Immunological and clinical manifestations of natural and treated human immunodeficiency virus type 1 (HIV-1) Infection can vary considerably at the individual or population level. To elucidate the role of host factors that regulate variable responses to HIV-1 infection, Dr. Jianming Tang, Associate Professor of Medicine at the University of Alabama at Birmingham, proposes to test several hypotheses generated by earlier and ongoing studies. The research will examine critical cytokine and chemokine pathways for which promising preliminary data collectively point to their importance in the immunopathogenesis of HIV-1 infection. The primary work will rely on a historical cohort of 530 adolescents whose outcomes have already been documented through longitudinal (quarterly) measurements of viral load (virus-host equilibrium), CD8+CD38+ T-cell percentage (T-cell activation), and CD4+ T-cell counts (immunodeficiency). Highly sensitive, ELISA-based assays will be used to simultaneously quantify plasma levels of 16 cytokines and chemokines in untreated patients; products that are clearly correlated with contrasting HIV-1-relatedoutcomes will be evaluated in patients before and after effective antiretroviral therapy. In addition, genes encoding informative cytokines, chemokines, and related products (e.g., receptors) will be targeted for high density, bead array-based genotyping of single nucleotide polymorphisms (SNPs), supplemented and refined by TaqMan SNP assays and selective re-sequencing. Genetic associations with HIV-1-relatedoutcomes or systemic cytokine/chemokine expression will be tested for independent and potentially interactive effects in multivariable models. The same SNP dataset can be analyzed for genetic associations with sexually transmitted infections due to two other agents (Chlamydia trachomatis and herpes simplex virus type 2) commonly seen in the adolescent cohort. Overall, these multifaceted analyses, along with secondary (confirmatory) work based on studies of 120 adults with chronic HIV-1 infection, are expected to allow valuable training in biostatistical applications and provide a robust account of heterogeneous cytokine responses to HIV-1 infection. The most convincing and generalizable of findings from this work should pave the way for Dr. Tang to pursue targeted experimental studies and substantially strengthen a collaborative research program that focuses on infection and immunity in immunocompromised hosts. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Scientist Development Award - Research (K02)
Project #
1K02AI076123-01
Application #
7339125
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Embry, Alan C
Project Start
2007-09-01
Project End
2012-07-31
Budget Start
2007-09-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$100,764
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Hu, L; Song, W; Brill, I et al. (2012) Genetic variations and heterosexual HIV-1 infection: analysis of clustered genes encoding CC-motif chemokine ligands. Genes Immun 13:202-5
Song, Wei; Li, Yufeng; Wilson, Craig M et al. (2011) Identification of three immunologic correlates for HIV type 1 pathogenesis in youth. AIDS Res Hum Retroviruses 27:639-46
Song, Wei; He, Dongning; Brill, Ilene et al. (2011) Disparate associations of HLA class I markers with HIV-1 acquisition and control of viremia in an African population. PLoS One 6:e23469
Tang, Jianming; Cormier, Emmanuel; Gilmour, Jill et al. (2011) Human leukocyte antigen variants B*44 and B*57 are consistently favorable during two distinct phases of primary HIV-1 infection in sub-Saharan Africans with several viral subtypes. J Virol 85:8894-902
Williams, LaTonya D; Bansal, Anju; Sabbaj, Steffanie et al. (2011) Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers. J Virol 85:2316-24
Shrestha, Sadeep; Wiener, Howard W; Aissani, Brahim et al. (2010) Interleukin-10 (IL-10) pathway: genetic variants and outcomes of HIV-1 infection in African American adolescents. PLoS One 5:e13384
Tang, Jianming; Malhotra, Rakhi; Song, Wei et al. (2010) Human leukocyte antigens and HIV type 1 viral load in early and chronic infection: predominance of evolving relationships. PLoS One 5:e9629
Song, Wei; Ruder, Avima M; Hu, Liangyuan et al. (2009) Genetic epidemiology of glioblastoma multiforme: confirmatory and new findings from analyses of human leukocyte antigen alleles and motifs. PLoS One 4:e7157
Li, Yufeng; Ni, Rong; Song, Wei et al. (2009) Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth. Hum Genet 126:685-96
Tang, Jianming; Shao, Wenshuo; Yoo, Yun Joo et al. (2008) Human leukocyte antigen class I genotypes in relation to heterosexual HIV type 1 transmission within discordant couples. J Immunol 181:2626-35