Tat protein induces self-perpetuating permissivity for productive HIV-1 infection.
We report that human immunodeficiency virus type 1 (HIV-1) has evolved a self-perpetuating mechanism to actively generate cells permissive for productive and cytopathic infection. Only activated T cells can be productively infected, which leads to their rapid depletion (2 x 10(9)/day in an infected individual). Establishment of productive HIV-1 infection therefore requires continual activations from the large pool of quiescent T cells. Tat protein, which is secreted by infected cells, activated uninfected quiescent T cells in vitro and in vivo. These Tat-activated uninfected cells became highly permissive for productive HIV-1 infection. Activation of primary T cells by Tat protein involved integrin receptors and was associated with activation of mitogen-activated protein kinases, including ERK1 and JNK kinase. Accordingly, these primary T cells progressed from G0 to the late G1 phase of the cell cycle.
Li
C J
CJ
Division of Cell Growth and Regulation, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. cjli-mbcrr.harvard.edu
Ueda
Y
Y
Shi
B
B
Borodyansky
L
L
Huang
L
L
Li
Y Z
YZ
Pardee
A B
AB
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D015696:Gene Products, tat / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D002352:Carrier Proteins; D015696:Gene Products, tat; D016023:Integrins; D054322:tat Gene Products, Human Immunodeficiency Virus; D017871:Calcium-Calmodulin-Dependent Protein Kinases