HIV envelope induces virus expression from resting CD4+ T cells isolated from HIV-infected individuals in the absence of markers of cellular activation or apoptosis.
Resting CD4(+) T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4(+) T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4(+) T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir.
Kinter
Audrey L
AL
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. akinter@niaid.nih.edu
Umscheid
Craig A
CA
Arthos
James
J
Cicala
Claudia
C
Lin
Yin
Y
Jackson
Robert
R
Donoghue
Eileen
E
Ehler
Linda
L
Adelsberger
Joseph
J
Rabin
Ronald L
RL
Fauci
Anthony S
AS
D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002469:Cell Separation; D002478:Cells, Cultured; D015686:Gene Products, env / Q000235:genetics / Q000502:physiology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007399:Interphase / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014775:Virus Activation / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D015415:Biomarkers; D015686:Gene Products, env; D016655:HIV Core Protein p24; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1