title: Quantitative analysis of human immunodeficiency virus type 1-infected CD4+ cell proteome: dysregulated cell cycle progression and nuclear transport coincide with robust virus production.
abstract: Relatively little is known at the functional genomic level about the global host response to human immunodeficiency virus type 1 (HIV-1) infection. Microarray analyses by several laboratories, including our own, have revealed that HIV-1 infection causes significant changes in host mRNA abundance and regulation of several cellular biological pathways. However, it remains unclear what consequences these changes bring about at the protein level. Here we report the expression levels of approximately 3,200 proteins in the CD4(+) CEMx174 cell line after infection with the LAI strain of human immunodeficiency virus type 1 (HIV-1); the proteins were assessed using liquid chromatography-mass spectrometry coupled with stable isotope labeling and the accurate mass and time tag approach. Furthermore, we found that 687 (21%) proteins changed in abundance at the peak of virus production at 36 h postinfection. Pathway analysis revealed that the differential expression of proteins was concentrated in select biological pathways, exemplified by ubiquitin-conjugating enzymes in ubiquitination, carrier proteins in nucleocytoplasmic transport, cyclin-dependent kinase in cell cycle progression, and pyruvate dehydrogenase of the citrate cycle pathways. Moreover, we observed changes in the abundance of proteins with known interactions with HIV-1 viral proteins. Our proteomic analysis captured changes in the host protein milieu at the time of robust virus production, depicting changes in cellular processes that may contribute to virus replication. Continuing analyses are expected to focus on blocking virus replication by targeting these pathways and their effector proteins.
authors.affiliation: Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195-8070, USA.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Chan
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qian
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Diamond
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Marina A
authors.initials: MA
authors.lastname: Gritsenko
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Monroe
authors.forename: David G
authors.initials: DG
authors.lastname: Camp
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D021381:Protein Transport; D020543:Proteome; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D020543:Proteome; D014764:Viral Proteins