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Proteomic studies reveal coordinated changes in T-cell expression patterns upon infection with human immunodeficiency virus type 1.

ABSTRACT: We performed an extensive two-dimensional differential in-gel electrophoresis proteomic analysis of the cellular changes in human T cells upon human immunodeficiency virus type 1 (HIV-1) infection. We detected 2,000 protein spots, 15% of which were differentially expressed at peak infection. A total of 93 proteins that changed in relative abundance were identified. Of these, 27 were found to be significantly downregulated and 66 were upregulated at peak HIV infection. Early in infection, only a small group of proteins was changed. A clear and consistent program of metabolic rerouting could be seen, in which glycolysis was downregulated and mitochondrial oxidation enhanced. Proteins that participate in apoptotic signaling were also significantly influenced. Apart from these changes, the virus also strongly influenced levels of proteins involved in intracellular transport. These and other results are discussed in light of previous microarray and proteomic studies regarding the impact of HIV-1 infection on cellular mRNA and protein content.

SUBMITTER: Ringrose JH

PROVIDER: S-EPMC2293043 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Proteomic studies reveal coordinated changes in T-cell expression patterns upon infection with human immunodeficiency virus type 1.

Ringrose Jeffrey H JH Jeeninga Rienk E RE Berkhout Ben B Speijer Dave D

Journal of virology 20080220 9

We performed an extensive two-dimensional differential in-gel electrophoresis proteomic analysis of the cellular changes in human T cells upon human immunodeficiency virus type 1 (HIV-1) infection. We detected 2,000 protein spots, 15% of which were differentially expressed at peak infection. A total of 93 proteins that changed in relative abundance were identified. Of these, 27 were found to be significantly downregulated and 66 were upregulated at peak HIV infection. Early in infection, only a ...[more]

PMID: 18287243

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Project description:We have used a V3-specific heteroduplex tracking assay (V3-HTA) with probes from two different human immunodeficiency virus type 1 (HIV-1) subtypes to examine the extent and pace of HIV-1 evolution late in infection. Twenty-four subjects with advanced HIV-1 infection (CD4(+) T-cell count, <100/microl) and stable viral loads were studied using blood plasma samples collected over a study period of approximately 9 months, during which time most of the subjects were treated with reverse transcriptase inhibitors. The V3-HTA patterns from the first and last time points were evaluated initially to determine the amounts of change in V3 sequence populations, which were primarily changes in abundance in preexisting sequence populations. Three of the 24 subjects had major changes (greater than 50% total change in the relative abundance of the sequence populations), 11 subjects had intermediate changes (10 to 50% total change), and 10 subjects had minimal changes (less than 10% total change). The average total amount of change was between two- and threefold greater in subjects with X4-like variants, although there was no correlation between average viral load and the presence of X4-like variants. V3-HTA patterns in monthly samples from 11 of the subjects were also compared. In two subjects, the amount of change exceeded 40% in a 1-month period. Overall, the pace of change in V3 populations varied between subjects and was not constant within a subject over time. Sequence analysis of the V3 variants showed that R5-like variants (not containing any X4-associated substitutions) continued to be maintained in three subjects in the presence of X4-like variants, indicating that X4 variants do not always outgrow R5 variants. The coreceptor usage of the V3 sequences from two subjects was determined using a cell fusion assay. One subject had an X4 variant that was maintained at a low level for at least 9 months, during which time the predominant variants were R5X4 (dualtropic), while in the second subject the reverse situation was observed. One of the dualtropic variants had a novel sequence motif in V3, suggesting another evolutionary pathway to altered tropism. These studies begin to probe the complexities and pace of V3 evolution in vivo, revealing dynamic patterns of change among multiple V3 sequence variants in a subset of subjects.

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Proteomic studies reveal coordinated changes in T-cell expression patterns upon infection with human immunodeficiency virus type 1.

Publications

Proteomic studies reveal coordinated changes in T-cell expression patterns upon infection with human immunodeficiency virus type 1.

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