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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunoglobulins are plasma derivatives with a low risk of transmitting viral infections. To the present, no proven case of human immunoglobulins transmitting human immunodeficiency viruses has been reported. However, there have been a few reports on the transmission of hepatitis C virus by these plasma proteins. To improve further the safety of both 5s iv human immunoglobulins and 7s im immunoglobulins, we introduced a 10-hour heat treatment of the aqueous solutions at 60 degrees C (i.e., pasteurization) into the manufacturing procedure. This treatment was not added to the manufacturing procedure of 7s iv immunoglobulin that already contained the S-sulfonation as a virus inactivating method. We now report on experimental data that show that the whole manufacturing procedures of the above immunoglobulins inactivate efficiently hepatitis C virus and that the specific virus inactivation methods alone, namely, pasteurization or S-sulfonation, also inactivate completely viruses of the flavivirus family, to which the hepatitis C virus belongs. The inactivation of the Flaviviridae bovine viral diarrhea virus, tick-borne encephalitis virus, and yellow fever virus by pasteurization or S-sulfonation was at least 10(5). The clearance of HCV achieved by the entire manufacturing process of each of these immunoglobulins was also at least 10(5). The experiments therefore show that pasteurization or S-sulfonation provides a high margin of safety to human immunoglobulins regarding the transmission of hepatitis C virus.
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PMID:Virus safety of human immunoglobulins: efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure. 131 86

This article reviews some of the published applications of flow cytometry for in vitro and in vivo detection and enumeration of virus-infected cells. Sample preparation, fixation, and permeabilization techniques for a number of virus-cell systems are evaluated. The use of flow cytometry for multiparameter analysis of virus-cell interactions for simian virus 40, herpes simplex viruses, human cytomegalovirus, and human immunodeficiency virus and its use for determining the effect of antiviral compounds on these virus-infected cells are reviewed. This is followed by a brief description of the use of flow cytometry for the analysis of several virus-infected cell systems, including blue tongue virus, hepatitis C virus, avian reticuloendotheliosis virus, African swine fever virus, woodchuck hepatitis virus, bovine viral diarrhea virus, feline leukemia virus, Epstein-Barr virus, Autographa californica nuclear polyhedrosis virus, and Friend murine leukemia virus. Finally, the use of flow cytometry for the rapid diagnosis of human cytomegalovirus and human immunodeficiency virus in peripheral blood cells of acutely infected patients and the use of this technology to monitor patients on antiviral therapy are reviewed. Future prospects for the rapid diagnosis of in vivo viral and bacterial infections by flow cytometry are discussed.
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PMID:Uses of flow cytometry in virology. 753 May 94

We have validated the use of two new regenerated multilayered structured cellulose membranes (BMM), Planova 15 N and Planova 35 N, with respective mean pore sizes of 15 and 35 nm, as a new filtration system to eliminate viruses in highly purified factor IX and factor XI concentrates. Virus spiking experiments indicated that single dead-end filtration on the membranes could remove more than 5.7-7.8 log10 of human immunodeficiency virus, bovine viral diarrhoea virus, porcine pseudorabies virus, reovirus type 3, and simian virus 40, as well as the small non-enveloped viruses, poliovirus Sabin type 1 and bovine parvovirus. In vitro control tests and animal studies (Wessler stasis model, rat hypotension model) of the two concentrates did not reveal any significant differences with the non-nanofiltered material. Viral filtration of plasma derivatives on porous polymeric membranes might be an essential step in the improvement of their viral safety.
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PMID:Nanofiltration, a new specific virus elimination method applied to high-purity factor IX and factor XI concentrates. 780 1

Intravenous immunoglobulins and serum protein solutions are manufactured from human plasma pools of healthy, screened donors. A step-by-step validation of virus removal and/or inactivation was performed for the manufacturing process, which includes cold ethanol fractionation, beta-propiolactone (beta-PL) treatment, UV irradiation, thermal inactivation and other chemical and physical purification steps. The total viral clearance factors achieved for the entire manufacturing process were by several magnitudes greater than the potential virus load of current plasma pools. Human immunodeficiency virus 1 (HIV-1) infectivity was reduced by > 13.4 log for 7S immunoglobulin, > 15.3 log for IGM enriched immunoglobulin and > 16 log for a 5% serum protein solution. In addition, high clearance rate for a broad spectrum of model viruses was demonstrated for all three blood derivatives being > 23.2 to > 27.8 log for pseudo rabies virus (PSR), > 12.3 to > 22.6 log for vesicular stomatitis virus (VSV) and 6.9-10.6 log for simian virus 40 (SV40). For the beta-propiolactone inactivation step Hepatitis C model viruses, e.g. equine arteritis virus (EAV) and bovine viral diarrhoea virus (BVDV) were also investigated.
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PMID:Validation of virus inactivation and removal for the manufacturing procedure of two immunoglobulins and a 5% serum protein solution treated with beta-propiolactone. 811 39

With the increasing availability of human plasma this source was used to substitute for the production of factor XIII concentrate from placenta. Prior to changing the source material, the virus safety in accordance with the Committee for Proprietary Medicinal Products (CPMP) guidelines and the half-life were investigated. Concerning the virus safety, the following cumulative log 10 clearance factors were obtained: human immunodeficiency virus (HIV) > or = 18.9, herpes simplex virus (HSV-1) > or = 21.5, polio > or = 19.1, bovine viral diarrhea virus (BVDV) > or = 13.3. Half-life studies of factor XIII from plasma in comparison with factor XIII from placenta were done in rabbits by determination of the antigen and in patients with congenital factor XIII deficiency by determination of the activity and antigen. In rabbits, the terminal half-life of the antigen was 78.2 hours for factor XIII from placenta and 87.0 hours for factor XIII from plasma. In patients the half-lives were similar: 9.2 days for activity and antigen of factor XIII from plasma and 8.5 days (activity) versus 9.4 days (antigen) for the placenta-derived factor XIII. Some further clinical studies with factor XIII concentrates are also reviewed. Newer developments concerning recombinant factor XIII, its expression, characterization, and properties are summarized. Concerning the physicochemical data, the behavior in plasma was characterized by the formation of high-molecular-weight complexes, and first in vivo results, the recombinant factor XIII product was comparable to the naturally occurring material.
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PMID:Therapeutic factor XIII preparations and perspectives for recombinant factor XIII. 898 27

The present study was designed to evaluate the effect of bovine immunodeficiency virus (BIV) infection on immune functions and possible interactions between BIV and other bovine viruses in calves. Ten calves were inoculated intravenously with BIV, and five served as controls. An increased lymphocyte proliferation to BIV gag protein was demonstrated 2 to 6 weeks after BIV inoculation (P < 0.05). Lymphocyte subset differentiation revealed a decreased CD4/CD8 ratio (P < 0.05) during weeks 2 to 7, suggesting a possible immune dysfunction in BIV-infected calves. When the calves were inoculated with bovine herpesvirus type 1 (BHV-1), the antibody response to BHV-1 in BIV-infected calves was delayed and the antibody titers were significantly lower (P < 0.05). Injection of bovine viral diarrhea virus vaccine also elicited a lower neutralizing antibody response in BIV-infected calves. The results indicated that immune suppression occurred in BIV-infected calves.
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PMID:Immune suppression in calves with bovine immunodeficiency virus. 906 63

N-Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One function is to assist in the folding of proteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the alpha-glucosidases and this causes some proteins to be misfolded and retained within the endoplasmic reticulum. In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) the misfolding of key viral envelope glycoproteins interferes with the viral life cycle. It has been demonstrated in an animal model of chronic HBV that glucosidase inhibitors can alter glycosylation and have anti-viral activity. As the mechanism of action of alpha-glucosidase inhibitors is the induction of misfolded or otherwise defective viral glycoproteins, such inhibitors may be useful therapeutics for many viruses, especially those which bud from the endoplasmic reticulum (where protein folding takes place). For example bovine viral diarrhea virus, a pestivirus akin to hepatitis C virus, is also extremely sensitive to glucosidase inhibition.
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PMID:Alpha-glucosidase inhibitors as potential broad based anti-viral agents. 967 87

To determine the efficacy of a clean-in-place system for the inactivation of viruses present in human plasma, the effect of 0.1 M sodium hydroxide at 60 degrees C on viral infectivity was investigated. Inactivation of the following model and relevant viruses were followed as a function of time: human hepatitis A virus (HAV), canine parvovirus (CPV; a model for human parvovirus B-19) pseudorabies virus (PRV, a model for hepatitis B virus), and bovine viral diarrhoea virus (BVDV, a model for hepatitis C virus and human immunodeficiency virus). Infectivity of CPV was determined by a novel in situ EIA method which will prove useful for studies to validate parvovirus inactivation or removal. Infectivity of BVDV, PRV and CPV were shown to be reproducibly inactivated below the limit of detection by 0.1 M NaOH at 60 degrees C within 30 s. HAV was inactivated to below the limit of detection within 2 min. Treatment with heat alone also resulted in some log reduction for all viruses tested except for CPV which remained unaffected after heating at 60 degrees C for 16 min. Treatment of HAV with hydroxide alone (up to 1.0 m) at 15 degrees C did not lead to rapid inactivation. Collectively, these data suggest that 0.1 M NaOH at 60 degrees C for two min should be sufficient to inactivate viruses present in process residues.
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PMID:Inactivation kinetics of model and relevant blood-borne viruses by treatment with sodium hydroxide and heat. 1020 25

To assess the virus reducing capacity of Cohn's cold ethanol fractionation process for the production of intravenous (IVIg) and intramuscular (IMIg) immunoglobulin products, and treatment of these products at pH 4, a validation study of virus removal and/or inactivation was performed using both lipid-enveloped viruses [human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV) and pseudorabies virus (PSR)], and non-lipid-enveloped viruses [(simian virus 40 (SV40) and encephalomyocarditis virus (EMC)]. For the cold ethanol fractionation process, overall reduction factors of 3.0 logs, > or = 2.6 (< 5.5) logs, 4.6 logs, 5.8 logs and > or = 2.6 (< 6.2) logs were found for HIV, BVDV, PSR, SV40 and EMC, respectively. For all tested viruses the precipitation of fraction III from fraction II + III was the most effective step. From the overall reduction factors it appears that cold ethanol fractionation, although capable of reducing viral infectivity to a significant extent, is not sufficient to meet the requirements of regulatory bodies for viral safety of immunoglobulin products. However, pH 4 treatment contributes effectively to the viral safety of the final products. Treatment at pH 4.05 and 37 degrees C for 16 h, as is applied to IVIg, yields reduction factors of > or = 8.4 logs, > or = 4.0 logs, > or = 7.1 logs, 4.8 logs and 1.4 logs for HIV, BVDV, PSR, SV40 and EMC, respectively. The effectiveness of this process step could be enhanced by extending incubation to 40 h at pH 4.25 compared to 16 h at pH 4.05. The extended incubation, as applied in the production of IMIg, yields a reduction of infectivity of SV40 by > or = 5.5 (< 8.0) logs and of EMC by > or = 4.1 (< 7.1) logs. Storage of IMIg, which is formulated as a solution, at 2-8 degrees C also contributes to virus safety. For storage periods of 8 weeks or longer, reduction factors of 2 to 6 logs were found for all viruses, except for BVDV which remained unaffected. These data indicate that the production processes for IVIg and IMIg as described here have sufficient virus reducing capacity to achieve a high margin of virus safety.
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PMID:Virus validation of pH 4-treated human immunoglobulin products produced by the Cohn fractionation process. 1040 30

Photodynamically induced virus inactivation appears promising in preventing transmission of enveloped virus infections in transfusible blood products. The potential for utilizing hypericin as a photosensitizer to inactivate key enveloped viruses in packed red cell concentrates (PRC) was evaluated. In addition to inactivating effectively > or = 10(6) TCID50 of human immunodeficiency virus (HIV), inactivation of bovine viral diarrhea virus (BVDV) in PRC was used as a model for hepatitis C virus to overcome the deficiency in reliable experimental systems for hepatitis C virus (HCV) inactivation. BVDV was two orders of magnitude more sensitive to inactivation by hypericin than HIV. As part of the virucidal efficacy analyses, the effects of photosensitization on hemopoietic cell lines carrying quiescent integrated HIV provirus were studied as models for evaluating virus inactivation in latently infected cells. Phorbol ester-induced virus production by these cells was effectively prevented by photosensitization with hypericin. A refinement of the illumination conditions, incorporating a monochromatic sodium light source with an emission spectrum coinciding with the absorption peak of hypericin, was highly virucidal, however, caused unacceptable levels of hemolysis. Red blood cells could be protected from phototoxic cellular damage by complexing hypericin with human serum albumin (albumin-hypericin), but the decrease in hemolysis was at the expense of virucidal efficacy. Thus, excitation of hypericin with a fluorescent source appears to be useful potentially for virus inactivation in PRC.
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PMID:Strategies for evaluation of enveloped virus inactivation in red cell concentrates using hypericin. 1068 93


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