The Mechanical and Structural Effects of HIV Proteins on Murine Carotid Arteries

2011 ◽  
Author(s):  
Laura Hansen ◽  
Manu Platt ◽  
Roy L. Sutliff ◽  
Rudolph L. Gleason
Keyword(s):  
Cardiovascular Disease ◽  
Highly Active Antiretroviral Therapy ◽  
Intima Media Thickness ◽  
Biomechanical Properties ◽  
Cardiovascular Complications ◽  
Global Epidemic ◽  
Highly Active ◽  
Atherosclerotic Lesions ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Acquired immunodeficiency syndrome (AIDS) is considered a global epidemic with over 65 million people worldwide infected with the HIV-1 virus, the causative agent [1]. The development of highly active antiretroviral therapy (HAART) has significantly increased the life expectancy of people infected with the virus by slowing the progression to the development of AIDS. However, the treatment has also led to the emergence of early onset cardiovascular complications including myocardial infarction [2] and atherosclerotic lesions [3], as well as subclinical markers of atherosclerosis including increased carotid artery intima-media thickness [4], increased arterial stiffness [5–6], and endothelial dysfunction [6]. It appears that HAART and HIV-1-infection are independent risk factors for the development of atherosclerosis in adults [7]; however, the mechanism of disease progression remains unclear. There is a pressing need to identify mechanisms of early on-set cardiovascular disease associated with HIV-1 infection and HAART and to identify therapeutic strategies to reduce cardiovascular disease in HIV patients. The overall goal of this study is to test the hypothesis that over-expression of HIV proteins will lead to alterations in the biomechanical properties of large arteries.

Treatment With Non-Nucleoside Reverse Transcriptase Inhibitor Efavirenz Leads to Increase of Carotid Intima-Media Thickness in Mice

2013 ◽  
Author(s):  
Alexander W. Caulk ◽  
Rudolph L. Gleason
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Transcriptase Inhibitor ◽  
Media Thickness ◽  
Highly Active ◽  
Atherosclerotic Lesions ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Since the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus-1 (HIV-1) are living longer lives. However, HIV-1-positive (HIV-1+) patients are now experiencing many non-AIDS related comorbidities including myocardial infarction, atherosclerotic lesions, and other preclinical markers of atherosclerosis including increased carotid intima-media thickness (cIMT), arterial stiffness, and impaired flow-mediated dilation (FMD). Studies have implicated the virus, the treatment, or both in the progression of these co-morbidities, causing the exact mechanisms of cardiovascular disease progression to remain unclear.

scholarly journals Post-Catalytic Complexes with Emtricitabine or Stavudine and HIV-1 Reverse Transcriptase Reveal New Mechanistic Insights for Nucleotide Incorporation and Drug Resistance

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4868
Author(s):  
Nicole Bertoletti ◽  
Albert H. Chan ◽  
Raymond F. Schinazi ◽  
Karen S. Anderson
Keyword(s):  
Crystal Structure ◽  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Molecular Mechanisms ◽  
X Ray Crystallography ◽  
Highly Active ◽  
Nucleotide Incorporation ◽  
Almost All ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Human immunodeficiency virus 1 (HIV-1) infection is a global health issue since neither a cure nor a vaccine is available. However, the highly active antiretroviral therapy (HAART) has improved the life expectancy for patients with acquired immunodeficiency syndrome (AIDS). Nucleoside reverse transcriptase inhibitors (NRTIs) are in almost all HAART and target reverse transcriptase (RT), an essential enzyme for the virus. Even though NRTIs are highly effective, they have limitations caused by RT resistance. The main mechanisms of RT resistance to NRTIs are discrimination and excision. Understanding the molecular mechanisms for discrimination and excision are essential to develop more potent and selective NRTIs. Using protein X-ray crystallography, we determined the first crystal structure of RT in its post-catalytic state in complex with emtricitabine, (-)FTC or stavudine (d4T). Our structural studies provide the framework for understanding how RT discriminates between NRTIs and natural nucleotides, and for understanding the requirement of (-)FTC to undergo a conformation change for successful incorporation by RT. The crystal structure of RT in post-catalytic complex with d4T provides a “snapshot” for considering the possible mechanism of how RT develops resistance for d4T via excision. The findings reported herein will contribute to the development of next generation NRTIs.

scholarly journals Advances in Continuous Microfluidics-Based Technologies for the Study of HIV Infection

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 982 ◽  
Author(s):  
Joëlle Eid ◽  
Marylène Mougel ◽  
Marius Socol
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Wide Spectrum ◽  
Microfluidic Chips ◽  
Basic Study ◽  
Highly Active ◽  
Aids Progression ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Aids Diagnosis ◽  
Hiv 1

HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS). It affects millions of people worldwide and the pandemic persists despite the implementation of highly active antiretroviral therapy. A wide spectrum of techniques has been implemented in order to diagnose and monitor AIDS progression over the years. Besides the conventional approaches, microfluidics has provided useful methods for monitoring HIV-1 infection. In this review, we introduce continuous microfluidics as well as the fabrication and handling of microfluidic chips. We provide a review of the different applications of continuous microfluidics in AIDS diagnosis and progression and in the basic study of the HIV-1 life cycle.

scholarly journals Loss of the Perforin Cytotoxic Pathway Predisposes Mice to Experimental Cytomegalovirus Retinitis

2003 ◽  
Vol 77 (6) ◽  
pp. 3402-3408 ◽  
Author(s):  
Richard D. Dix ◽  
Eckhard R. Podack ◽  
Scott W. Cousins
Keyword(s):  
T Lymphocytes ◽  
Highly Active Antiretroviral Therapy ◽  
Retinal Disease ◽  
Murine Cytomegalovirus ◽  
Mrna Levels ◽  
Reverse Transcription Pcr ◽  
Highly Active ◽  
Series Of Experiments ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

ABSTRACT AIDS-related human cytomegalovirus (HCMV) retinitis continues to be a chronic ophthalmologic problem among human immunodeficiency virus type 1 (HIV-1)-infected patients who do not respond to highly active antiretroviral therapy. Although HCMV retinitis occurs during HIV-1-induced immunosuppression, the precise effector mechanism(s) that fails during the immunopathogenesis of AIDS to allow onset and progression of HCMV retinal disease remains unclear. We therefore performed a series of experiments to explore the relative roles of distinct pathways of lymphocyte-mediated cytotoxicity in either resistance or susceptibility to experimental murine cytomegalovirus (MCMV) retinitis in mice. Whereas mutant C57BL/6 mice deficient in the Fas/FasL cytotoxic pathway (gld mice) were identical to normal C57BL/6 mice and exhibited absolute resistance to retinal necrosis following subretinal MCMV inoculation, knockout C57BL/6 mice deficient in the perforin cytotoxic pathway (PKO mice) were susceptible to MCMV retinitis. Susceptibility of PKO mice to MCMV retinitis correlated with increased ocular MCMV titers when compared with ocular MCMV titers of gld and normal mice. Since mice with retrovirus-induced immunodeficiency syndrome (MAIDS) exhibited a frequency and severity of MCMV retinitis that were equivalent to those observed in PKO mice, we hypothesized that susceptibility to MCMV retinitis during MAIDS correlates with a decrease in the perforin cytotoxic pathway. To test this hypothesis, we developed a quantitative competitive reverse transcription-PCR assay to measure mouse perforin mRNA levels in the splenic T lymphocytes and MCMV-inoculated eyes of normal mice or mice with MAIDS. Perforin mRNA levels in splenic T lymphocytes were significantly decreased during MAIDS, by ∼100-fold, from perforin mRNA levels in normal mice. Moreover, MCMV-inoculated eyes destined to develop retinitis during MAIDS also showed a significant decrease in perforin mRNA levels from the perforin mRNA levels of MCMV-inoculated eyes of normal mice destined to be resistant to retinitis. As expected, perforin mRNA could not be detected in unmanipulated and uninfected eyes of normal mice. These results provide the first evidence that the perforin cytotoxic pathway is more important than the Fas/FasL cytotoxic pathway in providing resistance to experimental MCMV retinitis and that loss of the perforin cytotoxic pathway predisposes to MCMV retinitis.

scholarly journals Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

1999 ◽  
Vol 96 (26) ◽  
pp. 15167-15172 ◽  
Author(s):  
N. M. Ferguson ◽  
F. deWolf ◽  
A. C. Ghani ◽  
C. Fraser ◽  
C. A. Donnelly ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Highly Active ◽  
Hiv 1
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