was, it seemed to severely weaken the host’s immune response. This feature lead to what became the official name of the disease: AIDS (acquired immune deficiency syndrome), first used in 1982. Scientists also noticed that most infections occurred within defined groups of the population, such as gay man, patients receiving blood transfusions (like haemophiliacs) and intravenous drug users.
Figure 1: Marchers on a Gay Pride parade through Manhattan, New York City, 1983.
These hints allowed Dr Françoise Barré-Sinoussi, Dr Luc Montagnier and colleagues at the Pasteur Institute, and Dr Robert Gallo’s lab at the National Cancer Institute, to independently discover a retrovirus in AIDS-derived blood in 1983. This is a type of virus comprising RNA (DNA’s more unstable cousin) as its genetic material, and after its link to AIDS was confirmed, it received the name we all know today: human immunodeficiency virus, or HIV.
The race for finding a suitable treatment was on – and it was desperately needed: an estimated 2.4 million people worldwide were living with HIV just by 1985, a trend that was clearly on the rise. The urgency of the epidemic led to scientist testing existing drugs in the hope of finding a suitable candidate – something that occurred in 1985 with azidothymidine (AZT, for short).
A) Dr Luc Montagnier (left) and Dr Françoise Barré-Sinoussi (right) after receiving the Nobel Prize for medicine in 2008.
B) Electron microscopy of HIV budding an infected CD4 T-cell, a type of immune cell responsible of coordinating the immune system.
Surprisingly, AZT was a compound designed for fighting cancer, not viruses. Why would it be effective against HIV then? Well, both diseases have a common underlying objective: make DNA. Cancer requires cells to divide; while HIV needs to convert its RNA into DNA. This is an essential step in retrovirus life cycle, as it allows them to integrate their genetic material within the genes of our immune cells.
There is no need of extensive chemical knowledge to see the similarity between AZT and thymidine, one of the four letters in our DNA (Figure 3). In fact, they are so similar that not even the HIV reverse transcriptase (the machinery responsible for turning RNA into DNA) can distinguish them. This allows AZT to be introduced into a growing DNA chain, but prevents any DNA assembly after it.
Figure 3: Comparison between the chemical structures of thymidine and AZT.
This turned out to be a very efficient strategy – so efficient, in fact, that it only took 25 months for AZT to be released to the market (a process that generally takes over a decade!). However, despite its efficacy, HIV resistance quickly started to emerge. As the understanding of the disease increased, new drugs targeting different parts of the virus life cycle improved the treatment options, and in 1995, a highly active antiretroviral therapy (HAART), comprising a combination of drugs complementing AZT-like medication, was approved.
This certainly marked a turning point in the HIV epidemic, decreasing the number of new infections and HIV-related deaths, and making the disease more manageable. However, despite the advances made since the virus was first discovered, a definitive cure is yet to be discovered. It is fundamental to remember that many people still suffer from this disease, with 5,000 new infections occurring every day, and most of them in regions with limited access to treatment. For this reason, supporting the fight and research against HIV remains as vital as it was back in the 80’s.
I am a third-year undergraduate student at the University of York, currently in a placement year in GlaxoSmithKline. I work within the Immunoinflammation department, focusing on the role of dendritic cells in autoimmune diseases. When I’m not in the lab, I enjoy learning stuff like guitar or programming. I also play American Football, and frequently practise how to avoid getting tackled.
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