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Plasma levels of complement factor I and C4b peptides are associated with HIV suppression. Boyue Wu, Zhengyu Ouyang, Christopher J. Lyon, Wei Zhang, Tori Clift, Christopher R. Bone, Bo-An Li, Zhen Zhao, Jason T. Kimata, Xu G. Yu, and Ye Hu ACS Infect. Dis., Just Accepted Manuscript • DOI: 10.1021/acsinfecdis.7b00042 • Publication Date (Web): 01 Sep 2017 Downloaded from http://pubs.acs.org on September 4, 2017
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ACS Infectious Diseases
Plasma levels of complement factor I and C4b peptides are associated with HIV suppression. Boyue Wu,1,2 Zhengyu Ouyang,3 Christopher J. Lyon,1,4 Wei Zhang,4,5 Tori Clift,4 Christopher R. Bone,4 Boan Li,6 Zhen Zhao,7 Jason T. Kimata,8 Xu G. Yu3, Ye Hu *1,4,9
1
Biodesign Center for Personalized Diagnostics, the Biodesign Institute, Arizona State
University, 727 E. Tyler Street, Tempe, AZ 85281, United States 2
College of Laboratory Medicine, Tianjin Medical University, 1 Guangdong Road, Tianjin
300203, China 3
Ragon Institute of MGH, MIT and Harvard University, 400 Technology Square, Boston, MA
02139-3583, United States 4
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue,
Houston, TX 77030, United States 5
Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang,
Liaoning Province, China 6
Center for Clinical Laboratory, 302th Military Hospital of China, 100 Middle Section of West
4th Ring Road, Beijing 100038, China 7
Department of Laboratory Medicine, Clinical Center, National Institutes of Health, 9000
Rockville Pike, Bethesda, MD 20892, United States 8
Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor
Plaza, Houston, TX 77030, United States 9
School of Biological and Health Systems Engineering, Virginia G. Piper, Arizona State
University, 727 E. Tyler Street, Tempe, AZ 85281, United States Corresponding Author: Ye Hu,
[email protected].
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ACS Infectious Diseases
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Abstract (150/150 words) Individuals who exhibit long-term HIV suppression and CD4 T-cell preservation without antiretroviral therapy are of great interest for HIV research. There is currently no robust method for rapid identification of these ‘HIV controller’ subjects, however, although HLA-B*57 genotype exhibits modest sensitivity for this phenotype. Complement C3b and C4b can influence HIV infection and replication, but studies have not examined their possible link to HIV controller status. We analyzed HLA-B*57 genotype and complement levels in HIV-positive patients receiving suppressive antiretroviral therapy, untreated HIV controllers and HIV-negative subjects to identify factors associated with HIV controller status. Our results revealed that the plasma levels of three C4b-derived peptides and complement factor I outperformed all other assayed biomarkers for HIV controller identification, although we could not analyze the predictive value of biomarker combinations with the current sample size. We believe this rapid screening approach may prove useful for improved identification of HIV controllers.
Keywords: human immunodeficiency virus; complement factor I; complement C4b, elite controllers;
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ACS Infectious Diseases
A small fraction of HIV-infected individuals exhibit long-term viral control and CD4 T-cell preservation in the absence of anti-retroviral therapy 1, 2. These “HIV controllers” can be divided into viremic controllers (VC; ~3.34% of HIV-positive patients), who have low but detectable viremia (usually
