Human immunodeficiency virus

Human Immunodeficiency Virus Greg Towers, Serious Science

Translation: Post-science

HIV is the first human retrovirus. A retrovirus is a special type of virus. It was known about it that it exists in other species, and HIV is the first example of such a virus in humans. HIV was first discovered in the early 1980s, when there were several cases of homosexuals turning to emergency departments in hospitals with a new disease, which apparently had something to do with immunodeficiency. Their immune system stopped working, and it was unclear why. It took some time to realize that it was a new viral infection that had not been observed in people before. It was first described in the early 1980s in San Francisco, and then scientists realized that it is much more widespread. The people who identified it worked at the Pasteur Institute: Francoise Barre-Sinoussi and Luc Montagnier worked in the laboratory on other retroviruses and discovered a retrovirus under an electron microscope in the cells of patients suffering from this infection.

They received the Nobel Prize for this work, and researchers from the USA, for example Robert Gallo, also made a great contribution to it. A test was developed to diagnose this virus, we learned how to diagnose the presence of this virus, and it turned out that a large number of people were infected with it, but there was no treatment at that time. And it turned out that the virus spreads through sexual contact, that is, it is a sexually transmitted disease, as well as through blood preparations, and at that time people who were injected with blood preparations, for example people with hemophilia, could have been infected with this virus. It is also possible to get infected, for example, through contact with blood – thus, injecting drug users are at risk: among them it often happens that several people use the same needle, and if one of them was infected, then everyone else who used the same needle will be infected. So in those days it was all very scary: a brand new virus appeared, people were dying, and no one knew what to do. But, fortunately, we knew quite a lot about retroviruses, because we conducted studies of retroviruses in other species, in particular in mice, so a new type of drugs for the treatment of HIV was developed quite quickly, and they are still used today.

By 2016, it is already possible to treat HIV with a cocktail of antiviral drugs, which in theory should prevent infection of new body cells. This means that the virus in most cases becomes impossible to detect, and we think that the patient can live a long enough life if he takes antiretroviral drugs. So if you can afford them, then everything is fine, and everything is fine in the West, but in resource-poor regions such as Tropical Africa, where there is less money and it is more difficult to buy quite expensive antiretroviral drugs, this is problematic. But they are available, and now there are extensive programs for the distribution of antiretroviral therapy so that every patient can get access to the necessary drugs.

HIV is a human retrovirus, it stands for "human immunodeficiency virus". There are several types of it, the most common is called HIV-1. AIDS – acquired immunodeficiency syndrome – is a disease caused by HIV. As far as we can tell, almost everyone who is infected with the virus eventually gets AIDS – it is very rare that people do not get sick, and it is very difficult to say whether an infected person will get sick: he may die earlier for some other reason. However, most of the infected suffer from this disease, but it does not develop earlier than 8-10 years after infection. So there is a long period of time when infected people do not suffer from significant symptoms, although there are still some symptoms.

When you first catch HIV, you get an infectious syndrome very similar to other viral infections, such as the flu. Then the virus replicates in your body to very high titers, that is, a very large amount of virus in the body, and you feel very sick. You may develop a rash and fever, and you may spend a few days in bed and feel as if you have picked up some kind of viral infection. And then everything goes away, your immune system suppresses the replication of the virus and can even suppress it to a very low level, such that a few weeks after infection, the virus in your body cannot be detected.

What happens next is not entirely clear, but it is known for sure that your immune system is constantly fighting the virus. During this period of time, you do not feel any special symptoms, so there is a feeling that you have become better, you have recovered, but in the case of HIV, this is not the case. It is still replicated in your body, which means that over time, for reasons that we don't fully understand, your immune system becomes depleted and stops working. At this moment, the virus takes over and destroys your immune system, and this whole long battle between the virus and the immune system ends with the complete defeat of the latter. Because of this, you get sick, and diseases caused by HIV are mostly opportunistic infections.

So all these are diseases that you don't usually suffer from, such as fungal infections. We are constantly being attacked by fungi that are trying to destroy us, but they do not succeed, because our immune system protects us. But without it, these fungal infections begin to cause very severe diseases of the mouth, lungs and respiratory tract. And by the time AIDS was discovered, all these diseases had not been observed in people before, because our immune system copes with them very well, so it was very difficult to treat them. Now different methods of treatment have been developed for these diseases. But until then, a long period of time must pass, about 8-10 years, during which your body fights the virus and keeps it under control.

Now it is believed that if you are infected with HIV, then you need to start medication as soon as possible, although earlier, if we saw that you were not suffering from any symptoms, we thought that there was no need to take drugs until the symptoms manifested. Now we can measure the number of CD4 cells that are the target of the virus, and we can monitor how your immune system is feeling. Previously, we started treating people only when they reached a certain point, after which their immune system failed. Now we believe that the earlier you start treatment, the better, as it helps protect your immune system from the damage it will take on itself, even while you yourself are not suffering from any serious symptoms. So the goal of modern therapy is to prevent the virus from multiplying. But this, unfortunately, does not lead to a cure, and we do not fully understand why. So if you take antiretroviral drugs, then you can suppress the replication of the virus to such a state that it will be invisible: it will be impossible to detect it in your body. But still, if you stop taking the drug, in a short period of time – about a few months – the virus will return. So we know that drugs don't completely get rid of the virus and the immune system can't get rid of the virus either, but we don't understand why.

I think there are two explanations, and a lot of research is currently being done in an attempt to figure out which one is true (or maybe both are true). The first explanation is that the virus is still in your body somewhere in the organs (possibly in the lymphoid tissue of the digestive system) and quietly reproduces itself there. The second explanation is that it really stops replicating, and the drugs allow you to get rid of all the cells that produce the virus. In this case, only those cells that contain the virus remain in the body, but do not actively produce it, so until they start producing the virus, it will not be possible to get rid of them. Therefore, if you stop taking the drugs, sooner or later these cells will start producing the virus, and everything will start all over again. So we don't fully understand whether we need to improve drugs to destroy the virus, including its remnants in the body, or whether we need a strategy to awaken cells that contain the virus, but do not produce it, in order to destroy them too. And this sets the agenda for research, the purpose of which is to find the best way to cure people to the end.

There are two large areas of HIV research. In the USA, it seems to me, they are now trying to focus all research on finding a cure. There is a feeling that we should not fool around, but just focus on treating patients, and this is the only way to eradicate the disease. Of course, there are also attempts to invent a vaccine, but we don't understand how to make it, and we don't know enough about vaccines to understand why we can't make an HIV vaccine. We've tried classic ways to get a vaccine, and they all just don't work with HIV. There are many possible reasons why this is so, but we don't fully understand them. And I don't think anyone believes that a vaccine will appear in the near future, so it seems to me that there has been a shift towards the idea that we need to look for new ways of treatment, perhaps with new therapy strategies. This is one area of research.

The second global area of HIV research is the use of HIV as a tool. HIV is a very small virus, it consists of nine genes – these are nine proteins. Some of these proteins are quite complex and can be broken down into several more, but still it is a simple virus. For comparison, the herpes virus consists of more than two hundred genes, whereas HIV has only nine. And because of this, HIV becomes a very easily controlled genetic tool.

We can use this virus to study cell biology, and it turned out to be a very powerful tool for understanding what happens in the cells of our body, how they work, how they divide, how matter moves, how they are organized, and HIV is an amazing tool in this field. For example, we have learned a lot about the export of RNA from the cell nucleus, how the export of RNA from the nucleus is regulated, how splicing is regulated. HIV has to manage these processes, and by studying how it does this, we have learned a lot about it. We have understood a lot about transcription control: HIV has its own transcription activator, but it does not work like other activators, and studying this process has allowed us to understand a lot about how transcription works in general. So this is an amazing tool for solving various scientific issues, and in my laboratory we use HIV precisely as a tool for studying the immune system.

I think there are two explanations, and a lot of research is currently being done in an attempt to figure out which one is true (or maybe both are true). The first explanation is that the virus is still in your body somewhere in the organs (possibly in the lymphoid tissue of the digestive system) and quietly reproduces itself there. The second explanation is that it really stops replicating, and the drugs allow you to get rid of all the cells that produce the virus. In this case, only those cells that contain the virus remain in the body, but do not actively produce it, so until they start producing the virus, it will not be possible to get rid of them. Therefore, if you stop taking the drugs, sooner or later these cells will start producing the virus, and everything will start all over again. So we don't fully understand whether we need to improve drugs to destroy the virus, including its remnants in the body, or whether we need a strategy to awaken cells that contain the virus, but do not produce it, in order to destroy them too. And this sets the agenda for research, the purpose of which is to find the best way to cure people to the end.

There are two large areas of HIV research. In the USA, it seems to me, they are now trying to focus all research on finding a cure. There is a feeling that we should not fool around, but just focus on treating patients, and this is the only way to eradicate the disease. Of course, there are also attempts to invent a vaccine, but we don't understand how to make it, and we don't know enough about vaccines to understand why we can't make an HIV vaccine. We've tried classic ways to get a vaccine, and they all just don't work with HIV. There are many possible reasons why this is so, but we don't fully understand them. And I don't think anyone believes that a vaccine will appear in the near future, so it seems to me that there has been a shift towards the idea that we need to look for new ways of treatment, perhaps with new therapy strategies. This is one area of research.

The second global area of HIV research is the use of HIV as a tool. HIV is a very small virus, it consists of nine genes – these are nine proteins. Some of these proteins are quite complex and can be broken down into several more, but still it is a simple virus. For comparison, the herpes virus consists of more than two hundred genes, whereas HIV has only nine. And because of this, HIV becomes a very easily controlled genetic tool.

We can use this virus to study cell biology, and it turned out to be a very powerful tool for understanding what happens in the cells of our body, how they work, how they divide, how matter moves, how they are organized, and HIV is an amazing tool in this field. For example, we have learned a lot about the export of RNA from the cell nucleus, how the export of RNA from the nucleus is regulated, how splicing is regulated. HIV has to manage these processes, and by studying how it does this, we have learned a lot about it. We have understood a lot about transcription control: HIV has its own transcription activator, but it does not work like other activators, and studying this process has allowed us to understand a lot about how transcription works in general. So this is an amazing tool for solving various scientific issues, and in my laboratory we use HIV precisely as a tool for studying the immune system.

About the author:
Greg Towers – Professor of Molecular Virology, University College London; Head of Research Group, UCL Division of Infection and Immunity.

Portal "Eternal youth" http://vechnayamolodost.ru  08.02.2017