scholarly journals Anti-Human Immunodeficiency Virus Activity of Tau Interferon in Human Macrophages: Involvement of Cellular Factors and β-Chemokines

2003 ◽  
Vol 77 (23) ◽  
pp. 12914-12920 ◽  
Author(s):  
Christine Rogez ◽  
Marc Martin ◽  
Nathalie Dereuddre-Bosquet ◽  
Jacques Martal ◽  
Dominique Dormont ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Monocyte ◽  
Type I ◽  
Rnase L ◽  
Oligoadenylate Synthetase ◽  
Hiv Replication ◽  
Human Macrophages ◽  
Hiv Rna ◽  
Type I Ifns ◽  
Immunodeficiency Virus

ABSTRACT Tau interferon (IFN-τ) is a noncytotoxic type I IFN responsible for maternal recognition of the fetus in ruminants. IFN-τ inhibits human immunodeficiency virus (HIV) replication more strongly than human IFN-α, particularly in human monocyte-derived macrophages. In this study performed in human macrophages, IFN-τ efficiently inhibited the early steps of the biological cycle of HIV, decreasing intracellular HIV RNA and inhibiting the initiation of the reverse transcription of viral RNA into proviral DNA. Two mechanisms induced by IFN-τ treatment in macrophages may account for this inhibition: (i) the synthesis of the cellular antiviral factors such as 2′,5′-oligoadenylate synthetase/RNase L and MxA protein and (ii) an increased production of MIP-1α, MIP-1β, and RANTES, which are natural ligands of CCR5, the principal coreceptor of HIV on macrophages. Our results suggest that IFN-τ induces the same antiviral pathways in macrophages as other type I IFNs but without associated toxicity.

scholarly journals RNase L Inhibitor Is Induced during Human Immunodeficiency Virus Type 1 Infection and Down Regulates the 2-5A/RNase L Pathway in Human T Cells

1999 ◽  
Vol 73 (1) ◽  
pp. 290-296 ◽  
Author(s):  
Camille Martinand ◽  
Céline Montavon ◽  
Tamim Salehzada ◽  
Michelle Silhol ◽  
Bernard Lebleu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Rnase L ◽  
Hiv Replication ◽  
Hiv Rna ◽  
Rnase L Inhibitor ◽  
Immunodeficiency Virus ◽  
Infected Cells

ABSTRACT The interferon-regulated 2-5A/RNase L pathway plays a major role in the antiviral and antiproliferative activities of these cytokines. Several viruses, however, have evolved strategies to escape the antiviral activity of the 2-5A/RNase L pathway. In this context, we have cloned a cDNA coding for the RNase L inhibitor (RLI), a protein that specifically inhibits RNase L and whose regulated expression in picornavirus-infected cells down regulates the activity of the 2-5A/RNase L pathway. We show here that RLI increases during the course of human immunodeficiency virus type 1 (HIV-1) infection, which may be related to the downregulation of RNase L activity that has been described to occur in HIV-infected cells. In order to establish a possible causal relationship between these observations, we have stably transfected H9 cells with RLI sense or antisense cDNA-expressing vectors. The overexpression of RLI causes a decrease in RNase L activity and a twofold enhancement of HIV production. This increase in HIV replication correlates with an increase in HIV RNA and proteins. In contrast, reduction of RLI levels in RLI antisense cDNA-expressing clones reverses the inhibition of RNase L activity associated with HIV multiplication and leads to a threefold decrease in the viral load. This anti-HIV activity correlated with a decrease in HIV RNA and proteins. These findings demonstrate that the level of RLI, via its modulation of RNase L activity, can severely impair HIV replication and suggest the involvement of RLI in the inhibition of the 2-5A/RNase L system observed during HIV infection.

scholarly journals In Vitro Cell-Mediated Immune Responses of Human Immunodeficiency Virus-Infected and -Uninfected Individuals to Whole Cytomegalovirus Antigens and Their Subunits

2008 ◽  
Vol 15 (9) ◽  
pp. 1398-1409 ◽  
Author(s):  
A. Weinberg ◽  
J. Spritzler ◽  
M. Nokta ◽  
R. Schrier ◽  
A. Landay ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Interleukin 2 ◽  
Cell Mediated Immunity ◽  
Hiv Replication ◽  
Hiv Rna ◽  
Highly Sensitive ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Cd4 Cell

ABSTRACT The aim of this study was to optimize the ability to detect cytomegalovirus (CMV)-specfic cell-mediated immunity (CMI) in human immunodeficiency virus (HIV)-infected individuals by comparing different assays (the lymphocyte proliferation assay [LPA] and assays for gamma interferon [IFN-γ] and interleukin-2 [IL-2] production) and CMV antigenic preparations. Thresholds discriminating positive from negative CMI results were developed with specimens from 36 CMV-seropositive and 21 CMV-seronegative healthy individuals. The analysis showed that the CMI elicited by any of the four CMV whole lysates tested in this study tended to be more robust and sensitive than the responses to the subunit antigens gB and pp65. LPA and inducible IFN-γ but not IL-2 were highly sensitive measures of CMV-specific CMI in HIV-infected and -uninfected individuals. The ability to detect CMV-specific LPA or IFN-γ responses in HIV-infected individuals significantly increased with higher CD4 cell numbers. Nevertheless, the proportion of HIV-infected subjects with CD4 counts of ≥500 cells/μl who had a detectable CMV-specific CMI remained significantly lower than that of healthy adults. The ability to detect CMV-specific CMI in HIV-infected individuals decreased with higher levels of HIV replication, with discriminative thresholds of 103 to 104 HIV RNA copies/ml of plasma, for LPA or inducible IFN-γ production elicited by different antigens. The LPA responses obtained with CMV whole lysate and phytohemagglutinin were significantly correlated in HIV-infected subjects but not uninfected controls, indicating a novel characteristic of the CMI defect caused by HIV. The intrasubject variabilities of the CMV-specific CMI were similar in HIV-infected and -uninfected individuals. These data show that LPA and the inducible IFN-γ production elicited by CMV whole lysates may be used to assess modifications of the immune competency of HIV-infected individuals.

Effect of a single bout of acute exercise on plasma human immunodeficiency virus RNA levels

1999 ◽  
Vol 86 (4) ◽  
pp. 1197-1201 ◽  
Author(s):  
Ronenn Roubenoff ◽  
Paul R. Skolnik ◽  
Abby Shevitz ◽  
Laura Snydman ◽  
Alicia Wang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Acute Phase Response ◽  
Acute Exercise ◽  
Creatine Phosphokinase ◽  
Hiv Replication ◽  
Viral Loads ◽  
Hiv Rna ◽  
Serum Creatine Phosphokinase ◽  
Immunodeficiency Virus ◽  
Rna Levels

Acute exercise is known to activate the immune system and thus could lead to increased human immunodeficiency virus (HIV) replication. We sought to determine whether a single acute bout of exercise, similar to what people experience when starting an intensive exercise program, has a detrimental effect on plasma HIV RNA levels. Twenty-five patients with HIV infection performed one 15-min bout of acute exercise. Absolute neutrophil counts, serum creatine phosphokinase, and 72-h urinary 3-methylhistidine (a marker of muscle protein breakdown) were measured before and after the exercise, along with plasma HIV RNA levels. There were increases in neutrophil counts ( P < 0.06), serum creatine phosphokinase ( P < 0.01), and urinary 3-methylhistidine ( P < 0.01) in response to exercise, indicating a mild acute-phase response with muscle proteolysis. However, mean HIV RNA, which was elevated at baseline in 22 of the 25 subjects (mean of 4 × 105 ± 0.7 × 105 copies/ml), did not increase during the week after exercise ( P = 0.12). Small changes in RNA were seen in the three subjects with initially undetectable HIV RNA, but the significance of these changes is unclear. Acute exercise does not have a deleterious effect on HIV replication in adults with high viral loads. Because regular exercise training has not been shown to activate the acute-phase response, the lack of increased viral loads in response to an acute exercise intervention suggests that exercise training is safe in people with HIV infection.

scholarly journals Nitric Oxide Synthesis Enhances Human Immunodeficiency Virus Replication in Primary Human Macrophages

2000 ◽  
Vol 74 (19) ◽  
pp. 8904-8912 ◽  
Author(s):  
Donatienne Blond ◽  
Hervé Raoul ◽  
Roger Le Grand ◽  
Dominique Dormont
Keyword(s):  
Nitric Oxide ◽  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Primary Cultures ◽  
Inos Mrna ◽  
No Production ◽  
Hiv Replication ◽  
Human Macrophages ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Macrophages are suspected to play a major role in human immunodeficiency virus (HIV) infection pathogenesis, not only by their contribution to virus dissemination and persistence in the host but also through the dysregulation of immune functions. The production of NO, a highly reactive free radical, is thought to act as an important component of the host immune response in several viral infections. The aim of this study was to evaluate the effects of HIV type 1 (HIV-1) Ba-L replication on inducible nitric oxide synthase (iNOS) mRNA expression in primary cultures of human monocyte-derived macrophages (MDM) and then examine the effects of NO production on the level of HIV-1 replication. Significant induction of the iNOS gene was observed in cultured MDM concomitantly with the peak of virus replication. However, this induction was not accompanied by a measurable production of NO, suggesting a weak synthesis of NO. Surprisingly, exposure to low concentrations of a NO-generating compound (sodium nitroprusside) andl-arginine, the natural substrate of iNOS, results in a significant increase in HIV replication. Accordingly, reduction ofl-arginine bioavailability after addition of arginase to the medium significantly reduced HIV replication. The specific involvement of NO was further demonstrated by a dose-dependent inhibition of viral replication that was observed in infected macrophages exposed to N G-monomethyll-arginine andN G-nitro-l-arginine methyl ester (l-NAME), two inhibitors of the iNOS. Moreover, an excess of l-arginine reversed the addition of L-NAME, confirming that an arginine-dependent mechanism is involved. Finally, inhibitory effects of hemoglobin which can trap free NO in culture supernatants and in biological fluids in vivo confirmed that endogenously produced NO could interfere with HIV replication in human macrophages.

scholarly journals Lambda Interferon Inhibits Human Immunodeficiency Virus Type 1 Infection of Macrophages

2009 ◽  
Vol 83 (8) ◽  
pp. 3834-3842 ◽  
Author(s):  
Wei Hou ◽  
Xu Wang ◽  
Li Ye ◽  
Lin Zhou ◽  
Zhan-Qiu Yang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Type I ◽  
Type I Ifns ◽  
Immunodeficiency Virus ◽  
Intracellular Expression ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT The newly identified type III interferon (IFN-λ) has antiviral activity against a broad spectrum of viruses. We thus examined whether IFN-λ has the ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection of blood monocyte-derived macrophages that expressed IFN-λ receptors. Both IFN-λ1 and IFN-λ2, when added to macrophage cultures, inhibited HIV-1 infection and replication. This IFN-λ-mediated anti-HIV-1 activity is broad, as IFN-λ could inhibit infection by both laboratory-adapted and clinical strains of HIV-1. Investigations of the mechanism(s) responsible for the IFN-λ action showed that although IFN-λ had little effect on HIV-1 entry coreceptor CCR5 expression, IFN-λ induced the expression of CC chemokines, the ligands for CCR5. In addition, IFN-λ upregulated intracellular expression of type I IFNs and APOBEC3G/3F, the newly identified anti-HIV-1 cellular factors. These data provide direct and compelling evidence that IFN-λ, through both extracellular and intracellular antiviral mechanisms, inhibits HIV-1 replication in macrophages. These findings indicate that IFN-λ may have therapeutic value in the treatment of HIV-1 infection.

scholarly journals Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages.

1987 ◽  
Vol 166 (4) ◽  
pp. 1144-1149 ◽  
Author(s):  
D D Richman ◽  
R S Kornbluth ◽  
D A Carson
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Monocyte ◽  
Human Immunodeficiency Virus Replication ◽  
Hiv Replication ◽  
New Therapeutic Approaches ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
T Lymphoblasts ◽  
Anti Hiv Agents

Primary human monocyte-derived macrophages (MDM) were shown to have diminished deoxynucleoside kinase activities compared to T lymphoblasts, and a reduced ability to phosphorylate dideoxynucleosides with anti-human immunodeficiency virus (HIV) activity. These drugs, azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyadenosine (ddA), which are potent anti-HIV agents in CD4 lymphocytes, did not inhibit HIV replication in MDM, even at concentrations of 100 microM. This drug concentration of AZT is approximately 100-fold higher than the levels attained in the serum of treated patients and the levels required to inhibit HIV replication in lymphocytes. These observations may explain the failure of AZT therapy to clear viremia, consistent with the presence of a drug-resistant reservoir of infected cells in vivo. New therapeutic approaches to inhibit the replication of HIV in MDM may be needed.

scholarly journals Partial Inhibition of Human Immunodeficiency Virus Replication by Type I Interferons: Impact of Cell-to-Cell Viral Transfer

2009 ◽  
Vol 83 (20) ◽  
pp. 10527-10537 ◽  
Author(s):  
Daniela Vendrame ◽  
Marion Sourisseau ◽  
Virginie Perrin ◽  
Olivier Schwartz ◽  
Fabrizio Mammano
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Type I Interferons ◽  
Human Immunodeficiency Virus Replication ◽  
Type I ◽  
Restriction Factors ◽  
Hiv Replication ◽  
Potent Effect ◽  
Immunodeficiency Virus ◽  
The Impact

ABSTRACT Type I interferons (IFN) inhibit several steps of the human immunodeficiency virus type 1 (HIV) replication cycle. Some HIV proteins, like Vif and Vpu, directly counteract IFN-induced restriction factors. Other mechanisms are expected to modulate the extent of IFN inhibition. Here, we studied the impact of IFN on various aspects of HIV replication in primary T lymphocytes. We confirm the potent effect of IFN on Gag p24 production in supernatants. Interestingly, IFN had a more limited effect on HIV spread, measured as the appearance of Gag-expressing cells. Primary isolates displayed similar differences in the inhibition of p24 release and virus spread. Virus emergence was the consequence of suboptimal inhibition of HIV replication and was not due to the selection of resistant variants. Cell-to-cell HIV transfer, a potent means of virus replication, was less sensitive to IFN than infection by cell-free virions. These results suggest that IFN are less active in cell cultures than initially thought. They help explain the incomplete protection by naturally secreted IFN during HIV infection and the unsatisfactory outcome of IFN treatment in HIV-infected patients.

scholarly journals Targeting RNase L to Human Immunodeficiency Virus RNA with 2-5A-Antisense

1998 ◽  
Vol 9 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Player ◽  
RK Maitra ◽  
RH Silverman ◽  
PF Torrence
Keyword(s):  
Human Immunodeficiency Virus ◽  
Solid Phase ◽  
Rnase L ◽  
Hiv Rna ◽  
Cleavage Activity ◽  
Virus Rna ◽  
Phosphoramidite Chemistry ◽  
Immunodeficiency Virus ◽  
Antisense Approach ◽  
A Cell

In an attempt to develop a lead for the application of 2–5A-antisense to the targeted destruction of human immunodeficiency virus (HIV) RNA, specific target sequences within the HIV mRNAs were identified by analysis of the theoretical secondary structure. 2-5A-antisense chimeras were chosen against a total of 11 different sequences: three in the gag mRNA, three in the rev mRNA and five in the tat mRNA. 2-5A-antisense chimera synthesis was accomplished using solid-phase phosphoramidite chemistry. These chimeras were evaluated for their activity in a cell-free assay system using purified recombinant human RNase L to effect cleavage of 32P-labelled RNA transcripts of plasmids derived from HIV NL4-3. This screening revealed that of the three 2-5A-antisense chimeras targeted against gag mRNA, only one had significant HIV RNA cleavage activity, approximately10-fold-reduced compared to the parent 2-5A tetramer and comparable to that reported for the prototypical 2-5A-anti-PKR chimera, targeted against PKR mRNA. The cleavage activity of this chimera was specific, since a scrambled antisense domain chimera and a chimera without the key 5′-monophosphate moiety were both inactive. The 10 other 2-5A-antisense chimeras against tat and rev had significantly less activity. These results imply that HIV gag RNA, like PKR RNA and a model HIV tat-oligoA- vif RNA, can be cleaved using the 2-5A-antisense approach. The results further imply that not all regions of a potential RNA target are accessible to the 2-5A-antisense approach.

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