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HIV Infection Modulates Cellular
Proteins Associated With Cardiovascular Disorders
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Reported by Jules Levin
5th IAS Capetown July 19-22 2009
Rasheed, S., Hussain, A., Yan, J. and A. Lau
Laboratory of Viral Oncology, AIDS and Proteomics Research,
Department of Pathology, Keck School of Medicine,
University of Southern California, Los Angeles, CA 90032
Corresponding Author: srasheed@usc.edu
ABSTRACT
Background: The spectrum of cardiovascular complications in HIV-infected individuals is escalating despite the reduction of virus-load by various treatments. Although dyslipidemia and related disorders have been linked to antiretroviral drug effects, molecular mechanisms or disease-specific biomarkers remain unidentified. Moreover, it is impossible to distinguish proteins that are dysregulated due to HIV-infection or antiviral drugs since multiple genetic, epigenetic, dietary and pharmaceutical factors are operative in vivo. We have therefore studied changes in cellular proteins in response to HIV-infection or the drug.
Methods: Subtractive proteomics technology was used to compare genome-wide proteins from HIV-infected and uninfected T-cells before and after treatment with antiviral drug Zidovudine in vitro. All dysregulated proteins were evaluated at various stages of virus replication and cell growth over a period of >2 years. Each protein was confirmed in multiple gels by mass spectrometry
Results: Functional bioinformatics and protein-interaction pathway analyses have identified 30 de novo synthesized or differentially regulated proteins post -HIV infection. Disease-specific analyses indicated that each protein is significantly associated with enhanced atherosclerosis plaque formation (n=14), ischemia (n=8), aortic aneurysm (n=4) and vascular restenosis (n=4), (p=0.02 to0.005).
Conclusions: Chronic HIV-infection augments concomitant expression of novel receptors, enzymes and kinases that are involved in the development of cardiovascular diseases (p= 8x10-11). Since HIV replication also enhances production of low density lipoproteins and many key proteins that disrupt lipid metabolism (Rasheed et al 2008, PLoS ONE 3(8): e3003), we conclude that disease-specific pathways have already been triggered by chronic HIV-replication. The risk of developing cardiovascular complications in HIV-infected individuals is then exacerbated by various therapies. Translational studies using the new targets would lead to a better understanding of clinically significant markers that could then be used for early diagnosis of these disorders. This is the first direct evidence that novel biomarkers of coronary heart diseases are modulated directly by HIV-infection.
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