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Title: The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

Abstract

Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with andmore » without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1039104
Report Number(s):
PNNL-SA-81597
40072; 400412000; TRN: US201209%%167
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Clinical Proteomics
Additional Journal Information:
Journal Volume: 9
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; AIDS VIRUS; CENTRAL NERVOUS SYSTEM; CEREBROSPINAL FLUID; DISEASES; IMMUNITY; INFECTIOUS DISEASES; PEPTIDES; PLASTICITY; PRECURSOR; PROTEINS; RNA; amyloid; cerebrospinal fluid; HIV; pathway; proteomics; Environmental Molecular Sciences Laboratory

Citation Formats

Angel, Thomas E, Jacobs, Jon M, Spudich, Serena S, Gritsenko, Marina A, Fuchs, Dietmar, Liegler, Teri, Zetterberg, Henrik, Camp, David G, Price, Richard W, and Smith, Richard D. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.. United States: N. p., 2012. Web. doi:10.1186/1559-0275-9-3.
Angel, Thomas E, Jacobs, Jon M, Spudich, Serena S, Gritsenko, Marina A, Fuchs, Dietmar, Liegler, Teri, Zetterberg, Henrik, Camp, David G, Price, Richard W, & Smith, Richard D. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.. United States. doi:10.1186/1559-0275-9-3.
Angel, Thomas E, Jacobs, Jon M, Spudich, Serena S, Gritsenko, Marina A, Fuchs, Dietmar, Liegler, Teri, Zetterberg, Henrik, Camp, David G, Price, Richard W, and Smith, Richard D. Tue . "The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.". United States. doi:10.1186/1559-0275-9-3.
@article{osti_1039104,
title = {The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.},
author = {Angel, Thomas E and Jacobs, Jon M and Spudich, Serena S and Gritsenko, Marina A and Fuchs, Dietmar and Liegler, Teri and Zetterberg, Henrik and Camp, David G and Price, Richard W and Smith, Richard D},
abstractNote = {Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.},
doi = {10.1186/1559-0275-9-3},
journal = {Clinical Proteomics},
number = ,
volume = 9,
place = {United States},
year = {2012},
month = {3}
}