Why antibody 3BNC117 is new hope for the treatment of HIV? –

HIV Virus (green) specializes in attacks on leucocytes (white) of the

This method is based on a neutral antibody called 3BNC117. Unknown 3BNC117 likely “search and destroy” HIV or not, but it prevents HIV from infecting new cells, white blood cells, particularly CD4 cells. Simply so, but why it is considered a promising?

HIV does not directly kill people!

First of all, we need to understand some basic information about HIV and why is it dangerous. HIV is byHuman Immunodeficiency Virus , also known as virus that weakens the immune system in humans. Ie this virus attacks the immune system. Together with HIV type SIV ( Simian immunodeficiency virus ) also weakens the immune system, but only attacks on other primates-humans. Many researchers believe that HIV is a subsidiary of SIV mutants, in which SIV CPZ (or chimp chimpanzee) is seen as a bridge between SIV and HIV.

The white blood cells (yellow) is “eating” bacteria (orange)

In fact, HIV itself is not fatal, but it is the target of the immune system ( immune system ). So while the number of white blood cells decline, it facilitates other pathogens attack the human body (which it is not possible before the immune system is stronger), leading to the body depleted and eventual death syndrome (AIDS). This is similar to the human society, if the police are working effectively to suppress crime, society will be safe. However, if there is only one volume crime attacks on police, prompting police weakened, other crimes conditional “Rise” and society becomes unstable. HIV main danger in that place – attacked the system “policing” the only human.

Thus, people infected with HIV do not die after just a few months or weeks as rabies virus, flu, Ebola … but usually after 9-11 years, when the immune system has been depleted. This number may change if the body was weak infected available for different types of the disease before it.

How it works HIV

Similar to other viruses, HIV and reproductive infection by parasitic forms of cells. When HIV approaches leukemia cells (such as macrophages and CD4), the first link ( binding ) protein gp120 and gp41 including 2 will seek to integrate into the next point ( receptor ) on CD4 cell membrane. When this link is created, the CD4 protein changes shape, allowing the gp120 access to a further point is that CCR5. At gp120 “unlock” CCR5, white blood cell membrane and the outer virus will mix together to help bring HIV’s genetic information (RNA) into the cell.

Structure of an HIV

But the RNA of HIV will not do white blood cells if it is not reverse transcription ( reverse transcript ) into DNA. This process occurs by an enzyme RT ( reverse transcriptase ) which is available inside the virus and are “attached” with RNA of HIV. This enzyme is specific to retroviruses group with “Style” reverse transcription of RNA into DNA, which HIV is one of them. RT enzyme was “dangerous” in that it turns a single RNA sequence of a DNA double chain, making the “fake” complete than ever.

The glycoprotein of HIV from entering white blood cells through the CD4 and CCR5 portal

After DNA “spy” was created, from the moment it can penetrate the cell nucleus and the “hidden” part of the DNA of a cell. This process is again “help” by enzyme IN ( Integrase ) also available in HIV. Enzyme would “cut” DNA of stem cells and “insert” DNA “spies” in the middle, later “glued” to make things “like new”.

The panorama of the life cycle of HIV from intrusion until reconstructed

Basically, this step to the ultimate goal of complete HIV. From here, everything happens automatically when the white blood cells “live and work” just like other cells. It will translational ( translate ) DNA in the cell nucleus (already infected) to synthesize proteins that are essential ingredients for a new virus. It will also transcribed ( transcript ) to make new DNA into RNA. RNA, which is then combined with new materials and new viruses on the birth, continuation “career” and spread the infection.

The mischief of HIV

The process of HIV infection on not only the scientists said. In fact, the immune system of humans “known” to them before most. The change of the macrophage cells as well as the disappearance of CD4 cells are the body people realize. Of course, the immune system will try to deal with this pathogen. But why they failed?

“Relatives” of HIV, SIV, which infects only with other primates, also infect the same form. SIV is believed to have existed for at least 32,000 years ago before. With time so short-lived and the life “better” by many species of monkeys, apes … they are all supposed to have been extinct. But on the contrary, they are all still alive and well “flood”. The study showed that although the body of primates on the amount of SIV are quite high, but they are not blown AIDS in humans. Why?

Chart genetic relationship between SIV and HIV

There are two reasons set forth. One is that the immune system of the species has “learned” how to survive with SIV, they are not harmful to the host. Two of SIV is no “toxicity” as HIV – more precisely, the SIV did not have high mutation rates and short life cycle, such as HIV. On an average day, about 10 billion nascent HIV virus, with higher mutation rate – 10,000 times copying and reverse transcription is 3 times the original nucleotide (A, T, C, G) is changed . With such features, from an initial HIV-line, then there will be hundreds of HIV lines with different traits. That one must divide into groups of HIV ( group ), and even in group M (accounting for 90% of HIV cases), there came a dozen subgroups ( subtype ) is different.

Groups and subgroups of HIV on record

The very diverse HIV strains is caused not only scientists “embarrassment” to treat them that the human immune system and defeat the virus, “devious” is. Method of HIV activities outlined in fact just one of many ways of infection. HIV variants later “found” the positions of other proteins in the cell membrane to penetrate inside. Even when HIV was developed, in the same cells infected with HIV can survive multiple lines with a “break-in” different.

In addition, we also need to note further that HIV currently have 2 main types – HIV-1 and HIV-2. In which HIV-1 is the type that people often mention. As HIV-2 genetic, it is close to SIVmm than with HIV-1. HIV-2 in fact far more HIV-1 SIV CPZ (viewed as a bridge between SIV and HIV). HIV-2 was eventually causes AIDS, but a long time to happen than HIV-1 and it is relatively “benign” than the other brother. Due to lower-infectious HIV-1, HIV-2 is mainly concentrated in some West African countries rather widespread as HIV-1.

And new hope …

From the above, we can see HIV (or HIV-1) dangerous and difficult to treat in that they have very fast mutation rate. Ability mutations making them resistant after a period of treatment (which rows affected but will slow proliferation of new resistant strains continue growing rapidly). This is why until now, people still have not found a cure to HIV-1 treatment completely.

But as mentioned, the confrontation between HIV and the immune system is not just HIV own game. The body immune system also seeks to identify new HIV strains and destroy them. The only problem is the immune system often “slow step” before and after the body of HIV-blown AIDS.

Mutability of HIV thanks to Transcriptase enzyme with the ability to translate … “error” high

But the arms race is likely to have different outcomes …

Try to look back at the history of mankind through World War 2 (WW2). We all know the Germans failed after depletion of resources and not enough military power to confront the Soviet (Russian) on the eastern US and coalition troops on the west England. But until the end of the war, the Germans have invented the most important weapon that would most powers are used as jets, stealth aircraft, missiles, submarines engine power … At the Germans made them, the Allied nations are no real weapons to deal effectively.Allied victory for the Germans were exhausted to produce the series.

So what if the Germans made all things in the beginning instead of the end of the war WW2? Very likely the world today is very different …

The story of the immune system and HIV are similar. Antibodies 3BNC117 mentioned in the first article is the result “study” of the human immune system. On average, 10-30% of patients have developed antibodies after a period of being infected with HIV. Unfortunately, when the body of the patient, the extracts were 3BNC117 HIV strains in their “step one step ahead” …

But what if 3BNC117 present in the body from infection days?

According to research by Rockefeller University, 3BNC117 very strong effective approach to preventing HIV in CD4 position on the leukocyte membrane. If the virus does not penetrate the host cell, it will not regenerate and defeat the purpose of infection. Marina Caskey, co-author of 3BNC117 study, said: “The special thing about this type of antibodies is that they have an impact on the efficiency to 80% of HIV-line and we are very potential (for medicine)” .

3BNC117 prevent HIV with CD4 access ports on the cell membrane

Results Rockefeller University study shows 3BNC117 was “blocking” the spread of 195 out of 237 HIV-known line. In the series of experiments on the human body, at the highest dose (30 mg 3BNC117 / 1 kg patient), all patients showed a decreased amount of virus in the blood up to 300 times! Most patients reached the lowest virus is injected just after 1 week. The percentage decrease depending on the amount of virus are available as well as the number of lines affected the virus at the time before being injected.

Besides, not only have an impact 3BNC117 “acute” but also for “chronic” long. In some patients, even with a single injection, the effects of prolonged 3BNC117 continues. In half of the patients received the highest dose, the amount of virus in the blood has always been maintained at a lower level before injection during 8 weeks (when the experiment ended) and resistance 3BNC117 are not forthcoming. We can time before injection as soon HIV mutation higher efficiency.

In addition, this study also predicts the possibility of “search and destroy” the 3BNC117 HIV. Accordingly, 3BNC117 can penetrate the cells were infected before, which acts as the “barracks” trained HIV and kill them. Penetration is impossible for anti-retroviral drugs now. However, 3BNC117 capable “supernatural” aerial will need to be studied in more detail. If so, this is really a good news for all HIV research facility.

Of course, we should not rush to celebrate the news. In fact, the patient can make 3BNC117 finally died, so there is still 20% of HIV-line “escape”. However, let’s hope that they do not go in vain for the remaining part of humanity. So if HIV is detected as soon as, the number of them in the body is not high, and of course, the number of mutants will be no more. In the case of HIV has not mutated into the line “exit” 3BNC117 still capable treated (but patients with the mutant, we still had to replace them).

Instead of a conclusion …

3BNC117 or any other antiretroviral drugs, of course, are not sufficient to “suppress”, using only one type.We need to be able to incorporate a lot of different strains. Caskey said: “Only one type of antibody alone, and only one drug, will not be enough to oppress whole virus because after all, the resistance will appear” .

Hopefully one day people will soon be complete treatment of HIV / AIDS

Meanwhile, co-author, Florian Klein, 3BNC117 optimistic: “In contrast to retroviral therapy traditional antibody-based therapies which enables proactive approach to the infected cells, will give allowed to remove the virus from the body more efficiently “ .

The Rockefeller University researchers also hope to find a vaccine for HIV 3BNC117. Because in addition to medical uses, the 3BNC117 can play a preventive role. They hope that if any body can help people with HIV can not create 3BNC117 from the beginning, they have the ability to “dead keys” HIV virus before it can put the seeds in the body.

However, from now until the dream a reality, always carry condoms and avoid sharing needles types. After all, prevention is better than cure.

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