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)

Influenza A and B viruses cause serious, sometimes fatal, disease in immunocompromised patients, particularly bone marrow and solid organ transplant recipients. Protracted disease has also been recognized in certain oncology and HIV-infected patients. Currently available inactivated vaccines are variably immunogenic in such groups. Poor humoral immune responses are seen within 2 years of bone marrow transplantation, often following solid organ transplantation, and commonly in patients with advanced HIV infection. Oral amantadine and rimantadine are useful for prophylaxis and treatment of influenza A virus infections, but their efficacy, particularly in treatment of severe disease, has not been rigorously established in immunocompromised hosts. Case reports document the emergence of drug-resistant variants and prolonged viral shedding in some patients. Aerosol and intravenous ribavirin has been used to treat severe influenza in small numbers of immunosuppressed patients, but the efficacy of ribavirin by either route has not been established in such patients. The neuraminidase inhibitor GG167 is active in experimental influenza but requires topical application to the respiratory tract and has had limited clinical study in natural influenza. More effective interventions for serious influenza infections will likely require combinations of antiviral drugs.
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PMID:Prevention and treatment of influenza in immunocompromised patients. 1086 44

Recent controlled clinical trials have confirmed the usefulness of aerosolized tobramycin in cystic fibrosis and have emphasized the importance of ensuring adequate lung delivery of inhaled antimicrobials. For purulent tracheobronchitis associated with prolonged mechanical ventilation it has recently been established that it is possible to deliver substantial and measurable doses of medications to the airway via aerosolization, but controlled studies are needed to determine the efficacy and safety of inhaled antibiotic therapy in this setting. However, prophylactic aerosolized antibiotic therapy in an intensive care unit setting may be counterproductive. Aerosolized pentamidine continues to provide prophylaxis against PCP in a substantial minority of subjects with human immunodeficiency virus infection who are intolerant of oral agents. The effectiveness of aerosolized amphotericin B as prophylaxis against aspergillosis in neutropenic patients needs to be evaluated in a large clinical trial. Zanamivir, an inhibitor of neuraminidase, delivered via inhalation, shows promise in the treatment of uncomplicated influenza infection, but more data are needed on its effectiveness and safety in patients with preexisting respiratory disease. The development of new chemical entities, more efficient delivery systems, and more precise measurement of dose-response and regional pulmonary drug distribution of inhaled antimicrobials suggest that this somewhat neglected topic in therapeutics may be about to receive an increased degree of attention.
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PMID:Inhaled antimicrobial therapy: from cystic fibrosis to the flu. 1130 34

Neuraminidases, also termed sialidases, which catalyze the removal of sialic acid residues from various glycoconjugates, have been previously reported to modulate HIV-1 replication. Given that some of the known opportunistic microbes found in patients infected with HIV-1 harbor neuraminidase (NA) activity, we speculated that pathogen-derived NA might be envisaged as an important factor in the pathogenesis of this retroviral infection. In the present study, we have monitored the putative modulation of HIV-1-mediated syncytium formation and virus replication by highly purified bacterial-derived NA from Arthrobacter ureafaciens. Taking advantage of a luciferase-based syncytium quantitative assay, we demonstrate here that the level of HIV-1-mediated syncytium formation is enhanced in the presence of NA and that it necessitates interaction between gp120 and CD4/chemokine coreceptor. By using pseudotyped recombinant luciferase-encoding HIV-1 particles, we found that NA treatment of human CD4-positive target cells (i.e., T lymphoid, monocytoid, and peripheral blood mononuclear cells) significantly augmented single-round infection by T- and macrophage-tropic isolates of HIV-1. The observed increase in HIV-1 infection was linked with an enhancement in the initial steps of the virus replicative cycle as monitored by viral binding and entry assays. Interestingly, NA treatment also enhances infectivity of HIV-1 pseudotypes with envelope glycoprotein from the amphotropic murine leukemia virus or the vesicular stomatitis virus. Taken together, our results provide useful information regarding the possible contribution of microbial agents carrying NA activity to HIV-1 pathogenesis.
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PMID:Neuraminidase from a bacterial source enhances both HIV-1-mediated syncytium formation and the virus binding/entry process. 1135 65

The degree of sialylation has been shown previously to modulate the process of human immunodeficiency virus type-1 (HIV-1) infection by affecting the interaction between the virus and CD4-expressing target cells. In the present study, we investigated whether HIV-1 replication cycle was affected by neuraminidase (NA) derived from the human influenza (flu) virus. We first demonstrate that the level of HIV-1-mediated syncytium formation was greatly enhanced in the presence of purified flu NA. Pretreatment of established monocytic and lymphocytic cell lines as well as primary mononuclear cells with purified flu NA augmented also the process of virus infection. A comparable up-regulating effect was observed when using several strains of UV-inactivated whole flu virus, thereby suggesting that virus-anchored NA enzymes positively modulate the HIV-1 life cycle. Furthermore, flu NA-mediated positive effect on HIV-1 biology was abrogated with zanamivir, a specific flu NA inhibitor. Our results provide a new model allowing the investigation of the potential benefit of using NA inhibitors in the treatment of HIV-1-infected patients suffering from coinfection with NA-bearing pathogens.
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PMID:Syncytium formation and HIV-1 replication are both accentuated by purified influenza and virus-associated neuraminidase. 1178 17

We have previously reported that alpha-fetoprotein (AFP) inhibits infection of human monocyte-derived macrophages (MDM) by R5-HIV-1 strains and that a peptide mimicking the clade B HIV-1 gp120 consensus V3 domain (V3Cs) binds to CCR5. We demonstrate here that AFP binds high- and low-affinity binding sites of MDM, characterized, respectively, by 5.15 and 100nM K(d) values. Heat denaturation or neuraminidase treatment of AFP inhibits this binding, suggesting the involvement of protein-protein and lectin-carbohydrate interactions. Moreover, AFP displaces V3Cs binding to MDM. In addition, MIP-1beta, the most specific CCR5 ligand, displaces AFP binding to MDM (IC(50)=4.3nM). Finally, we demonstrate that AFP binds to a ligand of HIV-gp120 V3Cs domain, CCR5, expressed by MDM and by HeLa cells expressing CCR5. Such binding is not observed in the presence of HeLa cells lacking CCR5. The present results provide strong evidence that AFP directly binds to CCR5 expressed by human primary macrophages and by transfected CCR5+ HeLa cells.
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PMID:Human alpha-fetoprotein binds to primary macrophages. 1217 10

The potential of a large variety of new compounds and new strategies for the treatment of virtually all major virus infections has been addressed. This includes, for the treatment of HIV infections, virus adsorption inhibitors (cosalane derivatives, cyanovirin-N), co-receptor antagonists (TAK-779, AMD3100), viral fusion inhibitors (pentafuside T-20, betulinic acid derivatives), viral uncoating inhibitors (azodicarbonamide), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs: emtricitabine, amdoxovir, dOTC, d4TMP prodrugs, tenofovir disoproxil fumarate), non-nucleoside reverse transcriptase inhibitors (NNRTIs: thiocarboxanilide UC-781, capravirine, SJ-3366, DPC 083, TMC 125/R165335), integrase inhibitors (diketo acids), transcription inhibitors (temacrazine, flavopiridol), protease inhibitors (atazanavir, mozenavir, tipranavir); for the treatment of RSV and paramyxovirus infections, viral fusion inhibitors (R170591, VP-14637, NMS03); for the treatment of picornavirus infections, viral uncoating inhibitors (pleconaril); for the treatment of pesti- (hepaci-, flavi-) virus infections, RNA replicase inhibitors (VP-32947); for the treatment of herpesvirus (HSV, VZV, CMV) infections, DNA polymerase inhibitors (A-5021, L- and D-cyclohexenylguanine); for the treatment of VZV infections, bicyclic furopyrimidine analogues; for the treatment of CMV infections, fomivirsen; for the treatment of DNA virus infections at large (papilloma-, polyoma-, herpes-, adeno- and poxvirus infections), cidofovir; for the treatment of influenza, neuraminidase inhibitors (zanamivir, oseltamivir, RWJ-270201); for the treatment of HBV infections, adefovir dipivoxil; for the treatment of HBV and HCV infections, N-glycosylation inhibitors (N-nonyl-deoxynojirimycin); and, finally, IMP dehydrogenase inhibitors and S-adenosylhomocysteine hydrolase inhibitors, for the treatment of various virus infections, including hemorrhagic fever virus infections.
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PMID:Highlights in the development of new antiviral agents. 1237 77

As soluble recognition molecules of innate immunity, C1q and MBL are able to bind directly to various viruses, including retroviruses and influenza viruses. Interaction of C1q with retroviruses and certain infected cells was shown to involve the globular region of C1q and viral envelope glycoproteins, such as p15E of MuLV, gp41 and gp120 of HIV-1, gp21 of HTLV-1. C1q binding was found to trigger antibody-independent activation of the classical pathway of complement, but did not lead to virus destruction and had even an adverse effect on infection in humans, because of subversion of the complement system by the virus. Binding of MBL or of the pulmonary collectin SP-D to influenza A virus was shown to involve the carbohydrate recognition domain of the molecule and high-mannose oligosaccharides of the viral proteins haemagglutinin and neuraminidase. These interactions lead to virus inactivation, are independent of complement activation and are influenced by the oligomerization state of the collectin.
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PMID:Interaction of C1q and mannan-binding lectin with viruses. 1239 16

Mannose-binding lectin (MBL) is a C-type lectin of the innate immune system that binds to carbohydrates on the surface of certain microorganisms. Previous studies showed that MBL binds to gp120, the envelope glycoprotein of HIV-1. gp120 is extensively glycosylated, with N-linked complex and high mannose carbohydrates accounting for about half of the molecular weight. The objectives of this study were to determine the types of glycans on gp120 important for MBL binding and to determine if alteration of complex glycans with neuraminidase (NA) could enhance the interaction of MBL with virus. Lectin blot analyses revealed that MBL interacted with recombinant gp120 (rgp120) from both T cell-tropic and M-tropic virus strains. Treatment of rgp120 with endoglycosidase H (eH) or endoglycosidase F1 (eF1) abrogated binding of MBL, but did not decrease binding of wheat germ agglutinin indicating that high mannose and/or hybrid N-linked glycans were required for MBL binding. Removal of sialic acids from rgp120 with NA enhanced MBL binding. Treatment of intact virus from T cell lines or primary isolates with eF1 also significantly decreased HIV binding to MBL, while treatment with NA substantially increased binding. Treatment of virus with both eF1 and NA did not decrease binding compared to NA alone suggesting that NA treatment exposed binding sites on gp120 that are not high mannose glycans. These studies provide evidence that MBL binds to HIV via high mannose carbohydrates on gp120 and shows that the interaction of MBL with virus is regulated by sialylation.
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PMID:High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1. 1248 19

Mannose-binding lectin (MBL), a C-type lectin component of the human innate immune system, binds to the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). The objective of this study was to assess the effects of inhibitors of endoplasmic reticulum glucosidases and Golgi mannosidase as well as neuraminidase (NA) on the interaction between HIV and MBL. Production of HIV in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) significantly enhanced binding of HIV to MBL and increased MBL neutralization of an M-tropic HIV primary isolate. In contrast, culturing HIV in the presence of alpha-glucosidase I and II inhibitors castanospermine and deoxynojirimycin only slightly affected virus binding and neutralization by MBL. Removal of sialic acid from HIV by NA also significantly enhanced virus binding and neutralization by MBL. Treatment of virus grown in the presence of dMM with endoglycosidase F1 substantially reduced binding to MBL, indicating that dMM increased MBL binding by increasing high-mannose carbohydrates on the virus. In contrast, endoglycosidase F1 did not decrease the MBL interaction with NA-treated virus, suggesting that NA exposed novel MBL binding sites. Treatment with dMM increased the immunocapture of HIV by monoclonal antibodies 2F5 and 2G12, indicating that altering the glycosylation of viral glycoproteins increases the accessibility or reactivity of some epitopes. This study shows that specific alterations of the N-linked carbohydrates on HIV gp120/gp41 can enhance MBL-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL.
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PMID:Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. 1256 May 67

The incidence of lower respiratory tract infection (LRTI) in women of child-bearing age is approximately 64 per 1000 population. The spectrum of illness ranges from acute bronchitis, which is very common, through influenza virus infection and exacerbations of underlying lung disease, to pneumonia, which, fortunately is uncommon (<1.5% LRTI), but can be severe. Acute bronchitis is generally mild, self-limiting and usually does not require antibacterial therapy. Influenza virus infection in pregnant women has been recently related to increased hospitalization for acute cardiorespiratory conditions. At present, the safety of the newer neuraminidase inhibitors for the treatment of influenza virus infection has not been established in pregnancy and they are not routinely recommended. In influenza virus infection complicated by pneumonia, antibacterial agents active against Staphylococcus aureus and Streptococcus pneumoniae superinfection should be used. There are few data on infective complications of asthma or COPD in pregnancy. The latter is rare, as patients with COPD are usually male and aged over 45 years. Management is the same as for nonpregnant patients. The incidence and mortality of pneumonia in pregnancy is similar to that in nonpregnant patients. Infants born to pregnant patients with pneumonia have been found to be born earlier and weigh less than controls. Risk factors for the development of pneumonia include anemia, asthma and use of antepartum corticosteroids and tocolytic agents. Based on the few available studies, the main pathogens causing pneumonia are S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and viruses. Beta-Lactam and macrolide antibiotics therefore remain the antibiotics of choice in terms of both pathogen coverage and safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial pneumonia, but not Pneumocystis carinii pneumonia (PCP), is more common than in nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not definitely been associated with adverse clinical outcomes despite theoretical risks. Currently it is still the treatment of choice in PCP, where mortality remains high. In conclusion, there are few data specifically related to pregnant women with different types of LRTI. Where data are available, no significant differences compared with nonpregnant patients have been identified. In considering the use of any therapeutic agent or investigation in pregnant patients with LRTI, safety aspects must be carefully weighed against potential benefit. Otherwise, management strategies should not differ from those for nonpregnant patients. Further research in this area is warranted.
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PMID:Treatment of community-acquired lower respiratory tract infections during pregnancy. 1472 4


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