Our group used the not for profit program rosetta@home to fold proteins that could one day help find cures for many different diseases, such as HIV. From this project, we have learned that HIV is a disease that is tricky to understand due to it's ability to mutate rapidly. Grid computing is an important process that may one day help us to better understand the mutations in the HIV strands. It is also important to research the evolution of HIV in order to understand how it has previously mutated, and how it is becoming resistant to treatments. It became clear to us how important it is to study the evolution of HIV when we visited the blood bank. How fast and often certain strands mutate is information that is necessary in order to keep blood transfusions safe.
Total units: 6,487
Average units: 74.88
Manager: BOINC
Thursday, April 28, 2011
Friday, April 22, 2011
Response to HIV Questions
1. HIV evolves rapidly, and the transcriptase enzyme that is necessary for replication is very prone to mutation. Mutation is a positive aspect in this study when it comes to being able to trace when the disease was spread. If two strands in separate individuals are similar (and from the same source), this would indicate that the transmission of HIV was recent because the strand has not yet had time to mutate. HIV's fast mutation rate is problematic when we are looking at developing interventions and effective treatments; however, when tracking it epidemically, it is useful to know which sequences of HIV are likely to mutate rapidly and which are likely to be conserved. That way, we can compare these sequences between individuals and determine whether or not there exists an epidemiological connection.
2. The env segment codes for the protein gp160, which eventually in the life cycle of HIV is transformed into the two proteins gp120 and gp41. Gp120 serves as the main binding site for CD4 receptors on target cells of the HIV virus. The main function of the pol gene is that it codes for the reverse transcriptase protein of HIV; the protein that enables its backwards RNA to DNA copying. Pol also codes for the proteins protease, RNAse H, and integrase. The gag gene in HIV codes for four separate proteins which make up the viral core: p24, p17, p9, and p6.
The gene env mutates very rapidly, while the gene pol is highly conserved. These genes differ in their mutation rates because they have different tolerances for mutation based on their unique sequences of amino acids. Since some amino acids have multiple codons, mutations in these specific amino acids can be tolerated more frequently because it doesn't alter the overall effectiveness of the gene. So apparently env is highly redundant in its amino acids in that a lot of them have multiple codons, whereas the amino acids that make up pol are not as flexible and thus do not tolerate mutation as much. When mutations do occur, the gene is most likely lost. Therefore, the pol genes that are functional in the HIV viral strain are the ones that have remained highly conserved.
The researchers of this study chose to sequence gag and env because although env evolves very rapidly, similarities can still be detected if the period between transmission and testing is very short. The gag gene is most effective for determining epidemiological relationships when studied alongside the env gene. They chose not to sequence the pol gene because although it is a gene that undergoes relatively few mutations in the HIV strand, gene sequences for pol can appear to be very similar even between unrelated strands of HIV.
2. The env segment codes for the protein gp160, which eventually in the life cycle of HIV is transformed into the two proteins gp120 and gp41. Gp120 serves as the main binding site for CD4 receptors on target cells of the HIV virus. The main function of the pol gene is that it codes for the reverse transcriptase protein of HIV; the protein that enables its backwards RNA to DNA copying. Pol also codes for the proteins protease, RNAse H, and integrase. The gag gene in HIV codes for four separate proteins which make up the viral core: p24, p17, p9, and p6.
The gene env mutates very rapidly, while the gene pol is highly conserved. These genes differ in their mutation rates because they have different tolerances for mutation based on their unique sequences of amino acids. Since some amino acids have multiple codons, mutations in these specific amino acids can be tolerated more frequently because it doesn't alter the overall effectiveness of the gene. So apparently env is highly redundant in its amino acids in that a lot of them have multiple codons, whereas the amino acids that make up pol are not as flexible and thus do not tolerate mutation as much. When mutations do occur, the gene is most likely lost. Therefore, the pol genes that are functional in the HIV viral strain are the ones that have remained highly conserved.
The researchers of this study chose to sequence gag and env because although env evolves very rapidly, similarities can still be detected if the period between transmission and testing is very short. The gag gene is most effective for determining epidemiological relationships when studied alongside the env gene. They chose not to sequence the pol gene because although it is a gene that undergoes relatively few mutations in the HIV strand, gene sequences for pol can appear to be very similar even between unrelated strands of HIV.
3. Looking at the phylogenetic trees for the gag and env sequences of the Glenochil cohort, we think that the data gives sufficient proof that the source of infection was the same for all individuals because they all share the most recent node, the most recent ancestor of the viral strain. We think that the HIV genes in these prisoners could be accurately described as orthologous because orthologous simply means that the gene sequences are homologous—they share a common ancestor. The phylogenies show this to be very likely on multiple levels (both from the gag sequence and the env sequence).
4. The unrelated HIV strains in this phylogenetic analysis serve as the control group. HIV mutates extremely rapidly, but the researchers wanted to show that even though the individual strains had mutated, the strains in the Glenochil cohort were still more closely related to each other than they were to a “control” strain—or just some other random strain from the HIV population. They utilized a variety of unrelated “control” strains to show that the Glenochil strains were still likely to have come from the same source, even when compared to a variety of other HIV strains.
5. In the past decade, there have been four main measures taken to decrease the spread of HIV in prisons. The first is making bleach available for all inmates. This prevents the use of needles and syringes that are not properly sterilized. The second method is providing clean syringes and needles to the inmates. The provision of clean needles and syringes will prevent inmates from sharing dirty needles. The third mechanism is substitution treatment programs. These programs have proven to lower the amount of drugs being used and the amount of drugs traded. The last mechanism to reduce the spread of HIV is making condoms readily available. These are usually distributed by machines in the facility. Although these four mechanisms do not stop drug use, they make it slightly safer and decrease the spread of HIV.
Some prisons have also introduced voluntary HIV testing and counseling. Like we learned from our interview with Dr. Menitove, our methods for detecting the HIV virus are now a lot more advanced than in the early 90s, so it is much faster and more reliable now to test people for HIV. However, it's been proven that separating the housing of HIV-positive inmates in prisons has not had a significant effect on decreasing the spread of HIV, mainly because inmates are still gathering and potentially infecting each other through shared needles or unprotected sex. The measures listed above have given inmates opportunities to be safer, but unfortunately not all prisons make these preventions readily available. Many countries' governments have unfortunately turned a blind eye to the prevalence of injecting drug use and unprotected sex in prisons, so funding for HIV/AIDS education and testing/counseling (along with the other sterilization measures) has been hard to come by. Where these programs have been implemented, only positive changes have occurred in the prisons. It is obvious that the prison communities should be granted all of the same HIV/AIDS prevention and treatment programs that are available to the general population; only then can we hope to see a decrease in the HIV rate among prisoners.
6. According to the phylogenetic tree generated by the researchers for the dental clade of patients infected by HIV, we think the allegations were correct that the dentist was indeed the source of the virus. The authors probably generated this tree in a manner similar to the case of the Glenochil cohort, by comparing certain genes (probably the env and gag) between all the patients/individuals and looking for distinct similarities in the viral strains. The article said that the researchers were able to successfully track down the patients and obtain samples of their HIV strains to compare to the dentist and to each other within 2 or 3 years of the supposed infection date; that had been a short enough period of time for them to notice strong similarities and construct the phylogeny. However, if they had waited longer, their evidence that the dentist was the source may not have been as compelling.
Some prisons have also introduced voluntary HIV testing and counseling. Like we learned from our interview with Dr. Menitove, our methods for detecting the HIV virus are now a lot more advanced than in the early 90s, so it is much faster and more reliable now to test people for HIV. However, it's been proven that separating the housing of HIV-positive inmates in prisons has not had a significant effect on decreasing the spread of HIV, mainly because inmates are still gathering and potentially infecting each other through shared needles or unprotected sex. The measures listed above have given inmates opportunities to be safer, but unfortunately not all prisons make these preventions readily available. Many countries' governments have unfortunately turned a blind eye to the prevalence of injecting drug use and unprotected sex in prisons, so funding for HIV/AIDS education and testing/counseling (along with the other sterilization measures) has been hard to come by. Where these programs have been implemented, only positive changes have occurred in the prisons. It is obvious that the prison communities should be granted all of the same HIV/AIDS prevention and treatment programs that are available to the general population; only then can we hope to see a decrease in the HIV rate among prisoners.
6. According to the phylogenetic tree generated by the researchers for the dental clade of patients infected by HIV, we think the allegations were correct that the dentist was indeed the source of the virus. The authors probably generated this tree in a manner similar to the case of the Glenochil cohort, by comparing certain genes (probably the env and gag) between all the patients/individuals and looking for distinct similarities in the viral strains. The article said that the researchers were able to successfully track down the patients and obtain samples of their HIV strains to compare to the dentist and to each other within 2 or 3 years of the supposed infection date; that had been a short enough period of time for them to notice strong similarities and construct the phylogeny. However, if they had waited longer, their evidence that the dentist was the source may not have been as compelling.
Subscribe to:
Posts (Atom)