CD4 T cell decline and genetic divergence of the HIV-1 env Gene

CD4 T cell decline and genetic divergence of the HIV-1 env Gene

CD4 T Cell Decline Shows No Correlation With Genetic Divergence in the HIV-1 env Gene Colin Wikholm William Fuchs BIOL 368: Bioinformatics Laboratory Department of Biology Loyola Marymount University October 10, 2016 Outline

The env gene is important in the host invasion, immune system evasion, and survival of HIV-1. Markham et al. (1998) found that a greater genetic diversity and divergence of env was associated with rate of CD4 T cell decline in human subjects. We re-analyzed data from the Markham et al. (1998) to look for an inverse correlation between env genetic divergence and CD4 T cell count in select subjects. We found no significant correlation between genetic divergence and CD4 T cell count. Future studies should address the limitations posed by the methods of this study.

Outline The env gene is important in the host invasion, immune system evasion, and survival of HIV-1. Markham et al. (1998) found that a greater genetic diversity and divergence of env was associated with rate of CD4 T cell decline in human subjects. We re-analyzed data from the Markham et al. (1998) to look for an inverse correlation between env genetic divergence and CD4 T cell count in select subjects. We found no significant correlation between genetic divergence and CD4 T cell count. Future studies should address the limitations posed by the methods of this study.

The env Gene is One of Nine HIV-1 Genes The env gene of HIV-1 plays a major role in viral infection of a human host. http://people.mpiinf.mpg.de/~fmueller/thesis/ thesis_mueller.pdf The env Gene Codes for gp160, Which is Composed of gp120 and gp41 http://people.mpiinf.mpg.de/~fmueller/thesis/ thesis_mueller.pdf

The env Gene Codes for gp160, Which is Composed of gp120 and gp41 The gp120 protein and V3 coded for on env are required for CCR5 co-receptor binding and subsequent cell fusion. http://people.mpiinf.mpg.de/~fmueller/thesis/

thesis_mueller.pdf Mutations in the HIV-1 env Gene Facilitate Escape from Host Immune System http://people.mpi-inf.mpg.de/ ~fmueller/thesis/ thesis_mueller.pdf Outline The env gene is important in the host invasion, immune system evasion, and survival of HIV-1. Markham et al. (1998) found that a greater genetic

diversity and divergence of env was associated with rate of CD4 T cell decline in human subjects. We re-analyzed data from the Markham et al. (1998) to look for an association between env genetic divergence and CD4 T cell count in select subjects. We found no significant correlation between genetic divergence and CD4 T cell count. Future studies should address the limitations posed by the methods of this study. Markham et al. (1998) Found Higher env Sequence Divergence and Diversity in Subjects With More Rapid Progression of CD4 T cell decline.

Would there still be a relationship between genetic divergence and CD4 T cell decline if we used different statistical methods to test only the moderate progressors? We predict that CD4 T cell decline would be positively correlated with genetic divergence. Outline

The env gene is important in the host invasion, immune system evasion, and survival of HIV-1. Markham et al. (1998) found that a greater genetic diversity and divergence of env was associated with rate of CD4 T cell decline in human subjects. We re-analyzed data from the Markham et al. (1998) to look for an inverse correlation between env genetic divergence and CD4 T cell count in select subjects. We found no significant correlation between genetic divergence and CD4 T cell count. Future studies should address the limitations posed by the methods of this study.

Subjects 6, 8, 9, and 14 were Analyzed for Having the Highest Number of Visit Data Points 1. Watterson nucleotide diversity, theta (), was calculated using ), was calculated using sequence alignment in Biology Workbench. 2. Phylogenetic trees were constructed for each of the subjects. 3. Diversity was calculated: Divergence = [ (|(), was calculated using 2-), was calculated using 1)/1|)/time ]), was calculated using 1|)/1|)/time ]time ] - Because of limited time and resources, we calculated divergence as proportional change in over time. - Markham calculated divergence as change in nucleotides the seroconverter. from

4. A test for correlation was performed between genetic divergence and CD4 T cell count for consolidated data and by individual subject. Phylogenetic Trees Showed Diversity due to Divergent Evolution Subject 8 Outline The env gene is important in the host invasion, immune system evasion, and survival of HIV-1. Markham et al. (1998) found that a greater genetic

diversity and divergence of env was associated with rate of CD4 T cell decline in human subjects. We re-analyzed data from the Markham et al. (1998) to look for an inverse correlation between env genetic divergence and CD4 T cell count in select subjects. We found no significant correlation between genetic divergence and CD4 T cell count. Future studies should address the limitations posed by the methods of this study. CD4 T Cell Count Was Not Significantly Correlated With Divergence in Individual Subjects

CD4 T Cell Count Subject 6: r=.40, p=.43 (n = 6) Subject 8: r=-.031, p=.95 (n = 6) Subject 9: r=.0055, p=.99 (n = 7) Subject 14: r=.20, p=.63 (n = 8) Divergence [ (|(2-1)/1|)/time ])/1)/1|)/time ]|)/time ]

CD4 T Cell Count Was Not Significantly Correlated With Divergence in the Combined Data (r=.090, n=27, p=.66) Divergence [ (|(2-1)/1|)/time ])/1|)/time ]1)/1|)/time ]|)/1|)/time ]time ] Lack of Correlation was Likely Due to Method Limitations We only analyzed subjects 6, 8, 9, and 14. - Analyzing other moderate progressors would increase sample size and decrease standard error - Including other groups might show more easily

detectable differences between subjects. - Subject 9 had especially high diversity. We did not use the same measure of divergence used by Markham et al. (1998). - Greater time and manpower would allow us to do this in the future. Future studies should include all subjects and calculate divergence as in the original. Recent studies show co-linear increase in genetic divergence and diversity, a plateau, and then possibly a decrease (Merk & Subramaniam 2013).

Summary The env gene codes for gp120, which is important in the host invasion, immune system evasion, and survival of HIV-1. Markham et al. (1998) found increased divergence of the V3 region of gp120 of HIV-1 in subjects with greater rates of CD4 T cell decline. We used tests for correlation to analyze divergence and CD4 T cell decline in four moderate progressors with the most sequence data from the Markham et al. (1998) dataset. We did not find a correlation between CD4 T cell count and the divergence of the V3 region in HIV-1. Other studies have shown co-linear increase and plateau of

diversity and divergence in various pathogens. Future studies should include all subjects of Markham et al. and only alter the statistical test. Acknowledgements Anu Varshneya Mia Huddleston Kam D. Dahlquist, Ph.D. References Evering, T. H., Kamau, E., St. Bernard, L., Farmer, C. B., Kong, X.-P., & Markowitz, M. (201)/1|)/time ]4). Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1)/1|)/time ] envelope.

Retrovirology, 1)/1|)/time ]1)/1|)/time ], 65. http://doi.org/1)/1|)/time ]0.1)/1|)/time ]1)/1|)/time ]86/s1)/1|)/time ]2977-01)/1|)/time ]4-0065-0 Gall, A., Kaye, S., Hu, S., Bonsall, D., Rance, R., Baillie, G. J., Kellam, P. (201)/1|)/time ]3) Restriction of V3 region sequence divergence in the HIV-1)/1|)/time ] envelope gene during antiretroviral treatment in a cohort of recent seroconverters. Retrovirology, 1)/1|)/time ]0, 8. http://doi.org/1)/1|)/time ]0.1)/1|)/time ]1)/1|)/time ]86/1)/1|)/time ]742-4690-1)/1|)/time ]0-8\ Oliver, A., Cantn, R., Campo, P., Baquero, F., & Blzquez, J. (2000). High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science, 288(5469), 1)/1|)/time ]251)/1|)/time ]-1)/1|)/time ]253. Markham, R. B., Wang, W.-C., Weisstein, A. E., Wang, Z., Munoz, A., Templeton, A., Yu, X.-F. (1)/1|)/time ]998). Patterns of HIV-1)/1|)/time ] evolution in individuals with differing rates of CD4 T cell decline. Proceedings of the National Academy of Sciences of the United States of America, 95(21)/1|)/time ]), 1)/1|)/time ]2568 1)/1|)/time ]2573. Mascola, J. R., & Montefiori, D. C. (2003). HIV-1)/1|)/time ]: nature's master of disguise. Nature medicine, 9(4), 393-394. Merk, A., & Subramaniam, S. (201)/1|)/time ]3). HIV-1)/1|)/time ] envelope glycoprotein structure. Current Opinion in

Structural Biology, 23(2), 268276. http://doi.org/1)/1|)/time ]0.1)/1|)/time ]01)/1|)/time ]6/j.sbi.201)/1|)/time ]3.03.007 Mller, F. (2009). Assessing Antibody Neutralization of HIV-1 as an Initial Step in the Search for gp160-based Immunogens (Doctoral dissertation, Universitt des Saarlandes Saarbrcken). Wang, W., Nie, J., Prochnow, C., Truong, C., Jia, Z., Wang, S., Wang, Y. (201)/1|)/time ]3). A systematic study of the N-glycosylation sites of HIV-1)/1|)/time ] envelope protein on infectivity and antibody-mediated neutralization. Retrovirology, 1)/1|)/time ]0, 1)/1|)/time ]4. http://doi.org/1)/1|)/time ]0.1)/1|)/time ]1)/1|)/time ]86/1)/1|)/time ]742-4690-1)/1|)/time ]0-1)/1|)/time ]4

Recently Viewed Presentations

  • developing PARTNERSHIPS  building CAPACITY  supporting STUDENTS  implementing TECHNOLOGY

    developing PARTNERSHIPS building CAPACITY supporting STUDENTS implementing TECHNOLOGY

    Clicker Document . Word Predictor, Pictures . User Preferences Make and Download . CurriculumSETand Learning Grids . Resources . Overview of Today. Introduction to Clicker 6. Explore Clicker Word Processor. Adjusting User Preferences for picture support (if needed) and investigating...
  • WILLI - wm.edu

    WILLI - wm.edu

    History of Herbaria. Due to nature of plant biochemistry (e.g., cell wall, lignin), dried, pressed plants can last for centuries (even millennia)
  • Queries and Lookups Simple Department Form The Simple

    Queries and Lookups Simple Department Form The Simple

    Module Views Module View Looks Like Ordinary Module Module Component API Oracle Designer creates the view for you, when you tell it to. Use MCAPI. Creates DDL for the view The Underlying View The View Based Form Querying Inserting New...
  • Premier League Primary Stars

    Premier League Primary Stars

    Explain that after looking at different types of poetry, including a poem called Try, Try Again , they will write their very own poem about resilience in the style of their choice. They could win a visit to London for...
  • Sampling of Private Wells for Pesticides, Upstate NY

    Sampling of Private Wells for Pesticides, Upstate NY

    The product names are easier to pronounce but we must be generic. ... Concern about cancer, endocrine disruption. Metolachlor much less concern. Atrazine and metolachlor at Sleepy Hollow Lake 2. Atrazine in the 0.2-0.5 range many samples. Metolachlor up to...
  • Clinical Trials Registration OHSU Knight Cancer Institute Oregon

    Clinical Trials Registration OHSU Knight Cancer Institute Oregon

    What happens if you don't register? Final Rule (42 CFR Part 11) expands regulatory requirements in accordance with FDAAA 801. establishes penalties including civil monetary penalties (up approx$11k/day) and, for federally funded studies, the withholding of federal grant funds
  • Slow Scan Television SSTV - QSL.net

    Slow Scan Television SSTV - QSL.net

    Slow Scan vs Fast Scan. Slow scan is sending an audio signal with the information embedded. Similar to a FAX. Fast scan is a wide bandwidth rf signal (Wider than the 2 Meter band) similar to broadcast TV. We will...
  • Service Evaluation Toolkit for Health and Social Care

    Service Evaluation Toolkit for Health and Social Care

    A useful process for planning your evaluation is to develop a "theory of change" for your service. This can be useful way of articulating and providing a visual representation of the links between the various activities of service and how...