Stats and Review

Our service learning project was dedicated to contributing research power to the Fight AIDS at Home project in conjunction with the first World Community Grid project.  The Fight AIDS at Home project is determined to use the computational power to research new drugs that have the correct shape and chemical characteristics to block the HIV protease.  These blockers, called "protease inhibitors", are a way of avoiding the onset of AIDS and prolonging life.  It was cool to see how we were contributing to scientific research with the extra processing power from our computers.  Our BOINC grid completed 412.87 units of work over the semester.  We enjoyed doing this service learning project, especially when we got to meet with our expert, Dr. Carole McArthur.  Being given the opportunity to ask her questions about her dedication to research to HIV and working with people in Africa to fight AIDS was an amazing experience.  Hearing her stories helped apply what we were discussing in class and the ability of HIV to mutate and evolve to become AZT resistant with what we were learning in class.  It’s incredible to see how just by simply running a program behind the scenes of your computer you are contributing to top of the line medical research.  Grid computing makes it very easy for everyone to get involved with the latest scientific research and was a great way for us to relate everything we learned in class with the world around us.  

HIV Response Questions

The following questions below address the Phil. Trans. R. Soc. B. paper entitled “The Evolution of HIV-1 and the Origin of AIDS” by Sharp and Hahn, 2010.  These questions encouraged us to look further into the origin of the HIV virus and how it has evolved over time.

1. What is phylogeography?  How were the authors able to use phylogenetics and phylogeography to localize the origin of HIV strains?
   Phylogeography is the study of the historical processes that may be responsible for the contemporary geographic distribution of individuals. This is accomplished by considering the geographic distribution of individuals in light of the patterns associated with a gene genealogy. The authors were able to localize the origin of HIV strains by relating the virus to SIVs, which is the virus from non-human primates. Through phylogenetic analyses, the HIV strains were divided up into various groups, which were mixed among the SIVsmm lineages. Through this process they traced the source of HIV strains to a virus infecting the central subspecies of chimpanzees in a remote area in the southeast corner of Cameroon.
   

2. How do they know that most HIV transmissions are intraspecific?  Explain.

Most HIV transmissions are confined to members of the same species. This is based on the ways it can spread. HIV can only be passed through blood, bodily secretions or breast milk of an HIV-infected person therefore usually, but not limiting the spread of HIV, to within species. (source: CDC--HIV Transmission)

3. What do the env, vpu, and nef genes code for in HIV?  Would you then expect high levels of mutation rates to be tolerated in these genes? All of these genes code for accessory or structural proteins. Env, which stands for envelope, codes for a surface protein that enables the host cell to attach itself to the CD4 receptors present on the lymphocytes. Vpu is a integral membrane phosoprotein, which has many functions in the virus. It is responsible for CD4 degradation, as well as helping to release virions from infected cells. The Nef gene codes for a membrane associated phosoprotein. It also plays a role in the replication cycle of the virus and plays a role in cell apoptosis and in the virus’ ability to infect. One would expect very high levels of mutation in these genes because they deal with mostly replication and infection of new target cells. This is the main problem that researchers are dealing with when battling HIV. The virus is always finding novel ways to infect, replicate and find new target cells, while staying one step ahead of the researchers and their treatments.
4. Apply Darwin’s postulates to the adaptation of the recombinant virus to the human host population.

The origin of the HIV virus

Darwins postulates applied to HIV adaptation:

Variation: There are at least 12 known transmissions of SIV’s to humans, with hundreds to thousands of years of opportunities for this virus to have jumped back and forth between the chimpanzee-monkey- human hosts and vice versa. This has resulted in a large amount of variation within the virus itself: HIV-1 group M (most common form) has anti-CD4 activity and anti-tetherin activity, group N has only anti-tetherin activity, and group O has only anti-CD4 activity.

Variation is heritable: In order for these variations to spread and get passed onto offspring they must be heritable.  These variations can be traced back to the ancestral form, SIVcpz virus and its inability to act against human tetherin. The transmission of SIV to human hosts occurred on three separate occasions from different ape species, resulting in various heritable adaptations amongst the virus groups to infect human hosts. The anti-CD4 activity was conserved from the ancestral SIV virus.

More offspring produced than able to survive: Many viral forms jumped from populations from ape to human host over the last thousand years, and only those well adapted to infect humans have remained. The HIV-1 group M, which accounts for perhaps 98% of HIV infections, has fully successful mutations to combat tetherin and CD4 activities resulting in the high rate of fitness of the virus.

Adaptation leads to evolution of the population: The transition of SIV to HIV resulted in selection pressures on the viral populations once transmitted from ape-human host. This pressure resulted in some strands of the virus to mutate in order to effect the human hosts more efficiently. This lead to those strands becoming more dominant in the population and to the evolution of the virus.

5. What evidence does this study provide that we share an immediate common ancestor with Pan troglodytes?

Chimpanzees, Pan troglodytes, and humans are genetically very similar, as they are the two closest related species in the ape family. Chimpanzees were most likely infected by the SIV virus known to infect the red-capped mangabeys monkey population, which is also native to the west central Africa region where HIV-1’s ancestral form is thought to have originated. Similarly to the mutations brought about by the selection pressures in the transition from ape-humans, the mutations from the ancestral monkey form of SIVs to the current ape/chimpanzee form SIVgor are thought to have been due to the recombination of two separate viral strains of SIV. HIV-1 group M, the main form of AIDS infecting humans, has been traced back to SIV in chimpanzees, Pan troglodytes, in addition to other forms such as HIV-1 groups N, O, and P.

6. Refer to Figure 1 which has been copied from the paper 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.

Figure 1

Based on the diagram, shown in Figure 1, the allegations from the patients found within the dental clade are believed to be correct.  Patients A, B, C, E, and G are all found within the dental clade and all had a similar strain of HIV to that of the dentist.  These patients would have gotten the virus from their dentist because they all share a similar HIV sequence with the dentist.  Though HIV has a high rate of mutation, somewhere between the frequency of 10-8 and 10-4, the genome can still be sequenced and tested for similarities with the original strain coming from the dentist (Mansky).  The x’s and y’s found in Figure 1 represent different mutations within the HIV virus.  Since the patient’s HIV sequence more closely resembles that of the dentist than the local controls, they must have contracted the same strain of HIV that originated from the dentist.  However, patient’s D and F, not found within the dental clade, did not contract HIV from their dentist.  The strains of the HIV virus found in patients D and F resemble the strains also found in the local controls, labeled by LC in Figure 1.  Since the strains from the local controls and these patients are more closely related in the phylogenetic tree they would have received the virus from an alternate source than the dentist.

By looking at the different sequences of the genomes in each person who tested positive for the HIV virus, phylogeneticists are able to piece together the pathways the virus took and which people actually contracted the virus from the dentist.  There are several methods of constructing a phylogenetic tree including Neighbor Joining Method, Parsimony, Genetic Distance Method.  In the case of the dentist, the Neighbor Joining Method would compare two patients or compare the dentist to the patient’s HIV sequence and run an algorithm to determine if the two subjects had a small yield.  A small yield between the two would allow the phylogeneticists to determine they were neighbors and they would be joined in the phylogenetic tree.  This tree shows the relationships between the patients and allows the tree to be created based on the similarities in the HIV sequences (Li.) Parsimony involves creating a tree that has the simplest evolutionary explanation with the fewest conjectures or nodes in the tree (Li).  The simplest tree created by this method replicates the evolutionary changes and mutations the virus underwent and shows how it was most likely transferred from one person to another. The Genetic Distance Method also uses an algorithm and weighs the differences in the HIV strain according to how closely the strains can be related (Li).  Genetic analysis helps determine how similar or different the strains are.  This was most likely used to see which strains were more similar to the dentist than to the local controls.  It is to my understanding that the Parsimony method was used to construct this phylogenetic tree since it is the most commonly used tree and it most accurately displays the evolutionary pathway of the HIV virus. References:

Li, Yan. "How to Build a Phylogenetic Tree." 489 Bio. N.p., n.d. Web. 5 Apr. 2014. <http://guava.physics.uiuc.edu/~nigel/courses/598BIO/498BIOonline-essays/hw2/files/hw2_li.pdf>.

Mansky, Louis M.Louis M. . "Retrovirus mutation rates and their role in genetic variation." Journal of General Virology. Version 79. N.p., n.d. Web. 6 Apr. 2014. <http://vir.sgmjournals.org/content/79/6/1337.short>.

AIDS Research Interview

AIDS Interview 

This week we have had the opportunity to interview two amazing women who have first hand experience in helping deal with the current struggle against HIV and AIDS.  Both Dr. Maithe Enriquez and Dr. Carole McArthur are associated with UMKC and shared incredible insight with us on what the disease is, how it is affecting the world around us, and how we are looking to find a cure.   

Dr. Maithe Enriquez currently has a clinical appointment at the UMKC School of Medicine and provides primary care to adults living with HIV disease in the Infectious Disease clinic.  She has a rich background in dealing with HIV as she is currently a principal investigator for an NIH funded study focused on addressing non-adherence to HIV treatment in the community.  HIV or Human Immunodeficiency virus is a retrovirus that selectively infects CD4 cells, a white blood cell, and T-cells that are critical for cell-mediated immunity. Overtime untreated HIV progresses and destroys the immune system causing Acquired Immune Deficiency Syndrome also known as AIDS.  AIDS compromises the immune system making the affected person susceptible to infections and other diseases that they can’t fight off.  

HIV is a virus passed from person to person through sexual fluids and blood.  20 years ago, blood transfusions were the main means of transportation of HIV and knowing how HIV is transferred has since helped us attempt to maintain the virus.  Making sure the public is aware of how to stay safe from contracting this virus is an important job.  Not sharing hypodermic needles, blood, or bodily fluids with someone who is HIV positive is a prime way to avoid contracting the virus.  “No one has to get AIDS anymore,” Dr. Enriquez tells us, “given the availability of efficacious treatment.”  Early detection of HIV can help prevent the disease from progressing into AIDS.  If someone does test positive for HIV, treatment has advanced to the availability of regimens that are one pill a day (3 medications combined in 1 pill).  This one pill regimen could help prevent million of people from advancing the HIV disease into AIDS.  According to the AIDS web site, AIDS.gov, 3.4 million people are currently living with HIV/AIDS worldwide and 97% of these people live in low to middle-income countries where treatment is difficult to find and afford.  This epidemic has caused more than 25 million deaths since it was first discovered in 1981 and more than 1.4 million people in the United States are living with the HIV infection putting them at risk for AIDS.  

A world map showing how many people are infected with HIV (Global Statistics).

So what does this mean for these 34 million people?  HIV/AIDS research has been working on finding a cure for more than 30 years and Dr. Enriquez is optimistic.  Though HIV is a difficult disease to pinpoint a cure for due to its ability to multiply rapidly and to adapt over time, researchers are making strides in attempting to find a cure and to keep up with its ever changing nature.  We asked Dr. Enriquez if she thought finding a cure to HIV/AIDS is in the near future to which she responded “I think yes, an effective cure will be developed.”  This is good news for the the 34 million people around the world who are suffering from HIV/AIDS and for the projected (on average) 2 million people who contract the disease for the first time each year according to AIDS.gov.  “It’s amazing to me to have witnessed how much HIV treatment has advanced!” says Dr. Enriquez who has played an important role in the advancement of HIV/AIDS knowledge in communities as well as in the discovery of treatments for the disease.  Dr. Enriquez also encouraged us to watch the critically acclaimed documentary “How to Survive a Plague” about the AIDS epidemic.  The official trailer to the documentary is included below.

The official trailer for the documentary "How to Survive a Plague", which has received outstanding reviews and is highly recommended for anyone looking to learn more about the spread of HIV/AIDS in America. The film is available on Netflix.

We also had the pleasure of meeting with Dr. Carole McArthur last week at Michael Forbes restaurant in Brookside.  Dr. McArthur is very knowledgeable in how to take care of people who are suffering from HIV or AIDS and also the process that is being observed in order to find an effective cure.  Dr. McArthur shared with us a little bit about her background and how she came to know so much about the disease.  Dr. McArthur received her P.h. D. from Otago University in the South Island of New Zealand and then performed her post-doctoral work at the University of Florida, where she also ran track at the University of Florida for the Florida Track club team. By this time, Dr. McArthur had become an expert in genetic monoclonal antibody research, a fairly new field at that time, and was recruited by a researcher at Scripps Research Institute to do more post-doctoral work, immediatley  moving to Michigan to do research at Michigan State University. At Michigan State she was spear-heading the collaboration of industry and science in academia, one of the first experiments  in American history, creating create many new medical devices and advances that we still use today.  She then progressed to work for Abbott Laboratories in Chicago, focusing on genetic engineering, working amongst an R and D department with 22,000 scientists who were “very brilliant people!” she exclaimed. After all these years of research Dr. McArthur then decided to attend UMKC to get her M.D. in pathology and became a doctor.  Dr. McArthur now works at Truman Medical Center helping patients with HIV and also teaches immunopathology in school of dentistry at UMKC, which led us to meeting her for this interview.  She has an extensive background in researching HIV and similar diseases and also handling and controlling diseases in the community.  Dr. McArthur has also been to Cameroon, Africa, taking along medical supplies and equipment to set up a lab where she helps educate and treat people in Africa with HIV.  Dr. McArthur has an extensive background in HIV/AIDS treatment and was a perfect match for us to interview. 

Dr. McArthur (center) educating the local people in Africa on HIV.

When asked to describe AIDS in her own words Dr. McArthur used a house of cards metaphor; the HIV virus completely attacks the immune system similar to the removal of a bottom card in a house of cards, just as the house of cards would collapse upon itself, so does the immune system and body when infected with HIV.  This collapse of the immune system leaves the person open to contracting other infections such as Tuberculosis.  Dr. McArthur said that almost all the patients who had hemophilia and received blood transfusions contracted HIV and died from AIDS and other complications during the 1980s when testing was less robust than today.  A high percentage of hemophiliacs suffered from not only HIV-1 but also the hepatitis C virus that was transmitted through blood  also (White).  According to Dr. McArthur, there are several common misconceptions about HIV and AIDS in the general population. One such misconception is the virus’s ability to live outside of a human host, which it is not able to do for very long at all.  The HIV virus needs a host cell to live off of in order to survive.  Another, more prevalent misconception has to do with the pathogenicity of the virus.  HIV must be introduced directly to an open wound, or through various body fluids, and therefore in comparative terms, is really not as infectious as some other common diseases. Dr. McArthur used the following image to demonstrate the potency of the infectious capabilities of HIV in contrast to those of Hepatitis B. Imagine there is a spoonful of HIV (for all intents and purposes) in a pool, no one would get it unless they had an open wound, but if there is a spoonful of Hepatitis B, then every swimmer would be infected. Research has made huge advances in the last several years, trying to find a cure and ways to confine the HIV virus and limit the number of people who have to live with AIDS.  HIV is also not as lethal as it once was, as now there are many more medications out there to postpone symptoms.  

Many different strains of HIV can be localized all over the world.

Dr. McArthur believes the search for a cure for HIV to be critical, and believes it is completely obtainable. The difficulty in finding a cure arises in the virology of HIV, with its fast mutation rate, numerous different strains and issues of drug resistance, as well as the more often deadly, opportunistic infections and diseases, such as Tuberculosis, that prey on the weakened immune system.  Several different strains of HIV can be seen in the image below and researchers are attempting to document the changes and movement of different strains across the globe to better understand the virus.  Dr. McArthur has also helped begin trials in Africa on different types of drugs that can be used to prevent or cure HIV.  However, finding a drug that will cover the vast array of strains and quick mutations of HIV is a work in progress.  Above all else, Dr. McArthur believes the main obstacle to developing a cure to HIV/AIDS lies in the money. “It’s just money, that’s what it is. If we solve this problem, we’ll solve so many other diseases. It is just a matter of time. Look at cancer—no one said we would find a cure and now there are so many cancers that are curable.”  It is true that with several cures for common cancers we can see a light of hope at the end of the battle against the HIV/AIDS pandemic.

Acknowledgments:
We would like to extend a generous thank you to both Dr. Maithe Enriquez and Dr. Carole McArthur for helping us with this project and for sharing so many great stories with us! They are truly experts on HIV and AIDS and helped us understand the magnitude of this disease and how important it is to help find a cure.

References:

"Global Statistics." AIDS.gov. U.S. Department of Health & Human Services, n.d. Web. 6 Feb. 2014. <http://aids.gov/hiv-aids-basics/hiv-aids-101/global-statistics/index.html>.

"HIV/AIDS." National Hemophilia Foundation. N.p., n.d. Web. 14 Feb. 2014. <http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=43&contentid=39>.

Picture References:
 
http://dentistry.umkc.edu/oralbio/faculty/mcarthur_cameroon.shtml
http://aids.gov/hiv-aids-basics/hiv-aids-101/statistics/
http://www.pbs.org/wgbh/pages/frontline/aids/atlas/clade.html
http://aids.gov/hiv-aids-basics/hiv-aids-101/what-is-hiv-aids/

Grid-Computing Project--AIDS

Intro—grid-computing

http://www.personal.psu.edu/afr3/blogs/SIOW/2011/10/good-news-for-hiv-victims.html

         I have never heard of the term “grid-computing” before entering college. More specifically, not until enrolling in Evolution at Rockhurst University.  I went straight to Google to try to get a grasp of what my teacher (Dr. Walker) was talking about. Grid-computing is a form of networking that incorporates many devices by using unused processing data to solve problems that would be improbable for a single machine alone (webopedia). Now that sounds strange. How can a software be able to harness the power from multiple computers and use it to help advance the research for diseases? And perform all this safely?  As Dr. Walker kept talking of the subject of grid-computing, it became more and more realistic. In order to become part of the grid-computing community, we (Kasey, Margaret, Nick and Hilary) had to download and run a software from a grid projects website. We chose the topic of AIDS. By downloading and running this software, we are giving more resources in order to grow the network to help advance the research of AIDS.

What is AIDS?

http://www.rkm.com.au/VIRUS/HIV/HIV-virus-life-cycle.html

                AIDS, or acquired immune deficiency syndrome, means the body has adopted or developed over time a shortage in the immune system. According to the AIDSinfo, via  the NIH the definition of AIDS, a disease of the immune system due to infection with HIV.  Since Aids develops over time it must begin from somewhere, right? This is why we must understand the human immunodeficiency virus (HIV). HIV destroys the CD4 T lymphocytes (CD4 cells) of the immune system, leaving the body vulnerable to life-threatening infections and cancers. Acquired immunodeficiency syndrome (AIDS) is the most advanced stage of HIV infection. 

Conclusion

Currently there is no cure for people suffering with aids. For now it can be controlled through proper medical care with the use of antiretroviral drugs (CDC). These make it harder for HIV to copy itself and infect other CD4 cells.  Therefore, slowing down the process, allowing the body to fight off infection by making more CD4 cells. We have come a long way and grid-computing is another piece of the puzzle to advance our research and eventually find a cure.

HIV rap..

Works Cited

www.webopedia.com/TERM/G/grid-computing.html

http://www.nlm.nih.gov/medlineplus/ency/article/000594.htm

http://www.cdc.gov/hiv/basics/index.html

http://www.aidsinfo.nih.gov/education-materials/glossary/3/acquired-immunodeficiency-syndrome