Pages

Harnessing innate immunity to cure HIV

Using a single drug derivative of vitamin A, researchers are now beginning to harness our innate immune system in order to force it to recognise, find and kill any cells infected by the human immunodeficiency virus (HIV), giving hope of a cure in the future. 

HIV particles (yellow) on the surface of a T cell, NIAID/NIH

Why we need a cure


Two of the major goals of HIV research are to develop a vaccine to prevent new infections, and develop a way to cure all the millions of people currently infected. Yet both goals have not been reached. According to the World Health Organisation (WHO), 36.7 million people are infected currently with HIV-1 (the most common type of the virus in man) and less than half of those infected are being treated with antiviral drugs. Unfortunately, the number of new people infected each year is dropping as dramatically as we would like, suggesting that we are not yet winning the war against this pandemic.

The fight against HIV has myriad weapons at its disposal, such as: global education strategies, cheap and accurate diagnostics, and antiviral drugs used to suppress virus replication, stop disease and onward transmission. But one thing that has proven to be very difficult is how can we cure all those people infected who are unable to eliminate the virus? The difficulty here is that HIV is expert in hiding from us. 

HIV - hiding in plain sight


Curing somebody from an HIV infection is challenging because of the fundamental biology of the virus (see this for an excellent review of this) HIV is a retrovirus, which means that it replicates by inserting a DNA copy of its entire genome (which is composed of RNA) into the genome of the cell that has just infected. From this DNA copy new RNA genomes are made. Once that copy is there then it cannot be removed.  One of the only ways that the DNA copy may be removed from our body naturally would be through the death of that infected cell but that might not be so simple. 

HIV can infect a kind of immune cell (specifically a T cell) that has the 'CD4' glycoprotein on its surface (CD4+ve 'helper' T cells). These cells from a part of our natural immune response where they interact with other immune cells and can promote an effective response. T cells are a part of the adaptive 'memory' immune system and as a consequence can live for a very long time. As HIV infects these cells, the inserted DNA copy also survives for years, still capable of producing new viruses. The long-lived 'resting' cells however, don't produce a lot of HIV, yet during some conditions these cells can become 'activated', causing them to divide, inducing the production of new HIV genomes, viruses and sustaining the infection.

Shock and kill


HIV antivirals stop these genomes producing viruses and infecting new cells but cannot touch the DNA copy residing in long-lived cells. A complete cure would have to eliminate any traces of HIV DNA from our cells. One strategy would be to activate HIV genome production at once in combination with a way to kill or block new infections, which is known as 'shock and kill'.

Shock and kill has a long history with many attempts focusing on using antivirals (or this), neutralizing antibodies or by promoting our own immune cells to kill the newly activated cells. This approach is challenging because of the need to balance viral activation without producing lots of activated and readily-infectable T cells and effective combination with an additional therapeutic, such as antivirals or antibodies that only block onward infection. However, a recent paper suggests that we could achieve HIV activation, kill those activated cells  and block onward infection using a  single drug by exploiting our own bodies' antiviral response. 

Innate immunity to the rescue


Li et al., reporting in Nature Medicine, show that by administration of a drug Acitretin - a derivative of retinoic acid, which is itself a metabolite of vitamin A - to human cells in the lab infected with HIV, they can kill cells that are infected with HIV.

The secret to how this is achieved is via the simultaneous induction of HIV RNA production and a human gene called DDX58, otherwise known as 'retinoic acid-inducible protein-I' (RIG-I) (which is known to be induced by retinoic acid and its derivatives). 

RIG-I is a very important antiviral protein that can detect viral RNA within the cytoplasm of a cell and kick-start an antiviral response, which can be characterised by cell death (apoptosis) and secretion of antiviral signalling proteins called interferons. In the case of Li et al., their anti-HIV affect following Acitretin treatment was dependent on RIG-I and associated with apoptosis and interferon production; apoptosis would destroy infected cells and the interferon may protect nearby cells (and help induce apoptosis) that are not infected yet, thus preventing the spread of infection. 

Is this a cure?


The simple answer is no. Or at least, not yet. While this study is a neat idea with potential, the work was carried out only in cells in the lab, although it included primary cells from patients with HIV. There are concerns whether these cells isolated from the bloodstream are representative of the long-lived T cells infected with HIV found in the organs of patients. Additional studies in appropriate animal models could clarify this. Other questions would be whether systemic treatment with Acitretin would reach all the infected cells? And how would your body react if all cells reactivated their infection, inducing apoptosis and interferon production, simultaneously? Might there be unwanted side-effects related to reactivation? Or even from Acitretin itself?

In conclusion, while a cure is a long way off, it would be an incredible tool in the response to the HIV pandemic and it is great to such diverse options such as described in this study, especially ones seeking to exploit our own innate immune system. I believe that by studying the interactions between viruses and the innate immune system at the level of the cell we will come up with new ways to make better, safer antivirals and vaccines for all viruses. 

7 comments:

  1. This comment has been removed by a blog administrator.

    ReplyDelete
    Replies
    1. Good day everyone my name is jackson sandra from U.S.A, I have this great opportunity to share this testimony about how I get cure for my HIV,Two years ago I was HIV positive so I was suffering from it I was doing one thing or the order to get a cure there was know way for it so I was on my research on the internet I saw a testimony of a young man, about how DR.AKHIGBE help him get a cured for HIV with his herbal medicine I was surprise and I do not believe I said okay let me try him I contact him that night on his email and he gave me instructions and I follow it he told me what to do and I did it, after a week he sent to me the medicine true DHL he told me how to use it and I did exactly how he instructed me to use it, after two weeks he told me that I should go for test, indeed I did it, and behold I was HIV "negative" am so grateful Doctor, now am happy with my Husband and two kids I want to use this opportunity to say this, please if you have this kind of disease called HIV, I want you to contact him on is email;DR.AKHIGBESPELLHOME@GMAIL.COM OR +2348106618681 and my email: jacksonsandra022@gmail.com and he can also help you get a cure for HPV, HERPES, CANCER,disease and he can cure you from any kind of diseases with his herbal medicine. all you have to do is to believe him. thank you my Dr may god bless you......
      HE FIX THE FOLLOWING PROBLEMS TO ALL ACROSS THE GLOBE ON:
      1. Getting your lover or husband back
      2. Spiritual bulletproof
      3. Prosperity spell
      4. Protection spell
      5. Get a job spell
      6. Becoming a manager spell
      7. Get a huge loan without paying any fee spell
      8. Child spell
      9. Love spell
      10, vanishing spell
      11. Success or pass spell
      12. Marriage spell
      13. Avenging spell
      14. Popularity spell
      15. Killing spell....

      Delete


  2. [b]DR Uroko is the only Dr who could ever get my HIV-AIDS cured with his healing spell, i have tried almost everything but i could’nt find any solution on my disease, despite all these happening to me, i always spend alot to buy a HIV drugs from hospital and taking some several medications but no relieve, until one day i was just browsing on the internet when i come accross a great post of !Michelle! who truly said that she was been diagnose with HIV and was healed that very week through the help of these great powerful healing spell doctor, sometime i really wonder why people called him Papa Uroko, i never knew it was alll because of the great and perfect work that he has been doing that is causing all this. so i quickly contacted him, and he ask me some few questions and he said a thing i will never forget that anyone who contacted him is ! always getting his or her healing in just 6 hours after doing all he ask me, so i was amazed all the time i heard that from him, so i did all things only to see that at the very day which he said i will be healed, all the strenght that has left me before rush back and i becomes very strong and healthy, this disease almost kills my life all because of me, so i went to hospital to give the final test to the disease and the doctor said i am HIV negative, i am very amazed and happy about the healing Dr Uroko gave to me from the ancient part of africa, you can email him now for your own healing too at:atitilovespell@gmail.com thank you sir for healing me from HIV, i am Doris Carter.

    ReplyDelete
  3. I'm maria cooker , I contracted HIV in 2009, I was told by my doctor that there's no possible cure for HIV. I started taking my ARV's, My CD4 was 77 and viral load was 112,450. I saw a website of Dr. amadu, also I saw a lot of testimonials about him on how he uses herbal medicine to cure HIV. I contacted him and told him my problems, He sent me the herbal medicine and I took it for 7 days after then I went for check-up and I was cured. The medicine has NO SIDE EFFECT, there's no special diet when taking the medicine. He also cure DIABETES, EX BACK, ALS, HEPATITIS B, CANCER, HERPES and lots more. You can reach him on dramaduherbalhome@gmail.com. or dramaduherbalhome@outlook.com. or call/Whatsapp +2349052645237_.

    ReplyDelete


  4. My name is Linda Anderson from Canada. I am here to give testimony on how I got heal of hepatitis virus,i have been suffering from this disease for the past 3 years ago.have been to different hospital and different spell caster, I felt like killing myself, my life became very bitter and sorrowful. hepatitis virus is a deadly disease i stayed away from my husband because i don't want to transfer it to my family until one very good day i was directed by my friend to Dr Omoa a great spell caster who cased a spell and i was healed of the disease.i didn't believe it because I've worked with so many of them and it didn't work. She begged me further so I decided to try this great spell caster called Great Dr Omoa. I still didn't believe, but inside me i wanted to give a try and as God will have it, i used the spell solution he gave me and the next day I went to the hospital to carryout a test,after the test i went home the next day i received a call from my doctor and he told me i was NEGATIVE.i didn't believe it because it was like a dream I'm very happy now with my family it worked for me and i believe it will work for you too just give him a try and follow up this is a clear truth from a testifier. Thank you Dr Omoa once again, if you want to reach him via email: (dradanikesolutionhome@outlook.com) WhatsApp him or call +2348141309378

    ReplyDelete
  5. Good day everyone my name is jackson sandra from U.S.A, I have this great opportunity to share this testimony about how I get cure for my HIV,Two years ago I was HIV positive so I was suffering from it I was doing one thing or the order to get a cure there was know way for it so I was on my research on the internet I saw a testimony of a young man, about how DR.AKHIGBE help him get a cured for HIV with his herbal medicine I was surprise and I do not believe I said okay let me try him I contact him that night on his email and he gave me instructions and I follow it he told me what to do and I did it, after a week he sent to me the medicine true DHL he told me how to use it and I did exactly how he instructed me to use it, after two weeks he told me that I should go for test, indeed I did it, and behold I was HIV "negative" am so grateful Doctor, now am happy with my Husband and two kids I want to use this opportunity to say this, please if you have this kind of disease called HIV, I want you to contact him on is email;DR.AKHIGBESPELLHOME@GMAIL.COM OR +2348106618681 and my email: jacksonsandra022@gmail.com and he can also help you get a cure for HPV, HERPES, CANCER,disease and he can cure you from any kind of diseases with his herbal medicine. all you have to do is to believe him. thank you my Dr may god bless you......
    HE FIX THE FOLLOWING PROBLEMS TO ALL ACROSS THE GLOBE ON:
    1. Getting your lover or husband back
    2. Spiritual bulletproof
    3. Prosperity spell
    4. Protection spell
    5. Get a job spell
    6. Becoming a manager spell
    7. Get a huge loan without paying any fee spell
    8. Child spell
    9. Love spell
    10, vanishing spell
    11. Success or pass spell
    12. Marriage spell
    13. Avenging spell
    14. Popularity spell
    15. Killing spell....

    ReplyDelete

Markup Key:
- <b>bold</b> = bold
- <i>italic</i> = italic
- <a href="http://www.fieldofscience.com/">FoS</a> = FoS