scholarly journals Human immunodeficiency virus-1 infection of the human promyelocytic cell line HL-60: high frequency of low-level infection and effect of subsequent cell differentiation

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 437-445
Author(s):  
PM Cannon ◽  
DG Tenen ◽  
MB Feinberg ◽  
HS Shin ◽  
S Kim
Keyword(s):  
Human Immunodeficiency Virus ◽  
Long Terminal Repeat ◽  
Cell Line ◽  
High Frequency ◽  
Terminal Repeat ◽  
Granulocytic Differentiation ◽  
Low Level ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

As a model system to study the infection of early myeloid cells by human immunodeficiency virus-1 (HIV-1), we have infected the human promyelocytic cell line, HL-60, with a recombinant selectable HIV-1 clone. A fully infected population showed a relatively high frequency of low-level infection, with 40% of subcloned cells being negative by reverse transcriptase and p24 indirect immunofluorescence analysis and displaying only low levels of supernatant p24. The same treatment of a T-lymphoid cell line produced 100% productive infections. HIV-1 infection of HL-60 did not appear to alter the state of differentiation of the cells, as assessed by surface antigen expression, regardless of the level of viral expression. Furthermore, infected cells were able to respond normally to chemical inducers of differentiation. Induction of differentiation towards monocyte/macrophages by phorbol myristate acetate activated the HIV-1 long terminal repeat in a transient transfection system, and there was a corresponding increase in viral production from the infected subclones. Granulocytic differentiation, as stimulated by dimethyl sulfoxide or retinoic acid, had no effect on long terminal repeat activity and did not stimulate viral replication. These data suggest that low-level HIV-1 infections may be established at a relatively high frequency in myeloid precursor cells, and that different pathways of promyelocytic differentiation vary in their ability to stimulate HIV-1 replication.

scholarly journals Human immunodeficiency virus-1 infection of the human promyelocytic cell line HL-60: high frequency of low-level infection and effect of subsequent cell differentiation

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 437-445 ◽  
Author(s):  
PM Cannon ◽  
DG Tenen ◽  
MB Feinberg ◽  
HS Shin ◽  
S Kim
Keyword(s):  
Human Immunodeficiency Virus ◽  
Long Terminal Repeat ◽  
Cell Line ◽  
High Frequency ◽  
Terminal Repeat ◽  
Granulocytic Differentiation ◽  
Low Level ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Abstract As a model system to study the infection of early myeloid cells by human immunodeficiency virus-1 (HIV-1), we have infected the human promyelocytic cell line, HL-60, with a recombinant selectable HIV-1 clone. A fully infected population showed a relatively high frequency of low-level infection, with 40% of subcloned cells being negative by reverse transcriptase and p24 indirect immunofluorescence analysis and displaying only low levels of supernatant p24. The same treatment of a T-lymphoid cell line produced 100% productive infections. HIV-1 infection of HL-60 did not appear to alter the state of differentiation of the cells, as assessed by surface antigen expression, regardless of the level of viral expression. Furthermore, infected cells were able to respond normally to chemical inducers of differentiation. Induction of differentiation towards monocyte/macrophages by phorbol myristate acetate activated the HIV-1 long terminal repeat in a transient transfection system, and there was a corresponding increase in viral production from the infected subclones. Granulocytic differentiation, as stimulated by dimethyl sulfoxide or retinoic acid, had no effect on long terminal repeat activity and did not stimulate viral replication. These data suggest that low-level HIV-1 infections may be established at a relatively high frequency in myeloid precursor cells, and that different pathways of promyelocytic differentiation vary in their ability to stimulate HIV-1 replication.

scholarly journals Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3'-long terminal repeat transgene.

1994 ◽  
Vol 179 (3) ◽  
pp. 797-807 ◽  
Author(s):  
D Lindemann ◽  
R Wilhelm ◽  
P Renard ◽  
A Althage ◽  
R Zinkernagel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Long Terminal Repeat ◽  
Terminal Repeat ◽  
Mouse Strains ◽  
Enhancer Element ◽  
Immunodeficiency Virus ◽  
Severe Immunodeficiency ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

We have generated several transgenic mouse strains carrying a human immunodeficiency virus 1 (HIV-1) NEF/3' long terminal repeat (LTR) transgene under control of a T cell-specific promoter-enhancer element, showing a depletion of CD4+ T cells in the thymus and periphery. The immunological functions of the line with the most dramatic changes in lymphocyte populations, B6/338L, were analyzed in greater detail. The presence of the transgene in the heterozygous animal is associated with a dominant severe immunodeficiency. Older animals develop lymph-adenopathy and splenomegaly. CD4+CD8+ and CD4+CD8- single positive thymocytes already are depleted in these mice at the earliest stages in ontogeny, and peripheral T cells are reduced in frequency and present cell surface marker expression, which is characteristic for memory and activated T cells. The immunological response of B6/338L mice to several viral infections is also greatly impaired. Thus, the HIV-1 NEF/3' LTR as transgene in T cells can cause immunodeficiency and disease with striking similarities to a known retrovirus-induced immunodeficiency called murine AIDS (H. C. Morse III, S. K. Chattopadhyay, M. Makino, T. N. Frederickson, A. W. Hügin, and J. W. Hartley. 1992. AIDS. 6:607).

scholarly journals Latency-Associated Nuclear Antigen Encoded by Kaposi's Sarcoma-Associated Herpesvirus Interacts with Tat and Activates the Long Terminal Repeat of Human Immunodeficiency Virus Type 1 in Human Cells

2001 ◽  
Vol 75 (18) ◽  
pp. 8761-8771 ◽  
Author(s):  
Teresa S. Hyun ◽  
Chitra Subramanian ◽  
Murray A. Cotter ◽  
Robert A. Thomas ◽  
Erle S. Robertson
Keyword(s):  
Human Immunodeficiency Virus ◽  
Long Terminal Repeat ◽  
Cell Line ◽  
Transient Transfection ◽  
Terminal Repeat ◽  
Nuclear Antigen ◽  
The Core ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The latency-associated nuclear antigen (LANA) is constitutively expressed in cells infected with the Kaposi's sarcoma (KS) herpesvirus (KSHV), also referred to as human herpesvirus 8. KSHV is tightly associated with body cavity-based lymphomas (BCBLs) in immunocompromised patients infected with human immunodeficiency virus (HIV). LANA, encoded by open reading frame 73 of KSHV, is one of a small subset of proteins expressed during latent infection and was shown to be important in tethering the viral episome to host chromosomes. Additionally, it has been shown that LANA can function as a regulator of transcription. However, its role in the progression of disease is still being elucidated. Since KS is one of the most common AIDS-associated cancers in the United States and BCBLs appear predominantly in AIDS patients, we examined whether LANA is able to regulate the HIV type 1 (HIV-1) long terminal repeat (LTR). Using luciferase-based transient transfection assays, we found that LANA was able to transactivate the HIV-1 LTR in the human B-cell line BJAB, human monocytic cell line U937, and the human embryonic kidney fibroblast cell line 293T. Moreover, we observed that the virus-encoded HIV transactivator protein Tat cooperated with LANA in activation of the LTR in a dose-response fashion with increasing amounts of LANA. Surprisingly, LANA alone was sufficient to transactivate the HIV-1 LTR in BJAB cells. In similar assays using a HIV-1 LTR construct with the core enhancer elements deleted; the activity of LANA was diminished but not abolished, indicating a mechanism which involves the cooperation of the core enhancer elements and downstream elements which include Tat. Furthermore, transient transfection of an infectious clone of HIV with LANA demonstrated effects similar to those seen in the reporter assays based on Western blot analysis of HIV Gag polypeptide p24. Interestingly, we also demonstrated that the carboxy terminus of LANA associates with Tat in cells and in vitro. These experiments suggest a role for LANA in activating the HIV-1 LTR through association with cellular molecules targeting the core enhancer elements and Tat and may have important consequences in increasing the levels of HIV in infected individuals and, hence, the disease state.

Activation of the Human Immunodeficiency Virus-1 Long Terminal Repeat by Respiratory Burst Oxidants of Neutrophils

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 350-356
Author(s):  
Seymour J. Klebanoff ◽  
Catherine M. Headley
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Long Terminal Repeat ◽  
Respiratory Burst ◽  
Terminal Repeat ◽  
Luciferase Reporter ◽  
Human Neutrophils ◽  
Jurkat T Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) introduced in association with the luciferase reporter gene into Jurkat T cells was strongly activated by a combination of human neutrophils and phorbol myristate acetate (PMA). Activation was not observed when normal neutrophils were replaced by neutrophils which lack a respiratory burst, ie, from a patient with chronic granulomatous disease (CGD), was strongly inhibited by catalase, was potentiated by vanadate, was stimulated by relatively low concentrations of azide, and was inhibited by selective inhibitors of protein kinase C (PKC). The PMA affected activation in three ways: (1) by directly activating the LTR in Jurkat LTRluc; (2) by inducing a respiratory burst in neutrophils with the formation of H2O2; and (3) by increasing the sensitivity of Jurkat LTRluc to the activating effect of H2O2. When PMA was replaced by opsonized zymosan as the neutrophil stimulus, activation of the LTR was low unless azide was added. Activation in the presence of azide was not seen when CGD neutrophils were used or when catalase was added, suggesting that azide acts by inhibiting the degradation of H2O2. These findings indicate that activation of the HIV-1 LTR in Jurkat T cells can be induced by H2O2 released by neutrophils, particularly when PKC is concomitantly activated.

scholarly journals Effect of tamoxifen on regulation of viral replication and human immunodeficiency virus (HIV) long terminal repeat-directed transcription in cells chronically infected with HIV-1

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 696-703 ◽  
Author(s):  
J Laurence ◽  
H Cooke ◽  
SK Sikder
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Long Terminal Repeat ◽  
Terminal Repeat ◽  
Consensus Sequences ◽  
Kinase C ◽  
Immunodeficiency Virus ◽  
Cellular Dna ◽  
Hiv 1 ◽  
In Cells

The protein kinase C (PKC) activator phorbol myristate acetate (PMA) was used to upregulate viral replication in a clone of promonocytic cells chronically infected with human immunodeficiency virus (HIV)-1. Induction of virus could be inhibited by the triphenylethylene anti- estrogen tamoxifen at concentrations that had minimal effects on cellular DNA synthetic responses and cell cycle kinetics. This effect correlated with tamoxifen's ability to block PMA-mediated enhancement of HIV-promoter-driven transactivation in cells of monocyte and CD4+ T- lymphocyte lineages. No interference with a primary infection was noted. Tamoxifen's mechanism of action may relate both to its capacity to inhibit PKC and to consensus sequences for gonadal steroid responsive elements in the HIV long terminal repeat, as it was able to partially inhibit another HIV activator, 5-azacytidine, which does not modulate PKC function. The finding that regulation of HIV in a model for low-level chronic or latent infection is amenable to a nonimmunosuppressive steroid antagonist may suggest approaches to pharmacologic intervention early in HIV infection.

scholarly journals Effect of tamoxifen on regulation of viral replication and human immunodeficiency virus (HIV) long terminal repeat-directed transcription in cells chronically infected with HIV-1

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 696-703 ◽  
Author(s):  
J Laurence ◽  
H Cooke ◽  
SK Sikder
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Long Terminal Repeat ◽  
Terminal Repeat ◽  
Consensus Sequences ◽  
Kinase C ◽  
Immunodeficiency Virus ◽  
Cellular Dna ◽  
Hiv 1 ◽  
In Cells

Abstract The protein kinase C (PKC) activator phorbol myristate acetate (PMA) was used to upregulate viral replication in a clone of promonocytic cells chronically infected with human immunodeficiency virus (HIV)-1. Induction of virus could be inhibited by the triphenylethylene anti- estrogen tamoxifen at concentrations that had minimal effects on cellular DNA synthetic responses and cell cycle kinetics. This effect correlated with tamoxifen's ability to block PMA-mediated enhancement of HIV-promoter-driven transactivation in cells of monocyte and CD4+ T- lymphocyte lineages. No interference with a primary infection was noted. Tamoxifen's mechanism of action may relate both to its capacity to inhibit PKC and to consensus sequences for gonadal steroid responsive elements in the HIV long terminal repeat, as it was able to partially inhibit another HIV activator, 5-azacytidine, which does not modulate PKC function. The finding that regulation of HIV in a model for low-level chronic or latent infection is amenable to a nonimmunosuppressive steroid antagonist may suggest approaches to pharmacologic intervention early in HIV infection.

scholarly journals The Human Factors YY1 and LSF Repress the Human Immunodeficiency Virus Type 1 Long Terminal Repeat via Recruitment of Histone Deacetylase 1

2000 ◽  
Vol 74 (15) ◽  
pp. 6790-6799 ◽  
Author(s):  
Jason J. Coull ◽  
Fabio Romerio ◽  
Jian-Min Sun ◽  
Janet L. Volker ◽  
Katherine M. Galvin ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Long Terminal Repeat ◽  
Histone Deacetylase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Zinc Fingers ◽  
Terminal Repeat ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Enigmatic mechanisms restore the resting state in activated lymphocytes following human immunodeficiency virus type 1 (HIV-1) infection, rarely allowing persistent nonproductive infection. We detail a mechanism whereby cellular factors could establish virological latency. The transcription factors YY1 and LSF cooperate in repression of transcription from the HIV-1 long terminal repeat (LTR). LSF recruits YY1 to the LTR via the zinc fingers of YY1. The first two zinc fingers were observed to be sufficient for this interaction in vitro. A mutant of LSF incapable of binding DNA blocked repression. Like other transcriptional repressors, YY1 can function via recruitment of histone deacetylase (HDAC). We find that HDAC1 copurifies with the LTR-binding YY1-LSF repressor complex, the domain of YY1 that interacts with HDAC1 is required to repress the HIV-1 promoter, expression of HDAC1 augments repression of the LTR by YY1, and the deacetylase inhibitor trichostatin A blocks repression mediated by YY1. This novel link between HDAC recruitment and inhibition of HIV-1 expression by YY1 and LSF, in the natural context of a viral promoter integrated into chromosomal DNA, is the first demonstration of a molecular mechanism of repression of HIV-1. YY1 and LSF may establish transcriptional and virological latency of HIV, a state that has recently been recognized in vivo and has significant implications for the long-term treatment of AIDS.

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