scholarly journals Short Communication: Methamphetamine Treatment Increases in Vitro and in Vivo HIV Replication

2009 ◽  
Vol 25 (11) ◽  
pp. 1117-1121 ◽  
Author(s):  
Sima Shelly Toussi ◽  
Aviva Joseph ◽  
Jian Hua Zheng ◽  
Monica Dutta ◽  
Laura Santambrogio ◽  
...  
Keyword(s):  
Short Communication ◽  
Hiv Replication

scholarly journals Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 161-167 ◽  
Author(s):  
Nicholas T. Funderburg ◽  
Elizabeth Mayne ◽  
Scott F. Sieg ◽  
Robert Asaad ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Tissue Factor ◽  
Immune Activation ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Thrombus Formation ◽  
Hiv Replication ◽  
Increased Risk

Abstract HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV+ patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.

scholarly journals Soybean-derived Bowman-Birk Inhibitor (BBI) Inhibits HIV Replication in Macrophages

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Tong-Cui Ma ◽  
Run-Hong Zhou ◽  
Xu Wang ◽  
Jie-Liang Li ◽  
Ming Sang ◽  
...  
Keyword(s):  
Cost Effective ◽  
Peripheral Blood Monocyte ◽  
Type I ◽  
Restriction Factors ◽  
Oligoadenylate Synthetase ◽  
Hiv Replication ◽  
Inhibitory Protein ◽  
Anti Hiv

Abstract The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-β and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2′,5′-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56. BBI treatment of macrophages also increased the expression of several known HIV restriction factors, including APOBEC3F, APOBEC3G and tetherin. Furthermore, BBI enhanced the phosphorylation of IRF3, a key regulator of IFN-β. The inhibition of IFN-β pathway by the neutralization antibody to type I IFN receptor (Anti-IFNAR) abolished BBI-mediated induction of the anti-HIV factors and inhibition of HIV in macrophages. These findings that BBI could activate IFN-β-mediated signaling pathway, initialize the intracellular innate immunity in macrophages and potently inhibit HIV at multiple steps of viral replication cycle indicate the necessity to further investigate BBI as an alternative and cost-effective anti-HIV natural product.

scholarly journals Ingenol Derivatives are Highly Potent and Selective Inhibitors of HIV Replication in Vitro

1996 ◽  
Vol 7 (5) ◽  
pp. 230-236 ◽  
Author(s):  
M. Fujiwara ◽  
K. Ijichi ◽  
K. Tokuhisa ◽  
K. Katsuura ◽  
G.-Y.-S. Wang ◽  
...  
Keyword(s):  
Syncytium Formation ◽  
Selective Inhibitor ◽  
Host Cells ◽  
Hiv Replication ◽  
Virus Adsorption ◽  
Mechanism Of Inhibition ◽  
Anti Hiv Agents ◽  
Anti Hiv

Ingenol 3,5,20-triacetate has recently been identified as a highly potent and selective inhibitor of HIV replication in vitro. To evaluate the potential of ingenol derivatives as anti-HIV agents, several ingenol derivatives have been synthesized and investigated for their anti-HIV activities, structure-activity relationships, and possible mechanisms of action. Among the ingenol derivatives, 13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate (RD4-2138) proved to be a highly potent and selective inhibitor of HIV replication. Its 50% effective concentration for viral replication in MT-4 cells was 0.07-0.5 nM depending on viral strains, including HIV-2. This concentration was approximately 105-fold lower than its cytotoxic threshold. RD4-2138 was also inhibitory to the syncytium formation induced by cocultivation of Molt-4 cells with Molt-4/IIIB cells (Molt-4 cells chronically infected with HIV-1). Some correlation was observed with the ingenol derivatives between their inhibitory effects on HTLV-IIIB replication and surface CD4 expression in MT-4 cells, suggesting that the mechanism of inhibition is in part attributed to the inhibition of virus adsorption through down-regulation of CD4 molecules in the host cells. However, such correlation was not identified between the inhibition of HTLV-IIIB and the activation of protein kinase C. Thus, they might have a potential as effective anti-HIV agents when toxicity in vivo could be elucidated.

scholarly journals Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo

2005 ◽  
Vol 56 (2) ◽  
pp. 372-379 ◽  
Author(s):  
Chuan-Chen Ho ◽  
Shih-Shen Lin ◽  
Ming-Yung Chou ◽  
Fang-Lung Chen ◽  
Chao-Chin Hu ◽  
...  
Keyword(s):  
Hiv Replication

scholarly journals Natural scrub typhus antibody suppresses HIV CXCR4(X4) viruses

2013 ◽  
Vol 5 (1) ◽  
pp. 8 ◽  
Author(s):  
George Watt ◽  
Pacharee Kantipong ◽  
Thierry Burnouf ◽  
Cecilia Shikuma ◽  
Sean Philpott
Keyword(s):  
Scrub Typhus ◽  
Inhibitory Effect ◽  
Cross Reactivity ◽  
Viral Population ◽  
Hiv Replication ◽  
Fusion Inhibitors ◽  
Hiv Gp120 ◽  
Hiv 1

Viral load generally rises in HIV-infected individuals with a concomitant infection, but falls markedly in some individuals with scrub typhus (ST), a common Asian rickettsial infection. ST infection appears to shift the viral population from CXCR4-using (X4) to CCR5-utilizing (R5) strains, and there is evidence of cross-reactivity between ST-specific antibodies and HIV-1. We examined the mechanism of ST suppression of HIV by measuring the effects of ST infection on X4 and R5 viruses <em>in vivo</em> and <em>in vitro</em>, and assessing the relative contributions of antibodies and chemokines to the inhibitory effect. <em>In vivo</em>, a single scrub typhus plasma infusion markedly reduced the subpopulation of HIV-1 viruses using the X4 co-receptor in all 8 recipients, and eliminated X4 viruses 6 patients. <em>In vitro</em>, the 14 ST sera tested all inhibited the replication of an X4 but not an R5 virus. This inhibitory effect was maintained if ST sera were depleted of chemokines but was lost upon removal of antibodies. Sera from ST-infected mice recognized a target that co-localized with X4 HIV gp120 in immunofluorescent experiments. These <em>in vivo </em>and <em>in vitro </em>data suggest that acute ST infection generates cross-reactive antibodies that produce potent suppression of CXCR4- but not CCR5-using HIV-1 viruses. ST suppression of HIV replication could reveal novel mechanisms that could be exploited for vaccination strategies, as well as aid in the development of fusion inhibitors and other new therapeutic regimens. This also appears to be the first instance where one pathogen is neutralized by antibody produced in response to infection by a completely unrelated organism.

scholarly journals Human Immunodeficiency Virus Bearing a Disrupted Central DNA Flap Is Pathogenic In Vivo

2007 ◽  
Vol 81 (11) ◽  
pp. 6146-6150 ◽  
Author(s):  
Matthew D. Marsden ◽  
Jerome A. Zack
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Characteristics ◽  
Deficient Mutant ◽  
Wild Type ◽  
Hiv Replication ◽  
Immunodeficiency Virus ◽  
In Vivo Growth ◽  
Kinetics Of

ABSTRACT The central DNA flap is an important component of lentiviral vectors, but its significance in the context of wild-type human immunodeficiency virus (HIV) is currently unclear. To address this issue, we have compared the in vitro infection kinetics of NL4-3 with those of a flap-deficient mutant and evaluated the in vivo growth characteristics of these viruses by using the SCID-hu mouse model of HIV infection. Flap-deficient virus was only modestly attenuated in vitro, as assessed by single-round and spreading infection assays, and exhibited levels of replication and pathogenesis close to those of the wild-type in vivo. Hence, an intact central flap is not essential for HIV replication.

scholarly journals Synergistic Inhibition of Human Immunodeficiency Virus Type 1 in vitro by Interferon Alpha and Coumermycin A1

1992 ◽  
Vol 3 (3) ◽  
pp. 183-188 ◽  
Author(s):  
G. Tachedjian ◽  
D. Tyssen ◽  
D. Jardine ◽  
S. Locarnini ◽  
C. Birch
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Interferon Alpha ◽  
Virus Type ◽  
Human Peripheral Blood ◽  
Hiv Replication ◽  
Immunodeficiency Virus

Interferon alpha, either leukocyte derived or the recombinant form, and the DNA gyrase inhibitor coumermycin A1 both inhibited human immunodeficiency virus type 1 (HIV) replication in vitro. We have found that combinations of these two agents synergistically inhibited HIV replication in human peripheral blood leucocytes (PBL). Significant inhibition was detected when both virion-associated reverse transcriptase activity and p24 levels were used as markers of replication. Mathematical analysis of data using the procedure of Chou and Chou (1987) produced combination indices of less than 1.0 for most effect levels at several combination ratios. Synergy was also evident when the classical isobologram technique was used for data analysis. Synergistic drug interactions were observed at concentrations not associated with cytotoxicity or anti-proliferative effects, and were seen at concentrations achievable in vivo.

Extract of Prunella Vulgaris Spikes Inhibits HIV Replication at Reverse Transcription in vitro and can Be Absorbed from Intestine in vivo

2000 ◽  
Vol 11 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Seiji Kageyama ◽  
Masahiko Kurokawa ◽  
Kimiyasu Shiraki
Keyword(s):  
Oral Administration ◽  
Reverse Transcription ◽  
Dextran Sulphate ◽  
Prunella Vulgaris ◽  
Hiv Reverse Transcriptase ◽  
Hiv Replication ◽  
Anti Hiv ◽  
In Cells

It has been reported that extracts of the spike of Prunella vulgaris (PS) exhibit anti-HIV activity at the adsorption and reverse transcription stages. In this study, the actual activity of PS in cells, kinetic analysis of the inhibitory activity of PS against HIV reverse transcriptase and the feasibility of oral administration were examined. First, to clarify whether this extract shows anti-HIV activity in cells in vitro, the number of copies of proviral DNA in HIV-exposed cells was calculated. The number of copies was significantly decreased in cells cultured in the presence of PS extract, but not in the presence of dextran sulphate. The activity of PS extract in the cells was also assessed by the drug addition test, during and after HIV adsorption. PS extract and dextran sulphate suppressed HIV production to similar levels when added after HIV adsorption. However, only PS extract suppressed HIV production at the same concentration when the drugs were added during HIV adsorption. Presumably, the penetration of the PS extract into the cells was required for this activity. Secondly, fractionated PS inhibited HIV reverse transcription in a non-competitive manner. This fractionated PS kept anti-HIV activity, but inhibited HIV replication and adsorption to a lesser extent compared to dextran sulphate. Lastly, an active component(s) was detected in plasma in vivo, after injection into the intestine, which demonstrates the feasibility of oral administration dosing.

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