Low cholesterol in immune cells slows HIV progression


April 28, 2014
Health

Scientists at the University of Pittsburgh have identified why some HIV-infected people experience much slower disease progression, even without medication, and it has to do with cholesterol levels in specific immune cells. They report their findings in mBio®, the online open-access journal of the American Society for Microbiology.

“A fascinating aspect of the AIDS epidemic is that a small percentage of HIV-1-infected persons, termed nonprogressors or controllers, maintain a relatively normal number of CD4 T cells (Th cells) and low viral load for many years without receiving antiviral therapy,” says lead author Giovanna Rappocciolo. “Knowing how these individuals naturally control their HIV-1 infection and prevent the virus from progressively destroying their Th cells could be critically important to developing effective therapeutic and prevention strategies for HIV-1/AIDS.”

When HIV enters the body, it is typically picked up by immune system cells, called antigen-presenting cells (APCs), including dendritic cells and B lymphocytes. Those cells then transport the virus to lymph nodes where the APCs pass it to other immune system cells, including Th cells, via a process known as trans infection. HIV then uses Th cells as its main site of replication. It is through replication in the Th cells that levels of HIV increase and overwhelm the immune system.

Even without antiretroviral drugs, approximately one in 20 people infected with HIV do not have the persistent increase in levels of HIV after initial infection and can sometimes go many years, even more than a decade, without the virus seriously compromising the immune system or leading to AIDS.

In the study Rappocciolo and her colleagues compared the ability of APCs from nonprogessors, progressors and uninfected control subjects to trans infect T cells. They found that while the cells from progressors and control subjects were highly effective at mediating trans infection, those from nonprogressors lacked the ability.

The researchers took a closer look and discovered that the APCs from nonprogressors had low levels of cholesterol, even though the patients had regular levels of cholesterol in their blood. Moreover, they found that trans infection could be restored by reconstituting cholesterol levels in the APCs of nonprogressors and could also be inhibited by reducing the cholesterol levels in the APCs of progressors.

Additionally, analysis of APCs from two nonprogressors obtained one to four years before primary HIV infection shows similar results, suggesting this is a genetically acquired trait.

“This defect in cholesterol metabolism is not a direct consequence of virus infection, but rather is likely present as an inherited trait in a low percentage of individuals. Understanding how this works could be an important clue in developing new approaches to prevent progression of HIV infection,” says Rappocciolo.


23 Responses to Low cholesterol in immune cells slows HIV progression

  1. u14127212 May 2, 2014 at 2:08 pm #

    It is encouraging to know that patients that are infected with the HIV-virus can survive for a longer period of time, even a decade without showing an increase in HIV levels or signs of attacking the immune system.

    This is possible because the person simply has low level of cholesterol and shows a slower rate of progression. At this stage only a small percentage of HIV-1 infected patients are nonprogressors, only about 1 in ever 20 HIV patients.

    Lets hope with these breakthroughs in research of HIV and Aids, somebody can soon find a complete cure for this growing virus which affects many people world wide but especially in Africa.

  2. u14019079 May 2, 2014 at 8:10 am #

    I feel this study is a breakthrough in how HIV and AIDS is studied, even though it is a deformity that causes the virus not to respond to its surroundings it is a vital part to survival to that human host that has the deformity. I feel mutation of genes has become a survival mechanism to human through the years just as sickle-cell anemia, a deformity in red blood cells that help the individual from contracting the disease Malaria, helps human hosts survive in a bisarre way.
    I feel that this is a part of natural selection and if scientists can understand the mutations in our bodies and why a mutated gene helps prevent a disease can play a vital role not only in prevention and curing of the disease but in the techniques used in studying the disease.

  3. Brittany Hopkinson14070988 May 2, 2014 at 3:31 am #

    This study could have the potential to be a breakthrough in the research of HIV and AIDS and in researching a stable treatment and cure for it. The research in the past for an effective treatment and cure for HIV and AIDS has been remarkably difficult as the virus mutates and changes so rapidly that research behind it can’t keep up with such mutations. The fact that the disease progresses so slowly in people with higher cholesterol levels or in individuals with genetically acquired familial hypercholesterolemia may have some key or link to how this disease could potentially be treated more successfully or ultimately cured and therefore could initiate more research into this particular topic.

  4. Brittany Hopkinson 14070988 May 2, 2014 at 3:24 am #

    This is and extremely interesting study which could lead to a major breakthrough in the research of HIV and AIDS and in researching a stable treatment or cure for it. The research in the past for an effective treatment and cure for HIV and AIDS has been remarkably difficult as the virus mutates and changes so rapidly that research behind it can’t keep up with such mutations. The fact that the disease progresses so slowly in people with higher cholesterol levels or in individuals with genetically acquired familial hypercholesterolemia may have some key or link to how this disease could potentially be treated more successfully or ultimately cured and therefore could initiate more research into this particular topic.

  5. u14004951 May 1, 2014 at 11:39 pm #

    I would like to clarify a misunderstanding regarding this new research.

    One does need to realize, after reading this article that it does not imply that a low cholesterol intake slows down the HIV progression. The article implies that research is being done on a genetic trait where people, who have low cholesterol levels in their antigen preventing cells (APC’s), yet normal blood cholesterol levels, have a slower HIV progression. Thus, a big misunderstanding is developed: Researchers are trying to find ways in reducing cholesterol levels in APC’s of patients, NOT necessarily in the blood of patient.

    Interestingly enough, research is on-going about whether cholesterol in foods is really such a “killer” and “heart daemon”. After admitting and realizing that the traditional food pyramid is not in actual fact the most healthiest, Professor Tim Noakes explains that for a healthy lifestyle we should be eating high fats, high proteins, low carbohydrates and no sugar. We should be living a primitive life-style in what we eat and instead of merely eating fat-free products; we should be eating as much natural fats as what we can.

    Although this diet is seems to be irrelevant to the HIV pandemic, I do believe that what HIV infected people eat do contribute greatly to their health. Perhaps this new understanding of cholesterol and diet could help develop the understanding of how one achieves low cholesterol levels in APC’s, yet normal healthy levels in one’s blood.

  6. 14006872 May 1, 2014 at 12:55 pm #

    It was suggested earlier that APCs with low cholesterol in nonprogressors is a genetically acquired trait. Synthetic biology now allows for genes to be produced in a laboratory. Perhaps a gene with this trait could be mass produced synthetically. Genes can also now be added to the human genome. For example, certain alleles of Apo-lipoprotein E are added for protection against Alzheimer’s disease. Can the same concept be applied to APCs? Adding this gene to the human genome would allow for a larger number of nonprogressors. Therefore, more people with the HIV would have a higher life expectancy. This would also greatly reduce the cost factor for ARVs as less of the drug would be needed. While the discovery of low cholesterol APCs in nonprogressors will most probably not lead to a cure for HIV, it could drastically improve the lives of HIV positive patients.

  7. 14087902 May 1, 2014 at 3:50 am #

    HIV/AIDS has been a detrimental syndrome affecting many countries especially South Africa. The discovery that low cholesterol inhibits the rate at which the virus destroys the body’s immune system is one step forward into finding a cure for this disease. This discovery could even be considered as a breakthrough in medical science as this disease has been the cause of thousands of deaths.
    This discovery may even lead to other therapeutics that would inhibit or even prevent the disease. This would be called a “prevention mechanism” that could even elongate the time period at which you can destroy the virus before it actually develops into AIDS. This would help people in areas that have limited resources as they may have a longer period rather than 72 hours to get ARVs.

  8. John Snow April 30, 2014 at 11:52 pm #

    :):):)

  9. Givarn Seetal(14050252) April 30, 2014 at 4:45 pm #

    This article presents some truly important information with regard to the development of a cure and management of HIV. A better understanding of the way the virus operates and progresses allows people who are victims of the virus to control the infection in a way which may be less painful than taking ARVs. HIV is a serious problem locally and globally, and education about management and contraction of the disease is therefore necessary.

    In response to Liliza’s question in treating HIV with nanotechnology, a treatment for cancer using nanotechnology has been developed using Zinc oxide nanoparticles. This was possible since cancer cells are cells, and not viruses. This means that they can be killed and targeted relatively easily in comparison to a virus- which is not a living cell and is many times smaller than a cell.

    Keleabetswe asked if lowering cholesterol reduces a baby’s chances of contraction- and I would say that the baby’s chance of infection remains the same irrespective of the mother’s cholesterol levels. I think this may be the case simply because low cholesterol reduces the development of the disease in an infected individual- so it doesn’t change the fact that the person has the virus and therefore does not change the chance of transmission through birth, intercourse etc. It is possible however for a HIV positive mother to give birth to a HIV negative child, if the mother follows a specific treatment.

  10. Sakhau Refiloe (14160812) April 30, 2014 at 3:45 pm #

    For far too long the topic of HIV/AIDS has been associated with an atmosphere of despair due to the fact that here hasn’t been any cure for this disease and the people who are infected have to live on medication for the rest of their lives, which does not make living with the disease any easier. It is such discoveries that can give people a renewed sense of hope that a cure for HIV is not so far-fetched after all.

    Considering how a person with a low cholesterol level tends to show a slower rate of progression with regard to the multiplication of the HIV virus in the individual’s immune system and the advancement of HIV to AIDS, I would like to know if cholesterol could be used to manipulate the progression rate HIV virus in the immune system to an extent where it is possible for the virus to reach a state of dormancy ? Should this be possible, would it also mean that if the HIV virus were dormant, it decreases the chances of passing it on from one individual to the next ?

    Looking at this from a different angle, the use of stem cells has had an incredible impact on the advancement of science and medicine, do you think that stem cells hold the secret to the cure for HIV/AIDS ? I heard a story once about an HIV-positive man who also had Leukemia. Doctors could obviously do nothing about his HIV but through the use of stem cell his leukemia was curable. After undergoing treatment in an attempt to cure the leukemia it was found that the HIV was no longer present in the man’s bloodstream … What is your take on this ?

  11. 14120692 April 30, 2014 at 11:49 am #

    Over the past few years, HIV has become highly prevalent amoungst the global population. There are many reasons for this rapid increase such as; lack of education and insufficient availability to necessary medical resources, to name the central points, in my opinion. These two aspects interlink as when patients are given the correct medication, many do not complete the course and thus the virus develops strains that become resistant towards the medication and thus the spread continues.

    Scientists have discovered new research towards the progression of HIV, as mentioned above in the article. They suggest that the progression is slower amoungst patients who have lower cholesterol in their immune cells. This research has shown that low cholesterol in the immune cells of patients can only be hereditary. However, with technology advancing at its current rate, through genetic engineering scientists could lower the cholesterol in the immune cells and slow the progression of HIV in our global population.

  12. 14105269 April 30, 2014 at 9:09 am #

    The immunity which 1% of Northern Europeans bear against the HI Virus is caused by the absence of a binding protein usually present in the human T-helper cell. T-cells with this mutation may introduced into an adult’s body via bone marrow transplant, as was the case with The Berlin Man, who was cured entirely of HIV. If a combination of genetic engineering, stem cell harvesting and cholesterol control is used, may a cure finally be developed for HIV?

  13. 14121124 April 30, 2014 at 6:54 am #

    It is suspected that 33.4 million people are currently living with HIV, while the struggle to find a cure or vaccine continues. Due to HIV’s high variability, rapid mutation, DNA- binding property and the high cost of research; a cure or vaccine is very difficult to create.

    Discovering why the disease progression in some is much slower than in others could allow us to create a vaccine, which would possibly lower the cholesterol levels in the antigen-presenting cells thus preventing or delaying the process of trans infection, where the virus is passed to the CD4 cells in the immune system, which ultimately allows the replication of the virus.

    This unique approach could be effective as it doesn’t target the actual virus. The HIV virus is constantly evolving and has many strains, thus making the virus very difficult to target as the virus just evolves, making the ‘cure’ void.

    The vast majority of people infected with HIV do not have access to ARVs, and the question is if this vaccine is successfully created will the low and middle income populations have access to it? Because they constitute 97% of the living HIV population and therefore they should be the main target market.

  14. 14004870 April 29, 2014 at 11:00 pm #

    Who would have thought that low cholesterol would slow the progression of the HI virus in our bodies.It it evident that science,technology and health are evolving as time flies.For an individual who believes that there is a cure for HIV/AIDS somewhere,I am pleased to know that there are other alternatives present to treat the disease and prevent the rapid spread.My greatest concern is that not a lot of people are informed about this latest discovery and secondly the minority of the people actually have a low level of cholesterol.If we were to evaluate a poverty stricken community, it would be hard for a lot of people to maintain a healthy diet and regulate a low level of cholesterol therefore,this new discovery would basically be applicable to people who can satisfy their basic needs and wants.

  15. Lizanne Bester (u14100313) April 29, 2014 at 2:14 pm #

    My comment is twofolded:

    First of all, I have worked at the Themba Lethu Clinic in the Helen Joseph hospital over the period July 2012. I have worked together with Dr. Motloung, consulting HIV-positive patients everyday! I have seen a variety of cases of very very ill patients. One of the reasons being not taking ARV’s on a regular basis or not taking them at all, because of the fact that the ARV’s making them feel sick-which many can not afford- being the majority of reasons. And this is when I realised the value of education!!!!

    Secondly, as mentioned above, the shocking statistic of only one out of twenty people that are infected with the HIV-virus, that can go for a very long period of time, sometimes even more than a decade, without showing an increase in the levels of HIV and thus meaning that there are no observable signs of the virus attacking the immune system or leading to AIDS. This is because of low levels of cholesterol in the immune system, making the HIV-infected person a nonprogressor.

    My point is that I personally think a campaign should be led to educate HIV-positive patients about the value of ARV’s and the consequences that will be faced when not taking them regularly, or not at all. The campaign should also guide the patients to healthier lifestyles, suggesting a low cholesterol diet for instance.

    This campaign will deliver multiple results: knowledge of a healthier lifestyle will increase the statistic of the nonprogressors from one out of twenty to maybe ten or fifteen out of twenty!! Who knows!?? For the long term this means that a lot less patients will be dependent of ARV’s and that patients will use it for a way shorter period of time, when results become visible. This will then result in a decrease of ARV supply by the government, decreasing a lot of their financial stress!!! A continuous cycle of only positive results!!!

  16. Liliza Kinnear April 29, 2014 at 12:52 pm #

    I know with cancer, for instance, scientists use nanotechnology to deactivate the cancer in the cancer cell in a human’s body. Is it possible to do that with cells that has been infected with the HIV virus? Is it possible to deactivate the HIV virus from cells that has been infected with the HIV virus in a human’s body with nanotechnology?

  17. 13053648 April 29, 2014 at 9:01 am #

    HIV continuous to be a world wide pandemic with an increases gradually in number of people affected. Process in research has been slow despite it being one of the most funded medical research. This has brought people to question whether the most research is a money scheme, and even if a cure is developed hoe w much will it cost?

    Even so with the every increasing statistic on HIV patients it is important to find a way to preserve human life no matter the cost. That is why strives need to be made. Like with the case of the research conducted above, where it was shown that the disease is less progressive in people who have inherited a low level of cholesterol within the immune cells such patients had a lower rate of decline as the CD4 T cells. This gives a better understanding of how the virus affects different patients, and that this was a discovery that the virus is not only affected by lifestyle chooses by genetic plays its role. Is it possible hat such a discover and overs like it could led to the cure some day.

  18. Keleabetswe Tabane (14359805) April 29, 2014 at 7:54 am #

    There has been a high impact of the HIV epidemic on individuals, families and communities for many years. The discovery of how the HIV progress can be slowed down show that there are innovative researches that are being conducted to help fight this HIV epidemic. Such research discoveries give hope to those who are affected by this disease that the cure for this disease is close to being discovered. I would like to know, if an HIV positive pregnant women has low cholesterol in immune cells does this reduce the chances of her passing on the disease to her infant?.

  19. 14079667 April 29, 2014 at 5:14 am #

    So there is all this discussion about recent discoveries and breakthroughs in the science world and how these will help save lives and lead to cures. However, there is no concentration on the finance or time frame concerned.

    If we focus on all the past scientific discoveries and possible cures, how many times have these methods,unfortunately, failed. I believe that one day there will be a cure for cancer and HIV and many other diseases that ruthlessly consume lives every year, but unfortunately we live in a world of progressing separation and I have to ask myself, “if these cures were invented, how much would they cost and would the people affected, who are majority lower-class citizens, even be able to afford this amazing new life saver?”

    At the moment, government pays for antiviral drugs and perhaps if a cure is invented the government would be willing to pay for those affected, but once again, how long is this going to take?

    While we sit at home in our cozy, air-conditioned rooms is there nothing we can do to help speed up the process and ensure a financially sound and quick cure for a disease which has already, and will, take the lives of our loved ones?

  20. N. Mbense, 14121672 April 29, 2014 at 3:20 am #

    The struggle to find a cure for HIV is a great one. However, with studies such the above-mentioned booming, portrays that the scientific community perseveres to find one; ultimately helping the millions infected by it.

    One can have hope though. A study was conducted at the UCSF-based SCOPE over two years on a Berlin man who was HIV positive. A series of HIV persistence was applied to the study of this man. (He showed evidence of cure after a stem cell transplant). There was no HIV found in blood cells, spinal fluid, lymph node, or small intestine, and no infectious virus was recovered from blood. However, traces of the virus was detected in plasma. The analysts believed this to be false positives as it was in considerably low amounts. The Berlin man was thought to have been effectively cured because of the lack of rebounding virus after five years of no therapy, failure to isolate infectious virus and waning HIV-specific immune responses observed.

    So, not all hope is lost because with technology and science constantly growing, a cure for HIV is not far off.

  21. SB.Mtabela(14098408) April 29, 2014 at 2:46 am #

    HIV is a very detrimental disease one can acquire. This discovery of having to find that a person with low levels of cholesterol in the blood, has a low chance of having to have a slow progression of HIV cells accumulating in the body, is in fact true. This is due to that, a person with high levels of cholesterol in the body has an increased chance of having a week immune system. This is a problem one can have because this diminishes the white blood cells in the body which help destroy foreign substances that enter the body. This increases the progression of HIV cells accumulating in the body. Thus, this will cause AIDS in the end and also decreasing the chance of living longer.

    But on the other hand, the person with low levels of cholesterol in the blood has a high immune system and this activates the white blood cells which help fight against HIV cells without the help of ARVs .This in the end helps increase the life of that certain individual

  22. Joseline Iga Nkhoma (14044138) April 29, 2014 at 1:25 am #

    Every day we are getting closer and closer to finding a cure for HIV -1/AIDS. We may not have a cure yet but a way to slow down the progression of the HIV-1 into AIDS is already another amazing milestone.

    This research correlates with the research done by the University of Pennsylvania on Gene Therapy. Researchers discovered that about 1% of the Northern Europeans have a genetic mutation that prevents the AIDS virus from infecting the white blood cells (T-Cells). The plan is to make normal T-Cells HIV immune which could potentially lead to a cure. Researchers engineered a gene mutation by removing a receptor the HIV Virus needs to infect cells. The altered cells were placed back into HIV positive patients who then decreased the virus in some with one patient having no levels of HIV. If the immune system becomes immune to HIV there would be no need for ant-retrials.

    Now just imagine if the same genetic engineering is applied to stem cells. These cells would make lots of immune white blood cells which could be a long term cure.

  23. Jani van Wyk 13005856 April 28, 2014 at 10:05 pm #

    In 2012, there were 35.3 million [32.2 million–38.8 million] people living with HIV. Since the start of the epidemic around 75 million [63 million–89 million] have become infected with HIV. Looking at statistics like these we can see that HIV is a global problem and finding a cure for this disease could mean saving millions of people’s lives.
    The discovery that show HIV-infected people experience much slower disease progression, even without medication has to do with cholesterol levels in specific immune cells is groundbreaking. This is a vital prevention strategy that they have been looking for.
    APCs from non progressors had low levels of cholesterol, even though the patients had regular levels of cholesterol in their blood. The big question now is how are they going to help people with high levels of cholesterol in their blood? What are the strategies going to be?

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