KP Ramirez Week 7: Difference between revisions

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==Article Assignment==
==Article Assignment==
'''Top 10 Definitions'''
'''Top 10 Definitions'''
#Seroconversion: The development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization. Serology (the testing for antibodies) is used to determine antibody positivity.
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#Phyletic : Assess how to denote the evolution of sequential changes in a line of descent, during which one species is altered.
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#Epitopes: An epitope, also known as antigenic determinant, is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or T cells.
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#Phylogenetic: The study of evolutionary relatedness among various groups of organisms, which is discovered through molecular sequencing data and morphological data matrices.
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#Serological: The scientific study of blood serum. In practice, the term usually refers to the diagnostic identification of antibodies in the serum.
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#Hypervariable Region: The region that pertains to immunoglobulin molecules that contain most of the residues involved in the antibody binding sites.
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#Monophyletic: a monophyletic group is a taxon (group of organisms) which forms a clade, meaning that it consists of an ancestor and all its descendants.
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#Epidemiology: is the study of factors affecting the health and illness of populations, and serves as the foundation and logic of interventions made in the interest of public health and preventive medicine.
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#Virology: The study of viruses and virus-like agents: their structure, classification and evolution, their ways to infect and exploit cells for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy.
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#CD4 T Cell: CD4 T Cells recognize antigens on the surface of a virus-infected cell and secretes lymphokines that stimulate B Cells and T cells.
#


===Outline===
===Outline===
'''Introduction'''
*HIV-1 adapts to a rapidly changing host environment
This experiment focussed on 15 individuals separated between the CDT4 T Cell decline. These were further separated into
*#Rapid Progressors
*#Moderate Progressors
*#Non-Progressors
*Ideally in a stable environment the "best fit" virus will be predominate.
*Likewise an unstable environment either variable mutants are selected against or the dominant strain is selected.
*This observes the forces against HIV that cause diversity and look at how the virus is adapting.
'''Previous Studies'''
*Previous studies addressed smaller control groups analyzing smaller number of time points per subject.
Limitations also include not addressing sequence patterns.
'''Methods'''
*15 known injection drug users with varying CD4T Cells were placed into 3 catagories.
*Blood was obtained every six months.
*Amplified 285-bp region of "env" gene from peripheral blood mononuclear cells.
*Phylogenetic trees
*Taxons labels were used to show the time at which the strain was isolated and the replicates used.
*Correlation  Analysis
*Analyzed between genetic diversity and CD4 T Cell count a year as well as mutational Divergence vs. CD4 T cell count.
'''Figures & Table'''
*Figure 1
Indicates the diversity, divergence and cell count for the 15 individuals. Presents the divergence of the viral variance from the initial visit. The CD4 T cell count lay across the vertical axis and presented the separation between the progressors. Presented steady progression for the moderate progressors. Presents an inverse relationship.
*Figure 2
Indicates the "mean slope" of diversity and differences of each progressor category and indicates significant differences. Presented mean slope of genetic diversity and presented that between the non progressors and rapid progressors they suggested being on trend. Possibly could have had more of a conclusion to divergence, however, it allows us to critique wether this was enough data to explain the rapid nature of progression using the measure of diversity and divergence.
*Figure 3
Phylogenetic tree of evolution from subject 9. This is the results of taking viral samples presenting everything from the first visit to the last visit. This presented no predominent strain throughout the entire experiment. There is an x axis of time, each sequence that is different is given a branch. Every node of the tree means that those two where more closely related based on how far apart and how different they are from each other. The clones are all very close the main branch. This specific one was classified as moderate.
*Figure 4
Phylogenetic tree of four other randomly selected subjects (5,7,8,14). Presents no single dominant strain, but "randomly" they showed all of the moderates. 
'''Results'''
*The more genetic diversity of HIV-1 was closer to the rapid decline with CD4 T cell counts.
*Non progressor groups had a low viral load.
*Diversity and divergence was negatively correlated with the CD4 T cell count over a year.
*Phylogenetic trees gave no evidence of predominance over a single strain.
*More diversity and divergence in the rapid and non progressors
'''Discussion'''
* Increase in diversity and divergence in HIV-1 variants led to CD4 decline
* For subjects who contracted AIDS, their diversity and divergence continued to increase
*To control infection, the host cell must control it at an organismal level due to high diversity of virus mutants
* Nonprogressor viral strains showed possible selection against amino acid change, whereas moderate/rapid progressors selected for amino acid change
===Table 1===
*This table separated the 15 individual subjects into progressor categorization based on the lowest level of CD4 Tcell decline attained during the period of observation.
*Patterns of CD4 decline were quite variable among the 15 subjects, with median annual changes in the subjects’ CD4 T cell number ranging from an increase of 53 cells per year to a decrease of 593 cells per year (Table 1). Serum viral load data were available for all subjects from one of the first three visits and ranged from 1,702 to 321,443 copies of viral genomic RNAyml
*Annual changes in CD4, intravisit nucleotide diversity, and percent nucleotide divergence from the first viruses sequenced after seroconversion reflect slopes of regression lines between individual visits. As slopes of CD4 T cell decline were quite variable between visits in the same subject, progressor categorization of subjects was based on the lowest level of CD4 T cell counts attained during the period of observation.
*Although subject 7 had a 392yyear CD4 T cell decline, his CD4 T cell level never fell below 200 and therefore he was included in the moderate progressor group. His movement to the rapid progressor group would not have altered the statistical support for any of the conclusions reached


{{Kevin A Paiz-Ramirez}}
{{Kevin A Paiz-Ramirez}}

Revision as of 11:08, 2 March 2010