World Community Grid Final Results

To date, we have completed 38 FAAH tasks, with 2 more in progress. You can view our progress by going to the following website: http://www.worldcommunitygrid.org/ms/viewMyMemberPage.do.

1) What is the estimate of h^2?
Technically, HIV is not genetically heritable since there is no 'HIV gene' that codes for the disease. Likewise, HIV is predominantly transmitted via non-heritable pathways: unprotected sexual relations, unscreened blood transfusions, needle-sharing, etc. However, there a certain instances when HIV is heritable from mother to child. The transmission of the virus from the mother to the child can occur in utero during pregnancy and intrapartum at childbirth via the placenta. In the absence of treatment, the transmission rate between the mother and child is around 25 percent (Coovadia). However, where combination antiretroviral drug treatment and Cesarian section are available, this risk can be reduced to as low as one percent (Coovadia). Breast feeding also presents a risk of infection for the baby.

Coovadia H (2004). "Antiretroviral agents—how best to protect infants from HIV and save their mothers from AIDS". N. Engl. J. Med. 351 (3): 289–292.

2) How much influence does selection have on this trait?
Selection starts to influence the transmission of HIV when the person develops AIDS and begins to get sick. While the person is infected with HIV but not showing symptoms of AIDS, selection does not influence it. Concerning the virus itself, selection plays a big part when it is being medically treated. Selection influences HIV as the virus rapidly mutates at random and creates new strains of the virus within the host. Through finding treatments for the virus, the strains which are resistant to the treatment are selected for and become prominent within the host. If the treatment changes or is terminated, a new strain may be selected for. For example, when AZT is being used to treat HIV, the viruses with the mutation to recognize and circumvent AZT will survive while those without the mutation will not.

3) What effect would inbreeding have on this trait?
Inbreeding does not effect the transmission or development of HIV.

FightAIDS@Home World Community Grid

To date, we have completed 33 FAAH tasks, with 2 more in progress. You can view our progress by going to the following website: www.worldcommunitygrid.org.

HIV Questions

1) Why is the elevated mutation rate in HIV a positive aspect for this phylogenetic study?
The elevated mutation rate in HIV creates multiple different strains. Because of these differences, certain infectious strains can be easily traced between patients. The ability to trace each strain by its mutations allows for this study to determine if the outbreak in Glenochil prison came from the same source.
2) What do env, pol and gag code for in HIV? Why do they differ in their mutation rates? Why, then, did this study choose to sequence gag and env?
Env codes for a protein, gp160. It is the protein that creates the markers on the outside of the HIV virus. Pol codes for four proteins, reverse transcriptase, protease, RNAse H, and integrase. Gag codes for the capsid protein, the matrix protein, nucleocapsid protein, and p6. They differ in mutation rates because the genes code for different proteins. Certain proteins, such as reverse transcriptase, cannot have significant mutations or they will not work; therefore, the gene pol cannot readily mutate and have the virus survive. This study choose to sequence gag and env because the mutation rates and high, which creates distinct similarities among related strains. (Dan Stowell http://www.mcld.co.uk/hiv/)
3) How can you tell, by lookin at the phylogenetic trees, that there is a single source of infection for the Glenochil cohort? Could you accurately describe the HIV genes in these prisoners as orthologous? Why or why not?
Each virus goes back to a common ancestor. The genes could technically be called orthologous because HIV started as SIV in monkeys, however, I would not call them orthologous because the mutations in the genes arose in one species, humans.
4) Why was it important to include unrelated HIV strains in this phylogentic analysis?
Showing the unrelated HIV strains allows for comparison of the strains that the study was focusing on. If there were no related strains, it would look as though the different strains in the patients all came from different sources.
5) Have there been other measures taken to reduce the spread of HIV in prisons since this paper was written (10 years ago)? At blood center like the one your interview described?
In countries other than the US, prisons have instituted condom distribution and needle exchange programs to combat behaviors such as unprotected sex and intervenous drug use. (Kelly, Christopher and Hiller, Matthew. "HIV, Public Health, and Corrections: Policies and Implications") Prisons in the US have started treating HIV + inmates with antiviral medications and also administrating counseling. (Center for AIDS Prevention Studies - University of California, San Fransisco)

6) On the next page you will find a figure from Science entitled "Application and Accuracy of Molecular Phylogenies" (Hillis et al. 1994: Vol. 264: 671-677). In the study referenced, the authors considered the allegations of 7 patients (A-G) that they had contracted HIV from their dentist. Were their allegations correct? Describe how the authors might have generated this tree.

It is a high possibility that these 7 patients were correct in saying they contracted HIV from their dentist. After extensive studies in which their viral gene samples were studied and compared/contrasted against the samples from the dentist and local population individuals, it was noted that a single evolutionary lineage exists between the dentist and the effected patients. Although there are potential confounding variables when considering the spread and evolution of this disease, the generated phylogenetic tree included all the patients without other identified risk factors and excluded all patients with other confirmed risk factors. It is consistent with the independent epidemiologic data and further studies have proven this phylogenetic tree to be an accurate representation of the spread of the disease between the dentist and patients.

Transmission of SIV to humans

Here are a couple of pictures that Dr. Nemechek provided us. They show how the apes are slaughtered at the Kinsasha meat market in Africa, which is how the SIV virus was transfered to humans. The conditions are not very sanitary and there is no regulation on testing of the animals before they are sold. Many people have misconceptions about how humans were infected with SIV, so this will, hopefully, help.

An Enlightening Interview

On Monday, February 16th, at 8:00 AM Amber and I met with Dr. Nemechek. He is a specialist in HIV/AIDS and had a great deal of valuable information to offer us. Here are his responses to the following questions:

1) How did you get into this field?
Dr. Nemechek said it all started when he was at UCLA in the late 1980's for his residency in internal medicine. He noticed that there were many young men who were dying and there was very little concern for them. These men were very low priority because they were either gay or drug users. There was overt bigotry throughout the hospital.
Originally, when Dr. Nemechek started his undergraduate studies, his goal was to be a high school teacher. This was because he has a strong belief of how to teach and he continued to carry that with him even as his goals changed. This came into play when the senior physician was teaching them during rounds. He was making comments that were immoral and horrible, all the while he had this huge influence on everyone around him. This influence was an abuse of his power and it struck Dr. Nemechek.

Because of all of his experiences during his residency he said, "HIV picked me." He couldn't raise his voice about all of the injustices because he would be thrown out of the program, but when he completed the residency program he was offered a teaching position in the hospital. In this position, Dr. Nemechek took all of the HIV patients. It was the first HIV clinic at UCLA and it was simply his residency clinic. Many people were speaking out about HIV patients and how they were not worthy of care until Magic Johnson announced that he was infected. After that, people stopped criticizing HIV patients out loud, but the emotions were still there. Whenever another doctor made a comment, Dr. Nemechek called him out about it because he believed that they were teachers and they were making an impression on the other doctors there.
Eventually, he was forced off of the teaching staff by the chief of surgery because he believed that Dr. Nemechek was trying to kill him by having him operate on HIV patients. He was never one to carry a banner before but in this instance Dr. Nemechek said, "It was one of those times to stand up and be counted." He said he would do it again, but the price would be higher.

2) Why does a doctor, especially one studying HIV and other retroviruses, need to know about evolution?

"Every doctor, in every field, needs to know about evolution." Dr. Nemechek explained how humans were designed to be prehistoric people. They were lean and survived on high protein. Their immune systems were built for when there was no food and for when they ate raw meat. Now we are trapped in a cultural context of what is healthy. For example, drinking eight serving of eight ounces of water is not needed to be healthy. The palaeolithic human did not need that to be healthy, so we don't either. Another example of how we were designed and how we don't live that way is diabetes. This is because of carbohydrates and obesity. The average American, now, eats one to two cups of carbohydrates a day. The prehistoric man ate one to two cups of carbohydrates a year. How we were designed explains how things function now. "We can go back and understand why something is the way it is now by looking at the past and they way it was then. If it hadn't worked, they [the organisms] wouldn't have survived."

3) Why is a search for the cure so important?

Dr. Nemechek said, "There really isn't a search for a 'cure.' That is not the goal in HIV medicine. Any time you use a treatment targeting DNA, the risks skyrocket." This is evident with the use of chemotherapy. When someone is treated with chemotherapy, the incidence of leukemia increases.
The goal of HIV medicine is to put the infection to a point where it is stable, or where the patient can live with the infection. All this takes is a small shift of something in HIV. Part of the problem of finding this is the cost and difficulties especially in other countries that have a higher rate of infection and lower living conditions. Another problem is that most deaths are caused by secondary infections that attack the immune system when the disease has progressed to AIDS. The heightened immune response at the start of the infection later leads to rapid decline when the later stages of AIDS are reached, the immune system is weakened, and no longer has the ability to fight off secondary infections a healthy individual could survive.
Dr. Nemechek said that we need to look to the populations of Sooty Mangabeys that live with SIV (Simian Immunodeficiency Virus). These apes have a high viral load but their immune system doesn't recognize it so the system doesn't kick in. If SIV is injected into Rhesus Macaques, who have never been exposed to the virus, it progresses much in the same way that HIV does in humans. Evolution explains why the Sooty Mangabeys can live with SIV and the Rhesus Macaques cannot. The Rhesus Macaques have not had the evolutionary pressures that the Sooty Mangabeys have to develop a resistance to the virus. Over time the immune systems of the Sooty Mangabeys have developed in a way that it no longer recognizes the virus as a threat, therefore not responding to infection or heightening immune system response. It is the same with FIV (Feline Immunodeficiency Virus). Felines in Africa live with the virus, but other cats infected with the virus without prior exposure progress to conditions that are the equivalent to AIDS.

So to treat humans, "We may need to target immune systems to ignore it instead of target the virus." It can be as simple as a vaccine. "The smallest shift in some part of the disease process is all that is needed to dramatically change the time of death." If we could lower the rate of transmission by 25% there would be a huge impact on the epidemiology of the virus.
Finding a cure is a high mark; lower marks are more attainable.

4) You just discussed how the immune systems in the primates of some regions have evolved to the point of no longer reacting to SIV. That said, do you think with the right amount of time, humans can evolve to the point where our immune systems will not react to HIV?
Theoretically yes. Humans have evolved against malaria with sickle cell.

5) What do you know about grid-computing? Do you believe it would be effective in contributing to a cure for AIDS?
Dr. Nemechek said that he doesn't know enough. He knows that it is a way to speed up results and it is a very unique tool. Drugs can be designed on blueprint. They can be genetically designed for a weak spot on the bacteria. It takes massive amounts of computer technology to figure the molecular structure and with this structure drugs can be designed to target the weak spots.

6) How long can HIV exist outside the body, if at all?
Just seconds to minutes until the source dries up.

7) Why is AIDS considered a pandemic?
Dr. Nemechek said that is it considered a pandemic because it is affecting the whole world. It is one of the most powerful influencers of the economy and politics in the world. For example, in Africa HIV wiped out all of the gains that took decades to achieve in just ten years. It increased the secondary illnesses.

8) Is there any evidence for how long HIV has been around?
SIV is suspected to have been around for thousands of years. This explains the evolutionary development of immune response resistance to the virus in the Sooty Mangabeys as enough time has passed for this resistance to develop. HIV is a much younger infection and is believed to have been around for a couple hundred of years.  There is documented evidence of specimens with HIV from the 1930's but it is expected that it has been around for much longer. There is evidence of HIV existing in Africa before the pandemic swept the world in an infection known as Slim Disease. In retrospect we can now recognize it to have been the HIV wasting syndrome, what is now recognized as the final stages of AIDS. It has only recently swept the world because needle transmission was nonexistent and travel was limited. As as result, exposure was likely isolated to just a single family or small community. Once that group of infected individuals died, so did the possibility for transmission and infection. 

9) Are there any misconceptions about HIV/AIDS?

One of the biggest misconceptions of HIV is how SIV crossed species to develop in humans. Many individuals suspect it is from having sex with infected primate species. This is not correct. It was actually transmitted by eating the apes that were infected with SIV. In many of the open air markets the blood is not contained and there is very little disinfection. As a result, blood transmission is easily possible and consumption of infected animals or cross-blood contamination is the true source of the species jump from SIV to HIV. 

We'd like to give a special thanks to Dr. Nemechek for sharing all this valuable information with us and showing us around the facility. The time was greatly appreciated.

- Kelsey and Amber

Information about HIV/AIDS

As reported by the Mayo Clinic and the U.S. Government HIV/AIDS information, the acquired immunodeficiency syndrome (AIDS) is both chronic and life-threatening, an illness caused by the human immunodeficiency virus (HIV). HIV disrupts your body’s ability to fight off other disease-causing viruses, bacteria, and fungi by slowly killing or damaging the white blood cells of the immune system. It also makes your body more susceptible to certain cancers and other infections a healthy person could resist and/or recover from such as pneumonia. AIDS is the term used to describe final stage of HIV infection. When a person reaches this point in the infection, the virus has weakened the immune system to such an extent that the individual has one of more infection, difficulty fighting off additional infections, and a low count of white blood cells. There is not yet a cure for this disease and because it is life-threatening, preventing transmission is crucial.