Population-based variability in protein expression patterns, especially in humans, is often observed but poorly understood. Moreover, very little is known about how interindividual genetic variation contributes to protein expression patterns. To begin to address this, we describe elements of technical and biological variations contributing to expression of 544 proteins in a population of 24 individual human lymphoblastoid cell lines that have been extensively genotyped as part of the International HapMap Project. We determined that expression levels of 10% of the proteins were tightly correlated to cell doubling rates. Using the publicly available genotypes for these lymphoblastoid cell lines, we applied a genetic association approach to identify quantitative trait loci associated with protein expression variation. Results identified 24 protein forms corresponding to 15 proteins for which genetic elements were responsible for >50% of the expression variation. The genetic variation associated with protein expression levels were located in cis with the gene coding for the transcript of the protein for 19 of these protein forms. Four of the genetic elements identified were coding non-synonymous single nucleotide polymorphisms that resulted in migration pattern changes in the two-dimensional gel. This is the first description of large scale proteomics analysis demonstrating the direct relationship between genome and proteome variations in human cells. Molecular & Cellular Proteomics 9: 1383-1399, 2010.

Viruses frequently infect the heart but clinical myocarditis is rare, suggesting that the cardiac antiviral response is uniquely effective. Indeed, the Type I interferon (IFN) response is cardiac cell typespecific and provides one integrated network of protection for the heart. Here, a proteomic approach was used to identify additional proteins that may be involved in the cardiac antiviral response. Reovirus-induced murine myocarditis reflects direct viral damage to cardiac cells, and offers an excellent system for study. Primary cultures of murine cardiac myocytes were infected with myocarditic or non-myocarditic reovirus strains, and whole cell lysates were compared by twodimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption / ionization -time-of-flight (MALDI-TOF/TOF) tandem mass spectrometry. Results were quantitative and reproducible, and demonstrated that whole proteome changes clustered according to viral pathogenic phenotype. Moreover, the data suggest that the heat shock protein Hsp25 is modulated differentially by myocarditic and non-myocarditic reoviruses and may play a role in the cardiac antiviral response. Members of seven virus families modulate Hsp25 or Hsp27 expression in a variety of cell types, suggesting that Hsp25 participation in the antiviral response may be widespread. However, results here provide the first evidence for a virus-induced decrease in Hsp25/27, and suggest that viruses may have evolved a mechanism to subvert this protective response, as they have for IFN.