BIOL368/F14:Chloe Jones Week 3

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Annotated Bibliography for HIV Evolution Project


  1. Write three questions (or more) that you have about HIV that you would like answered.
    1. When does HIV become AIDS?
    2. If somebody infected with HIV has blood that touches you and you unknowingly tough your eye or nose, would you contract the disease?
    3. Does HIV impact your opportunity to receive employment?
  2. Keyword Search
    1. What original keyword(s) did you use? How many results did you get?
      • Web of science: HIV(264,797 results) ENV gene (4,310)
    2. Which terms in which combinations were most useful to narrow down the search? How many results did you get after narrowing the search?
      • HIV+ENV gene: 2,305
      • HIV+ENV gene+CD4 T: 411
      • ENV gene+CD4 T: 483
      • When I added CD4 T it narrowed the results down dramatically taking the articles available from 2,305 to 411.
  3. Advanced Search - For all three, which advanced search functions were most useful to narrow down the search? How many results did you get?
    1. Web of Science
      • Using the topic: HIV-1 and ENV gene ( 1,985 results)
      • Using the topic: HIV-1 and ENV gene Author: Markham (2 results)
      • Results were able to be narrowed by incorporating an author and using the term AND to include all topics that I wanted discussed in the article. Also, by choosing the years and how many times an article had been cited allowed me to find recent articles as well as articles that seemed noteworthy to others.
    2. PubMed
      • (Hiv-1[Title/Abstract]) AND ENV[Title/Abstract] (4323 results)
      • ((HIV-1[Title/Abstract]) AND ENV gene[Title/Abstract]) AND CD4[Title/Abstract] (137 results)
      • By immediately clicking the advanced button it allows you to search using keywords found in the title and the abstract which I thought was extremely helpful. Also, by clicking the free full it allowed you to see which ones that had available.
    3. Google Scholar
      • HIV-1 and env gene: (100,000 results)
      • HIV-1 and env gene and CD4-T (31,600 results)
      • HIV-1 and env gene and CD4-T and author: Markham (2,080 results
      allintitle: env gene and HIV-1 (68; results)
      • To decrease the results in Google Scholar The drop down tool was essential because it allowed you to search keywords in the title, and or use an exact phrase. Also, allowed words to be excluded and for the time it was published to be taken into account
  4. Prospective Search on Markham et al. (1998)
    • Markham et al. (1998) cited 51 articles
    • Markham et al. (1998) has been cited 70 times


Primary Research Articles

  1. Ince WL, Zhang L, Jiang Q, Arrildt K, Su L, Swanstrom R. Evolution of the HIV-1 env gene in the Rag2−/− gammaC−/− humanized mouse model. J Virol 2010;84:2740–52
  2. Ensoli B, Bellino S, Tripiciano A, Longo O, Francavilla V, et al. (2010) Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART. PLoS One 5: e13540. doi: 10.1371/journal.pone.0013540
  3. Garcia-Arriaza J, Najera JL, Gomez CE, Tewabe N, Sorzano CO, Calandra T, Roger T, Esteban M. 2011. A candidate HIV/AIDS vaccine (MVA-B) lacking vaccinia virus gene C6L enhances memory HIV-1-specific T-cell responses. PLoS One 6:e24244. doi:10.1371/journal.pone.0024244.

Review Article

  1. Ince et al., 2009 W.L. Ince, P.R. Harrington, G.L. Schnell, M. Patel-Chhabra, C.L. Burch, P. Menezes, R.W. Price, J.J. Eron Jr., R.I. Swanstrom Major coexisting human immunodeficiency virus type 1 env gene subpopulations in the peripheral blood are produced by cells with similar turnover rates and show little evidence of genetic compartmentalization J. Virol., 83 (2009), pp. 4068–408

Preparation for Week 4 Journal Club


  1. Chemostats : (n.) An apparatus in which a bacterial population can be maintained in the exponential phase of growth by regulating the input Source: Oxford Dictionary of Biomedicine
  2. Epitope (n.) The antigenic determinant on an antigen to which the paratope on an antibody binds.Source: Oxford Dictionary of Genetics, 8ed
  3. Hypervariable (region): (n.) Any region of a coding sequence that exhibits high variability. This occurs e.g. in viral genes encoding coat proteins. Source: A Dictionary of Biomedicine
  4. Intravenous : (adj.) into or within a vein. Source: Oxford Concise Medical Dictionary, 8ed
  5. Monophyletic : (adj.) describing an number of individuals, species, etc., that have evolved from a single ancestral group Source: Oxford Concise Medical Dictionary, 8ed
  6. Nonsynonymous (adj.) A nucleotide substitution in a codon which results in a change of the amino acid encoded.Source: Oxford Dictionary of Ecology, 4ed
  7. Seroconvert : (v.) To produce specific antibodies in response to the presence of an antigen e.g. a vaccine or a virusSource: Oxford Dictionary of Dentistry
  8. Seronegative : (adj.) giving a negative result in a test of blood serum e.g. for the presence of a virus.Source: Oxford New Zealand Oxford Dictionary
  9. Synonymous: (adj.) Two or more nucleotide triplets that code for the same amino acid. For example, UUU and UUC are synonymous codons. Source: A Dictionary of Genetics, 8ed
  10. Virologic/ virology : (n.) The scientific study of viruses and the diseases caused by them. Source: Oxford Dictionary of Biochemistry and Molecular Biology, 2ed

Article Outline

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

I. Abstract

A. sequence diversity or divergence from producing antibodies more shown in progressors, than nonprogressors
  1. progressor=nonsynonymous mutations
  2. nonprogressors=selected against nonsynonymous mutations, fear of resulting in virus with greater strength to replicate
B. No predominate variable
  1. Evolution of dominate variable to similar type
C. Looking at the level at which CD4-T cells fall, provide the number and the different type which allow for the best adaptation to host
D. Previous Studies
  1. only examined small group
  2. did not analyze direct sequence patterns of subjects
  3. not enough check points for subjects, over a time span

II. Introduction

A. In stable environment there would be a dominant virus, and minimal mutations not really represented
B. Destabilizing would have a new dominant force, with the ones who recently were dominant, are now the minority
  1. Immune response only attacking most abundant, minority pop continue to mutate and grow
C Studying patterns of diversity can provide information on the virus and its ability to adapt

III. Methods

A. The Study Population
  1. Sequences of env were studied in 15 participants based on what rate there CD4 T cell count dropped. Studied from point of seroconversion, point at which antibodies introduced. 6 month interval check-up
  2. Groups defined based on level of CD4 T cells
a.) Rapid Progressors= fewer than 200 CD4 T cells within 2 years of contracting
b.) Moderate progressors= declined to 200–650 during 4 years
c.) Nonprogressors= maintained CD4 T cell levels above 650 during observation period
B. Sequencing of HIV-1 env Genes
  1. PCR used to amplify env gene from peripheral blood mononuclear cells (PBMC).
a.) studies how viral DNA found in great numbers in inactivated PBMC, which is the form that it is in most humans hasn’t been integrated into host genome
b.) From the primers the restriction sites BamHI and EcoRI were used for cloning purposes
c.) Amplified sequences, 5 samples at the lowest level choose for 2nd round of PCR. Already had 126 input copies of viral DNA from initial round.
C. Plasma Viral Load
D. Generation of Phylogenetic Trees.
E. Correlation Analysis
  1. Study the connection between genetic diversity and divergence
a.) X0= diversity, or mutational divergence , Y0= CD4 T cell count
F. Determination of dS/dN Ratios
  1. Difference between the strains were labeled as synonymous (dS) or non-synonymous (nS)
a.) Changed because based it on where mutation could occur, remove bias of unequal sample sizes
G. High Genetic Variation in subjects 9 & 15
  1. Study to see if infected with two different viruses. Phylogentic tree contructed.
  2. HIV-1 seronegative 7 months before 1st visit
  3. Exclusion of subject 15; diversity higher
H. Comparison of the Rate of Change of Divergence and Diversity
  1. Divergence vs. Diversity over time

IV. Results

A. CD4 declinig rates variable amongst subjects
B. Focused on viral env region: interested in this site because it is where the host and virus interact and it endures numerous mutations.
C. PCR. Sequences studied based on two factors: genetic diversity, and divergence
  1. diversity:differences of nucleotide between the clones during that visit
  2. divergence:change in nucleotides from one visit to the next
D. Diversity and divergence increased amongst groups
  1. Order (most-least) : Rapid progressor, moderate progressor, non-progressor
  2. Moderate progressors and rapid progressors were not able to show diversity through p-values
E. If Diversity and divergence increased CD4 T cell count decrease
F. Evolution in non-progressor show that not beneficial for viruses to carry changes in envelope structure
G. If favored NS changes then considered a nonprogressor, allows the differentian of progressors versus non-progressers .
H. No single stain showed predominance .
I. Figure 1: Figure 1 shows how the diversity and divergene of the 15 subjects changed since the first servopostive visit. The graph is broken up into categories of:Rapid Progressors, Moderate Progressors or Non-Progressor. From this graph we can infer that amongst the groups the rapid progressors had the most crucial slope for CD4 t cell decline. For diversity and divergrance it was variable with it increasing mainly in the progressor groups.
J. Table 1: Table 1 shows the data taken from the visits by the subjects. The data shows that the more active the disease (i.e. progressors) the more diversity and divergence you are going to have as well as a more rapid decline in CD4 T cell count.
K. Figure 2: Figure 2 shows the mean slope of diversity and divergence within each group. The rapid progressors show the most amount of diversity and divergence, with the moderate progressors following in 2nd, and the non-progressors showing minor changes.
L. Figure 3: Figure 3 examines the phylogenetic tree from subject 9. The study of subject 9 showed that viral isolates were similar to a virus observed in the first visit.
M. Figure 4: Figure 4 examines the phylogenetic tree of 4 random participants in the study. Studying the phylogenetic trees allow the reader to see how a virus has limited progression along a single branch and then returns to a previous strain that has already been observed.

V. Discussion

A. Higher levels in genetic diversity and divergence correlated to a greater decline in CD4 T cells
  1. Subjects with similar CD4 T cell count, but different diversity were studied and the participants with more diversity had a CD4 T cell count that decreased more rapidly.
B. Conflicting results with recent studies
  1. McDonald et al.
a.) Agreed: rapid progressers had greater genetic diversity, however they didn’t have as much diversity as slow progressors for the 2nd vist
b.) Diversity differed depending on what ENV region selected ( C2–C5 or the C2–V3)
  1. Wolinsky et al.
a.) Subjects with rapid CD4 T cell decline, had less genetic diversity; subject could have been exception
C. Participants who advanced to AIDS had an increase in diversity and divergence
  1. Virus that was dominated initially, no longer as dominant as progression continued
D. Immune response only focusing on a particular site, targeting the most frequent viruses, therefore not killing the viruses as a whole
E. Nonsynomous mutations favored because allows virus to be more easily recognizable by host cell
  1. Observed in Nonprogressors

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Chloe Jones 03:46, 15 October 2014 (EDT)Chloe Jones