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PMID: 17494070 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Quantitative analysis of human immunodeficiency virus type 1-infected CD4+ cell proteome: dysregulated cell cycle progression and nuclear transport coincide with robust virus production.

Journal of virology ·Vol. 81 ·No. 14 ·2007-07-00 ·Pages 7571-83

Chan EY, Qian WJ, Diamond DL, Liu T, Gritsenko MA, Monroe ME, Camp DG, Smith RD, Katze MG

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.

MeSH Terms
Apoptosis Blotting, Western CD4-Positive T-Lymphocytes/metabolism Cell Cycle Cell Line DNA, Viral/genetics HIV-1/metabolism Humans Mass Spectrometry Protein Transport Proteome Spectroscopy, Fourier Transform Infrared Tandem Mass Spectrometry Viral Proteins/metabolism
Chemicals
DNA, Viral Proteome Viral Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chan Eric Y
Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195-8070, USA.
Qian Wei-Jun
Diamond Deborah L
Liu Tao
Gritsenko Marina A
Monroe Matthew E
Camp David G
Smith Richard D
Katze Michael G
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.00288-07
Published
2007-07-00
Epub
2007-00-09
Pages
7571-83
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1933372
Subset
IM
Grants
NCRR NIH HHS · P41 RR018522 · United States
NCI NIH HHS · T32 CA009229 · United States
NCRR NIH HHS · P41 RR018522-05 · United States
NCRR NIH HHS · P51 RR000166 · United States
NIDA NIH HHS · 1P30DA01562501 · United States
NCRR NIH HHS · RR00166 · United States
NCRR NIH HHS · RR018522 · United States
NCI NIH HHS · T32 CA09229 · United States
External Links
PubMed source DOI: 10.1128/JVI.00288-07 PMC Full Text View journal details
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