HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication.
Certain HIV-encoded proteins modify host-cell gene expression in a manner that facilitates viral replication. These activities may contribute to low-level viral replication in nonproliferating cells. Through the use of oligonucleotide microarrays and high-throughput Western blotting we demonstrate that one of these proteins, gp120, induces the expression of cytokines, chemokines, kinases, and transcription factors associated with antigen-specific T cell activation in the absence of cellular proliferation. Examination of transcriptional changes induced by gp120 in freshly isolated peripheral blood mononuclear cells and monocyte-derived-macrophages reveals a broad and complex transcriptional program conducive to productive infection with HIV. Observations include the induction of nuclear factor of activated T cells, components of the RNA polymerase II complex including TFII D, proteins localized to the plasma membrane, including several syntaxins, and members of the Rho protein family, including Cdc 42. These observations provide evidence that envelope-mediated signaling contributes to the productive infection of HIV in suboptimally activated T cells.
Cicala
Claudia
C
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ccicala@nih.gov
Arthos
James
J
Selig
Sara M
SM
Dennis
Glynn
G
Hosack
Douglas A
DA
Van Ryk
Donald
D
Spangler
Marion L
ML
Steenbeke
Tavis D
TD
Khazanie
Prateeti
P
Gupta
Neil
N
Yang
Jun
J
Daucher
Marybeth
M
Lempicki
Richard A
RA
Fauci
Anthony S
AS
D000818:Animals; D016466:CHO Cells; D002455:Cell Division; D018925:Chemokines / Q000235:genetics; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008561:Membrane Fusion / Q000187:drug effects / Q000235:genetics; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011494:Protein Kinases / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D014157:Transcription Factors / Q000235:genetics; D014779:Virus Replication / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D015699:HIV Envelope Protein gp120; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D011494:Protein Kinases