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▎The content team editor of WuXi AppTec "Let’s get married and stay alive.
Even after half a year or half a month, we are also husbands and wives.
When we die, we can be buried together upright, and we are also a home.
" "The Most" starring Aaron Kwok and Zhang Ziyi "Love" once made a lot of tears, because all the villages selling blood are AIDS patients, and all the villagers can do is bury each other and wait for death.
In the eyes of many people, "AIDS" and "terminally ill" are equated, but there is a small group of lucky people who successfully healed themselves or were cured.
Image source: 123RF "Berlin patient"-the world's first AIDS cured In 1995, American Timothy Ray Brown was diagnosed with HIV infection in Berlin, Germany, and was therefore called "Berlin patient" ".
To make matters worse, in 2007, he suffered from a blood cancer called acute myeloid leukemia (acute myeloid leukemia), so Timsey received a bone marrow transplant from a person with natural resistance to HIV.
The person who donated the bone marrow to Timsey happened to have a rare genetic mutation in a gene called CCR5.
There is a class of leukocyte chemotactic factors (chemokines) and corresponding cell receptors in the human body, which are involved in the immune regulation of leukocytes and lymphocytes.
The Chinese name of CCR5 is chemokine receptor 5, which is a protein receptor on the surface of white blood cells.
The CCR5 gene encodes this protein.
HIV specifically attacks CD4-positive lymphocytes in the human body, proliferates in the lymphocytes, destroys the lymphocytes, and causes cell lysis, thereby continuing to infect and destroy other lymphocytes.
Therefore, AIDS is also called Acquired Immunodeficiency Syndrome.As early as 1996, researchers discovered that in addition to CD4, CCR5 is one of the two co-receptors for HIV to enter cells.
Certain HIV strains need to bind to CCR5 on the cell surface to enter lymphocytes.
The CCR5 gene mutation is equivalent to locking the door, making people with this gene mutation resistant to HIV infection.
▲HIV invading lymphocytes need to bind to the CD4 and CCR5 receptors on the cell surface (Image source: US National Institutes of Health-National Institute of Allergy and Infectious Diseases, Public domain, via Wikimedia Commons) After receiving a bone marrow transplant, Timsey's body The newly generated lymphocytes all carry mutations in the CCR5 gene.
Therefore, HIV cannot enter its lymphocytes and cannot survive in the human body.
Three months after the operation, Timsey could no longer detect HIV in his blood.
He thus became the first AIDS patient in the world to be cured.
Related reading: The world's first HIV-infected person has passed away.
Here is his story "London patient"-the world's second HIV-infected person "London patient" called himself Adam Castillejo (Adam Castillejo).
An immigrant from Venezuela works as an assistant chef in London.
Because he had both leukemia and Hodgkin's lymphoma, the doctor gave him a bone marrow transplant.
He underwent a stem cell transplant in 2016.
Like the "Berlin patient", the bone marrow transplant donor he received also carried a mutation in the CCR5 gene.
Adam stopped taking antiviral drugs in September 2017, and no active HIV virus has been detected in his body for 18 months.
However, bone marrow transplantation is extremely risky and is only used for cancer patients who are dying because of the possibility of serious infections and complications.
The "Berlin patient" received the second bone marrow transplantation because of the tumor recurrence.
After the operation, he suffered serious neurological complications and almost became a vegetable.
In addition, the same method does not have the same effect on every patient.
Moreover, the entire treatment process and postoperative care costs are huge, and there are very few donors carrying CCR5 gene mutations.
This method cannot be widely promoted as a universal method for curing HIV-infected patients.
Related reading: Faced with death, the world's second cured HIV-infected person wants to tell you.
.
.
These AIDS patients can heal themselves (1) The elite controllers population-EC1 and EC2 for the world For 99.
5% or more of the 35 million HIV-infected people, drugs are the only way to suppress the virus, but for a small number of people, they are born to heal without medicine.
On August 26, 2020, a report published in the journal Nature pointed out that after analyzing more than 1.
5 billion cells extracted from a patient named EC2, it was found that none of these cells had normal Functional HIV copies.
Although no one can be sure whether the complete virus is hidden in a cell in his body, this finding suggests that some patients' immune systems may be able to clear harmful and stubborn viruses on their own.
An analysis of another patient named EC1 showed that only one in more than 1 billion blood cells carries a functional copy of HIV.
These two patients are part of a rare group called elite controllers, which means they can maintain very low or undetectable HIV levels without antiretroviral drugs, and there is no correlation Symptoms or obvious signs of damage by a virus.
"(Their control of HIV) is not just months or years, but extremely long-term.
" said Dr.
Satya Dandekar, an HIV researcher at the University of California Davis School of Medicine. (2) Why can they heal without medicine? Hypothesis 1: Genetic mutation researchers want to know how elite controllers suppress the virus for a long time, but it has been difficult to figure out because no one has recorded the first battle scene between HIV and the immune system of elite controllers.
"We missed the initial attack by the immune system against the virus.
Because when we knew that a person was an elite controller, the battle was already won.
" Dr.
Dandekar explained.
Dr.
Joseph Wong, a virologist at the University of California, San Francisco, said: “About a quarter of elite controllers have genetic mutations in key immune system genes, which may help them control the virus.
But this also explains why there are only a few.
This happens to elite controllers, and it’s difficult to transfer this situation to other people.
” Image source: 123RF Hypothesis 2: Infected with the defective HIV virus Dr.
Dandekar proposed that elite controllers may be infected with “moderate” "The version of HIV.
Therefore, the researchers tested the HIV virus embedded in the genomic DNA of 64 elite controllers and 41 HIV-infected individuals taking antiretroviral drugs.
The median time for these elite controllers to successfully control HIV levels without medications reached 9 years, while the patients named EC2 maintained undetectable levels of the virus for 24 years without medications.
HIV is a retrovirus, which means that its genetic information is stored in RNA.
Reverse transcriptase copies these RNA instructions into DNA, which can be inserted into the host's DNA.
However, reverse transcriptase is prone to errors and often leads to defective or incomplete virus replication.
"Therefore, we previously thought that elite controllers may carry defective versions that do not function properly and cannot produce infectious viruses," said Professor Xu Yu of Harvard Medical School.
The virus in most elite controllers is more complete than expected. "▲The life cycle of the HIV virus (picture source: NIH official website) Hypothesis 3: The place where the virus inserts into the patient’s DNA is different.
In most HIV-infected patients, the viral DNA is inserted near or near the gene encoding the protein in the human cell genome.
in.
researchers had thought possible in elite controllers, this virus trapped in called heterochromatin (heterochromatin) in a special area.
genes encoding proteins in these regions is less, and chromatin structure is not conducive to gene Activation and expression of
HIV.
Inserting HIV DNA sequences into heterochromatin is like putting HIV in a box and then locking it.
These HIV viral DNA may activate briefly and produce infectious viruses, but in most cases it does not Does not show activity.
Professor Xu Yu and colleagues studied whether elite controllers have a tendency to turn viral DNA to heterochromatin.
However, in the laboratory dish, the guide protein in elite controller cells still guides HIV insertion and approach The location of the gene is the same as in the cells of ordinary patients.
Therefore, it may not be that the elite controller was lucky enough to trap HIV in the heterochromatin at the beginning of the infection, but the immune system of the elite controller was eliminated to produce function The cells of the sex virus leave only the damaged copy of the virus and the complete version locked in the heterochromatin.
How the immune system of the elite controller does this is still unknown.
Image source: 123RF My story is important only because it shows that HIV infection can be cured.
If something can happen in medicine, it will continue to happen.
"——Timsey Ray Brown "I am not a child of choice, I just appeared in the right place at the right time, but I want to be a messenger of hope! "——Adam Castillejo Although there is no complete cure for AIDS, the widely used combination antiretroviral therapy (also called cocktail therapy) can effectively inhibit HIV replication and allow AIDS patients to Live like ordinary people for a long time.
Research on the immune system of elite controllers may bring hope to other HIV-infected patients.
Because once the mechanism behind it is figured out, scientists may find out what is wrong with other patients, adjust treatment plans and develop new therapies, and artificially make HIV-infected people use their own immune system to eliminate the virus.
We expect that with the rapid development of medical technology, people with AIDS can be cured and recovered and live a healthy life.
Source of title picture: 123RF Reference materials: [1] In a first, a person's immune system fought HIV — and won.
Retrieved August 26, 2021, from elite-controllers[2] Timothy Ray Brown, who inspired millions living with HIV, dies of leukemia.
Retrieved August 17, 2017, from timothy-ray-brown-obit.
html[3] Second HIV Patient in Remission after Stem Cell Transplant.
Retrieved March 15, 2019, from https://moffitt.
org/endeavor/archive/second-hiv-patient-in-remission -after-stem-cell-transplant/[4] Lopalco (2010) CCR5: From Natural Resistance to a New Anti-HIV Strategy.
Viruses, DOI: 10.
3390/v2020574 Note: This article aims to introduce medical and health research progress, not a treatment plan recommend.
If you need guidance on treatment plans, please go to a regular hospital for treatment.
Even after half a year or half a month, we are also husbands and wives.
When we die, we can be buried together upright, and we are also a home.
" "The Most" starring Aaron Kwok and Zhang Ziyi "Love" once made a lot of tears, because all the villages selling blood are AIDS patients, and all the villagers can do is bury each other and wait for death.
In the eyes of many people, "AIDS" and "terminally ill" are equated, but there is a small group of lucky people who successfully healed themselves or were cured.
Image source: 123RF "Berlin patient"-the world's first AIDS cured In 1995, American Timothy Ray Brown was diagnosed with HIV infection in Berlin, Germany, and was therefore called "Berlin patient" ".
To make matters worse, in 2007, he suffered from a blood cancer called acute myeloid leukemia (acute myeloid leukemia), so Timsey received a bone marrow transplant from a person with natural resistance to HIV.
The person who donated the bone marrow to Timsey happened to have a rare genetic mutation in a gene called CCR5.
There is a class of leukocyte chemotactic factors (chemokines) and corresponding cell receptors in the human body, which are involved in the immune regulation of leukocytes and lymphocytes.
The Chinese name of CCR5 is chemokine receptor 5, which is a protein receptor on the surface of white blood cells.
The CCR5 gene encodes this protein.
HIV specifically attacks CD4-positive lymphocytes in the human body, proliferates in the lymphocytes, destroys the lymphocytes, and causes cell lysis, thereby continuing to infect and destroy other lymphocytes.
Therefore, AIDS is also called Acquired Immunodeficiency Syndrome.As early as 1996, researchers discovered that in addition to CD4, CCR5 is one of the two co-receptors for HIV to enter cells.
Certain HIV strains need to bind to CCR5 on the cell surface to enter lymphocytes.
The CCR5 gene mutation is equivalent to locking the door, making people with this gene mutation resistant to HIV infection.
▲HIV invading lymphocytes need to bind to the CD4 and CCR5 receptors on the cell surface (Image source: US National Institutes of Health-National Institute of Allergy and Infectious Diseases, Public domain, via Wikimedia Commons) After receiving a bone marrow transplant, Timsey's body The newly generated lymphocytes all carry mutations in the CCR5 gene.
Therefore, HIV cannot enter its lymphocytes and cannot survive in the human body.
Three months after the operation, Timsey could no longer detect HIV in his blood.
He thus became the first AIDS patient in the world to be cured.
Related reading: The world's first HIV-infected person has passed away.
Here is his story "London patient"-the world's second HIV-infected person "London patient" called himself Adam Castillejo (Adam Castillejo).
An immigrant from Venezuela works as an assistant chef in London.
Because he had both leukemia and Hodgkin's lymphoma, the doctor gave him a bone marrow transplant.
He underwent a stem cell transplant in 2016.
Like the "Berlin patient", the bone marrow transplant donor he received also carried a mutation in the CCR5 gene.
Adam stopped taking antiviral drugs in September 2017, and no active HIV virus has been detected in his body for 18 months.
However, bone marrow transplantation is extremely risky and is only used for cancer patients who are dying because of the possibility of serious infections and complications.
The "Berlin patient" received the second bone marrow transplantation because of the tumor recurrence.
After the operation, he suffered serious neurological complications and almost became a vegetable.
In addition, the same method does not have the same effect on every patient.
Moreover, the entire treatment process and postoperative care costs are huge, and there are very few donors carrying CCR5 gene mutations.
This method cannot be widely promoted as a universal method for curing HIV-infected patients.
Related reading: Faced with death, the world's second cured HIV-infected person wants to tell you.
.
.
These AIDS patients can heal themselves (1) The elite controllers population-EC1 and EC2 for the world For 99.
5% or more of the 35 million HIV-infected people, drugs are the only way to suppress the virus, but for a small number of people, they are born to heal without medicine.
On August 26, 2020, a report published in the journal Nature pointed out that after analyzing more than 1.
5 billion cells extracted from a patient named EC2, it was found that none of these cells had normal Functional HIV copies.
Although no one can be sure whether the complete virus is hidden in a cell in his body, this finding suggests that some patients' immune systems may be able to clear harmful and stubborn viruses on their own.
An analysis of another patient named EC1 showed that only one in more than 1 billion blood cells carries a functional copy of HIV.
These two patients are part of a rare group called elite controllers, which means they can maintain very low or undetectable HIV levels without antiretroviral drugs, and there is no correlation Symptoms or obvious signs of damage by a virus.
"(Their control of HIV) is not just months or years, but extremely long-term.
" said Dr.
Satya Dandekar, an HIV researcher at the University of California Davis School of Medicine. (2) Why can they heal without medicine? Hypothesis 1: Genetic mutation researchers want to know how elite controllers suppress the virus for a long time, but it has been difficult to figure out because no one has recorded the first battle scene between HIV and the immune system of elite controllers.
"We missed the initial attack by the immune system against the virus.
Because when we knew that a person was an elite controller, the battle was already won.
" Dr.
Dandekar explained.
Dr.
Joseph Wong, a virologist at the University of California, San Francisco, said: “About a quarter of elite controllers have genetic mutations in key immune system genes, which may help them control the virus.
But this also explains why there are only a few.
This happens to elite controllers, and it’s difficult to transfer this situation to other people.
” Image source: 123RF Hypothesis 2: Infected with the defective HIV virus Dr.
Dandekar proposed that elite controllers may be infected with “moderate” "The version of HIV.
Therefore, the researchers tested the HIV virus embedded in the genomic DNA of 64 elite controllers and 41 HIV-infected individuals taking antiretroviral drugs.
The median time for these elite controllers to successfully control HIV levels without medications reached 9 years, while the patients named EC2 maintained undetectable levels of the virus for 24 years without medications.
HIV is a retrovirus, which means that its genetic information is stored in RNA.
Reverse transcriptase copies these RNA instructions into DNA, which can be inserted into the host's DNA.
However, reverse transcriptase is prone to errors and often leads to defective or incomplete virus replication.
"Therefore, we previously thought that elite controllers may carry defective versions that do not function properly and cannot produce infectious viruses," said Professor Xu Yu of Harvard Medical School.
The virus in most elite controllers is more complete than expected. "▲The life cycle of the HIV virus (picture source: NIH official website) Hypothesis 3: The place where the virus inserts into the patient’s DNA is different.
In most HIV-infected patients, the viral DNA is inserted near or near the gene encoding the protein in the human cell genome.
in.
researchers had thought possible in elite controllers, this virus trapped in called heterochromatin (heterochromatin) in a special area.
genes encoding proteins in these regions is less, and chromatin structure is not conducive to gene Activation and expression of
HIV.
Inserting HIV DNA sequences into heterochromatin is like putting HIV in a box and then locking it.
These HIV viral DNA may activate briefly and produce infectious viruses, but in most cases it does not Does not show activity.
Professor Xu Yu and colleagues studied whether elite controllers have a tendency to turn viral DNA to heterochromatin.
However, in the laboratory dish, the guide protein in elite controller cells still guides HIV insertion and approach The location of the gene is the same as in the cells of ordinary patients.
Therefore, it may not be that the elite controller was lucky enough to trap HIV in the heterochromatin at the beginning of the infection, but the immune system of the elite controller was eliminated to produce function The cells of the sex virus leave only the damaged copy of the virus and the complete version locked in the heterochromatin.
How the immune system of the elite controller does this is still unknown.
Image source: 123RF My story is important only because it shows that HIV infection can be cured.
If something can happen in medicine, it will continue to happen.
"——Timsey Ray Brown "I am not a child of choice, I just appeared in the right place at the right time, but I want to be a messenger of hope! "——Adam Castillejo Although there is no complete cure for AIDS, the widely used combination antiretroviral therapy (also called cocktail therapy) can effectively inhibit HIV replication and allow AIDS patients to Live like ordinary people for a long time.
Research on the immune system of elite controllers may bring hope to other HIV-infected patients.
Because once the mechanism behind it is figured out, scientists may find out what is wrong with other patients, adjust treatment plans and develop new therapies, and artificially make HIV-infected people use their own immune system to eliminate the virus.
We expect that with the rapid development of medical technology, people with AIDS can be cured and recovered and live a healthy life.
Source of title picture: 123RF Reference materials: [1] In a first, a person's immune system fought HIV — and won.
Retrieved August 26, 2021, from elite-controllers[2] Timothy Ray Brown, who inspired millions living with HIV, dies of leukemia.
Retrieved August 17, 2017, from timothy-ray-brown-obit.
html[3] Second HIV Patient in Remission after Stem Cell Transplant.
Retrieved March 15, 2019, from https://moffitt.
org/endeavor/archive/second-hiv-patient-in-remission -after-stem-cell-transplant/[4] Lopalco (2010) CCR5: From Natural Resistance to a New Anti-HIV Strategy.
Viruses, DOI: 10.
3390/v2020574 Note: This article aims to introduce medical and health research progress, not a treatment plan recommend.
If you need guidance on treatment plans, please go to a regular hospital for treatment.
