Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though approximately 10(14) molecules are inoculated in the studies in rabbits, by day 8 or 9 ( approximately 1 week postinoculation), already all but on the order of 10(4)-10(6) molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10-20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.
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PMID:Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar, without integration, despite differing plasmid backbones or gene inserts. 1656 29

Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known homologues. In this study, we report the interaction of a SARS-CoV 7a and small glutamine-rich tetratricopeptide repeat-containing protein (SGT). SARS-CoV 7a and human SGT interaction was identified using a two-hybrid system screen and confirmed with interaction screens in cell culture and cellular co-localization studies. The SGT domain of interaction was mapped by deletion mutant analysis and results indicated that tetratricopeptide repeat 2 (aa 125-158) was essential for interaction. We also showed that 7a interacted with SARS-CoV structural proteins M (membrane) and E (envelope), which have been shown to be essential for virus-like particle formation. Taken together, our results coupled with data from studies of the interaction between SGT and HIV-1 vpu indicated that SGT could be involved in the life-cycle, possibly assembly of SARS-CoV.
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PMID:Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT. 1658 Jun 32

There are a number of antivirals as well as antiviral strategies that could be envisaged to prevent or treat severe acute respiratory syndrome (SARS) (or similar) coronavirus (CoV) infections. Targets for the prophylactic or therapeutic interventions include interaction of the spike (S) glycoprotein (S1 domain) with the host cell receptor, fusion of the S2 domain with the host cell membrane, processing of the replicase polyproteins by the virus-encoded proteases (3C-like cysteine protease [3CLpro] and papain-like cysteine protease) and other virus-encoded enzymes such as the NTPase/helicase and RNA-dependent RNA polymerase. Human monoclonal antibody blocking S1 may play an important role in the immunoprophylaxis of SARS. Fusion inhibitors reminiscent of enfuvirtide in the case of HIV may also be developed for SARS-CoV. Various peptidomimetic and nonpeptidic inhibitors of 3CLpro have been described, the best ones inhibiting SARS-CoV replication with a selectivity index greater than 1000. Human interferons, in particular alpha- and beta-interferon, as well as short interfering RNAs could further be pursued for the control of SARS. Various other compounds, often with an ill-defined mode of action but selectivity indexes up to 100, have been reported to exhibit in vitro activity against SARS-CoV: valinomycin, glycopeptide antibiotics, plant lectins, hesperetin, glycyrrhizin, aurintricarboxylic acid, chloroquine, niclosamide, nelfinavir and calpain inhibitors.
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PMID:Potential antivirals and antiviral strategies against SARS coronavirus infections. 1659 9

A comparative analysis of the 2002-2003 infectious disease outbreak, severe acute respiratory syndrome (SARS), and the HIV/AIDS epidemic that has affected the world over the past two decades reveals the significant role of socio-cultural beliefs and attitudes in the shaping of people's lifestyles and approaches to the control and prevention of epidemics. The main research question is: what can we learn from the SARS experience about effective prevention of HIV/AIDS? The sources of data include population figures on the development of these epidemics and findings from two sociological studies of representative samples of Singapore's multi-ethnic population. The comparative study illustrates the impact of cultural beliefs and attitudes in shaping the public image of these two different infectious diseases; the relevance of public image of the disease for effective prevention and control of epidemics.
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PMID:Public image and governance of epidemics: comparing HIV/AIDS and SARS. 1663 71

The triplet-based genetic code requires that translating ribosomes maintain the reading frame of a messenger RNA faithfully to ensure correct protein synthesis. However, in programmed -1 ribosomal frameshifting, a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one nucleotide backwards into an overlapping reading frame and to translate an entirely new sequence of amino acids. This process is indispensable in the replication of numerous viral pathogens, including HIV and the coronavirus associated with severe acute respiratory syndrome, and is also exploited in the expression of several cellular genes. Frameshifting is promoted by an mRNA signal composed of two essential elements: a heptanucleotide 'slippery' sequence and an adjacent mRNA secondary structure, most often an mRNA pseudoknot. How these components operate together to manipulate the ribosome is unknown. Here we describe the observation of a ribosome-mRNA pseudoknot complex that is stalled in the process of -1 frameshifting. Cryoelectron microscopic imaging of purified mammalian 80S ribosomes from rabbit reticulocytes paused at a coronavirus pseudoknot reveals an intermediate of the frameshifting process. From this it can be seen how the pseudoknot interacts with the ribosome to block the mRNA entrance channel, compromising the translocation process and leading to a spring-like deformation of the P-site transfer RNA. In addition, we identify movements of the likely eukaryotic ribosomal helicase and confirm a direct interaction between the translocase eEF2 and the P-site tRNA. Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame.
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PMID:A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting. 1668 78

The anti-RNA virus activity of polyoxometalates (POM) is reviewed, with a special emphasis on the anti-respiratory virus activities. There are many causative agents of acute viral respiratory infections; and it is rather difficult to identify the relevant agent in a given case by rapid clinical means. During acute progress of infection before the definitive diagnosis is obtained physicians need to prescribe certain broad spectrum anti-viral drugs. A titanium containing polyoxotungstate, PM-523 exhibited potent anti-influenza virus (FluV) A and anti-respiratory syncytial virus (RSV) activities in vitro. Therapeutic effect of FluV A infected mice with aerosol inhalation of PM-523 was proven. A vanadium substituted polyoxotungstate, PM-1001 has antiviral activity against FluV A, RSV, parainfluenza virus (PfluV) type 2, Dengue fiver virus, HIV-1 and SARS coronavirus in vitro. Thus, POMs have been proven to be broad spectrum and non-toxic anti-RNA virus agents in both in vitro and in vivo experiments and are promising candidates for first-line therapeutics in acute respiratory diseases.
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PMID:Anti-RNA virus activity of polyoxometalates. 1673 94

This study compares public stigma towards three types of infectious diseases- human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), severe acute respiratory syndrome (SARS), and tuberculosis (TB)-tests an attribution model of stigma, and explores the relationships between stigma and public attitudes towards government policies in Hong Kong. Using a population-based telephone survey, 3011 Hong Kong Chinese adults were randomly assigned to one of the three disease conditions and were interviewed about their attitudes and beliefs towards the assigned disease. Findings showed that public stigma was the highest towards HIV/AIDS, followed by TB and SARS. Using multi-sample model structural equation modeling, we found that the attributions of controllability, personal responsibility, and blame were applicable in explaining stigma across three disease types. Knowledge about the disease had no significant effect on stigma. Participants with less stigmatizing views had significantly more favorable attitudes towards government policies related to the diseases. The study is an important attempt in understanding the attributional mechanisms of stigma towards infectious diseases. Implications for stigma reduction and promotion of public awareness and disease prevention are discussed.
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PMID:Comparative stigma of HIV/AIDS, SARS, and tuberculosis in Hong Kong. 1676 6

All coronaviruses encode a small hydrophobic envelope (E) protein, which mediates viral assembly and morphogenesis by an unknown mechanism. We have previously shown that the E protein from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) forms cation-selective ion channels in planar lipid bilayers (Wilson, L., McKinlay, C., Gage, P., Ewart, G., 2004. SARS coronavirus E protein forms cation-selective ion channels. Virology 330(1), 322-331). We now report that three other E proteins also form cation-selective ion channels. These E proteins were from coronaviruses representative of taxonomic groups 1-3: human coronavirus 229E (HCoV-229E), mouse hepatitis virus (MHV), and infectious bronchitis virus (IBV), respectively. It appears, therefore, that coronavirus E proteins in general, belong to the virus ion channels family. Hexamethylene amiloride (HMA)--an inhibitor of the HIV-1 Vpu virus ion channel--inhibited the HCoV-229E and MHV E protein ion channel conductance in bilayers and also inhibited replication of the parent coronaviruses in cultured cells, as determined by plaque assay. Conversely, HMA had no antiviral effect on a recombinant MHV with the entire coding region of E protein deleted (MHVDeltaE). Taken together, the data provide evidence of a link between inhibition of E protein ion channel activity and the antiviral activity of HMA.
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PMID:Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication. 1681 24

The origin of acquired immune disorder syndrome (AIDS) has been the subject of substantial controversy both in the scientific community and in the popular press. The debate involves the mode of transmission of a simian virus (SIV) to humans. Both major camps in the argument presume that humans are normally free of such viruses and assume that once the simian virus was transmitted, it immediately infected some T-cells and caused the release of toxic agents that killed off bystander (uninfected) T-cells resulting in AIDS. The evolution of the Simian virus (SIV) into a human virus (HIV) is regarded as an artifact. In contrast, a fundamentally different hypothesis has been proposed [Parris GE. Med Hypotheses 2004;62(3):354-7] in which it is presumed that in hyper-endemic areas of malaria (central Africa), all primates (humans and non-human primates) have shared a retrovirus that augments their T-cell response to the malaria parasite. The virus can be called "primate T-cell retrovirus" (PTRV). Over thousands of years the virus has crossed species lines many times (with little effect) and typically adapts to the host quickly. In this model, AIDS is seen to be the result of the development of resistance of the virus (PTRV) to continuous exposure to pro-apoptotic (schizonticidal) aminoquinoline drugs used to prevent malaria. The hypothesis was originally proposed based on biochemical activities of the aminoquinolines (e.g., pamaquine (plasmoquine(TM)), primaquine and chloroquine), but recent publications demonstrated that some of these drugs definitely adversely affect HIV and other viruses and logically would cause them to evolve resistance. Review of the timeline that has been created for the evolution of HIV in humans is also shown to be qualitatively and quantitatively consistent with this hypothesis (and not with either version of the conventional hypothesis). SARS and Ebola also fit this pattern.
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PMID:AIDS: caused by development of resistance to drugs in a non-target intracellular parasite. 1709 75

Viral infections can cause many glomerular diseases. The diagnostic criteria for virus-related nephropathy include detailed clinical and laboratory data, and tissue molecular analysis. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including tropism of the virus in the kidney, induction of abnormal immune complexes, direct cytopathogenic effects, and multiorgan failure. Hepatitis B virus is associated with membranous nephropathy and mesangiocapillary glomerulonephritis in endemic areas. Hepatitis C virus causes various forms of glomerulonephritis, including cryoglobulinemia-mediated glomerulonephritis. Infection with HIV is associated with a collapsing focal segmental glomerulosclerosis, a distinctive disease that affects mainly Africans and African Americans. In the course of HIV infection, other types of immune complex glomerulonephritis can occur, most frequently in whites. Recent reports indicate a role for parvovirus B19 in 'idiopathic' collapsing focal segmental glomerulosclerosis. Both hantaviruses, and coronaviruses associated with severe acute respiratory syndrome, can lead to acute renal failure. Renal biopsy followed by appropriate serological and molecular testing is essential for defining virus-related glomerular lesions and guiding prognostic and therapeutic evaluation.
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PMID:Viral nephropathy. 1693 38


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