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PubMedDate not supplied

Characterization of highly purified, inactivated HIV-1 particles isolated by anion exchange chromatography.

This report characterizes inactivated, gp120 depleted, HIV-1 particles purified by an anion exchange chromatography production process. This antigen formulated with incomplete Freund's adjuvant constitutes Remune, which is being evaluated in a phase III clinical endpoint trial to determine the effect of this immune-based therapy on clinical progression of HIV-1 seropositive patients. Multiple production lots of the inactivated HIV-1 antigen strain HZ321, isolated by anion exchange chromatography, exhibit purity of > 95% by gel filtration. These findings are corroborated by thin section electron microscopy showing a homogenous field of intact particles. Analyses of the purified virus particles for protein, lipid, carbohydrate and RNA show structural retention of the envelope proteins, lipid bilayer and core components after large scale processing. The qualitative identification of at least 85% of total HIV-1 protein is determined by ELISA, Western blot, HPLC and amino acid sequencing analyses. Quantitative values are assigned to 50% of these proteins. The data confirm the presence of virally encoded proteins p6, p7, pI15, p17, p24, p32, pI39Gag, gp41, pp55Gag, p66/51, Vpr, Vif and Nef. Excellent consistency between production lots and equivalency to HIV-1 preparations purified by sucrose density gradient sedimentation has been established for protein and lipid composition, and overall purity. These findings further establish that non-viral encoded proteins and lipids are integral structural components of the intact virion and are not contaminants unique to a particular isolation method. The data confirm the presence of multicomponent antigens in the viral particles for stimulating a broad HIV-1 specific immune response. Finally, the work demonstrates that the two inactivation procedures (beta-propiolactone and gamma irradiation), which achieve efficient viral inactivation meeting US FDA guidelines, do not damage the protein antigens of the viral particles.

Carbohydrates↗
PubMed1999

Impact of dimethyl sulfoxide and examples of combined genotoxicity in the SOS chromotest.

The bacterial SOS chromotest with Escherichia coli PQ37 was used for the assessment of genotoxicity of combined xenobiotic treatments. The modulation of test compound genotoxicity by dimethyl sulfoxide (DMSO), a common solvent for test compounds, was assessed as well. It was shown that DMSO modulated SOS chromotest genotoxicity of several xenobiotics: in comparison to test compound dissolution in water, the commonly used addition of 3.2% (v/v) DMSO as solvent lead to a significant increase in the genotoxicity of K(2)RhCl(5) and beta-propiolactone (BPL). However, the effects of cisplatin decreased significantly when DMSO was added. Thus, albeit DMSO is not genotoxic in this test itself, it can interfere with SOS chromotest responses. Further experiments were performed in the absence of DMSO. BPL and cisplatin in combination showed an over-additive synergism in SOS genotoxicity as well as K(2)RhCl(5) and cisplatin did. Addition of Pd(NH(3))(4)Cl(2) and NaAsO(2), which are non-genotoxic in the SOS chromotest, did not enhance the K(2)RhCl(5)- or BPL-mediated SOS sfiA induction. Nevertheless, at the highest subcytotoxic dose of NaAsO(2) tested (200 microM), a slight yet significant suppression of BPL-mediated SOS genotoxicity was observed. These results confirm that the SOS chromotest is a useful tool for the rapid evaluation of the combined genotoxicity of compound mixtures. However, the use of DMSO as test solvent has to be taken with caution.

Cisplatin↗
PubMed1982

Two DNA glycosylases in Escherichia coli which release primarily 3-methyladenine.

Two enzymes have been partially purified from Escherichia coli and designated 3-methyladenine DNA glycosylases I and II. The glycosylase I is that described by Riazuddin & Lindahl [Riazuddin, S., & Lindahl, T. (1978) Biochemistry 17, 2110-2118]. The apparent molecular weight of glycosylase I is 20 000, and that of II is 27 000. Glycosylase I releases 3-methyladenine (3-MeA) while II releases 3-MeA, 3-methylguanine (3-MeG), 7-methylguanine (7-MeG), and 7-methyladenine (7-MeA). The rate of release of 3-MeA by glycosylase II is 30 times that of 7-MeG. Glycosylase I is missing in mutants tag 1 and tag 2 [Karran, P., Lindahl, T., Ofsteng, I., Evenson, G. B., & Seeberg, E. (1980) J. Mol. Biol. 140, 101-127]. In crude extracts, the 3-MeA activity of II is approximately 10% of the total 3-MeA activity. A 50% inactivation at 48 degrees C required 5 min for I and 65 min for II. The apparent Km for 3-MeA residues for glycosylase I was 1.4 x 10(-8) M. The enzyme was inhibited noncompetitively by 3-MeA with an average apparent Ki of 1.6 mM. The apparent Km for 3-MeA, for glycosylase II, was 9.2 x 10(-9)M, and it was not inhibited by 3-MeA. The 3-MeA and 7-MeG activities of the glycosylase II preparation could not be separated by isoelectric focusing, by chromatography on DEAE, Sephadex G-100, phosphocellulose, DNA-cellulose, or carboxymethylcellulose, or by heating at 50 degrees C. The apparent Km for 7-MeG was 1.1 x 10(-8)M. Glycosylase II released N1-(carboxyethyl)adenine and N7-(carboxymethyl)guanine from DNA treated with beta-[3H]propiolactone but did not release the aflatoxin B-1 adduct at N-7 of guanine.

Adenine↗
PubMed1980

Estimation of apurinic/apyrimidinic sites and phosphotriesters in deoxyribonucleic acid treated with electrophilic carcinogens and mutagens.

The number of apurinic/apyrimidinic (AP) sites in supercoiled SV40 deoxyribonucleic acid (DNA) after treatment with several electrophilic mutagens was quantitated by electrophoretic analysis of the DNA after cleavage of the phosphodiester bonds adjacent to AP sites by a specific endonuclease. The compounds studied, in order of increasing yields of AP sites obtained on incubation with the DNA for 5 h at 37 degrees C, were dimethylcarbamoyl chloride, ethyl methanesulfonate, N-ethyl-N-nitrosourea, 2-(N-acetoxyacetylamino)fluorene, beta-propiolactone, N-methyl-N-nitrosourea, methyl methanesulfonate, 1'-acetoxyestragole, 4-(N-acetoxyacetylamino)stilbene, (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, N-(benzoyloxy)-N-methyl-4-aminoazobenzene, and 1-pyrenyloxirane. After a 5-h incubation at 37 degrees C and extraction of unreacted compound, further incubation at 70 degrees C generally increased the yield of AP sites; an exception was N-(benzoyloxy)-N-methyl-4-aminoazobenzene-reacted DNA. Except for DNA treated with N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea, which are known to bind to a significant extent to DNA phosphates, the number of alkali-labile lesions in the treated DNA was similar to the number of AP sites. For the compounds studied there was no direct correlation between the number of AP sites produced and missense mutagenic activity, as measured in Salmonella typhimurium strain TA100.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMedDate not supplied

Correlation between structure of the lactones and substrate specificity in enzyme-catalyzed polymerization for the synthesis of polyesters.

Small-size (4-membered) and medium-size (5-, 6-, and 7-membered) unsubstituted lactones as well as unsubstituted macrolides (12 and 13 membered) were subjected to the ring-opening polymerization using the extracellular PHB depolymerase from Alcaligenes faecalis T1 (PhaZ(Afa)). The characteristic reactivities of the lactones were discussed based on a tertiary structure model of the active site of the PhaZ(Afa). With respect to the ring-size of the lactones, the 4-membered beta-propiolactone and 6-membered delta-valerolactone (delta-VL) showed the highest polymerization activity, and delta-VL seemed to be the upper size limit for the molecular recognition of the narrow active site cleft of PhaZ(Afa). On the other hand, epsilon-caprolactone, 11-undecanolide, and 12-dodecanolide, which showed excellent polymerization activities by lipases, were scarcely polymerized by PhaZ(Afa). This was ascribed to the difference in the recognition sites between PhaZ(Afa) and lipase. In addition, the effect of the substrate-binding domain of PhaZ(Afa) and the enantioselective ring-opening polymerization of (R,S)-beta-butyrolactone ((R,S)-beta-BL) were studied. The substrate-binding domain lacking PhaZ(Afa) showed higher reactivities than PhaZ(Afa) for the polymerization of the lactones and that a significant enantioselectivity was observed at the early stage of the polymerization of (R,S)-beta-BL to produce the (R)-enriched optically active poly(3-hydroxybutyrate).

Acyltransferases↗
PubMed2002

Conformation-dependent reaction thermochemistry: study of lactones and lactone enolates in the gas phase.

Gas-phase acidities (Delta H degrees (acid)) of lactones with ring sizes from four to seven have been measured on a Fourier transform ion cyclotron resonance mass spectrometer. Electron affinities (EAs) of the corresponding lactone enolate radicals were measured on a continuous-wave ion cyclotron resonance mass spectrometer, and the bond dissociation energies (BDEs) of the alpha C-H bonds were derived. In order of increasing ring size, Delta H degrees (acid) = 368.7 +/- 2., 369.4 +/- 2.2, 367.3 +/- 2.2, and 368.3 +/- 2.2 kcal/mol and BDE = 99.4 +/- 2.3, 94.8 +/- 2.3, 89.2 +/- 2.3, and 92.8 +/- 2.4 kcal/mol for beta-propiolactone, gamma-butyrolactone, delta-valerolactone, and epsilon-caprolactone, respectively. For their corresponding enolate radicals, EA = 44.1 +/- 0.3, 38.8 +/- 0.3, 35.3 +/- 0.3, and 37.9 +/- 0.6 kcal/mol. All of these lactones are considerably more acidic than methyl acetate, consistent with a dipole repulsion model. Both BDEs and EAs show a strong dependence on ring size, whereas Delta H degrees (acid) does not. These findings are discussed, taking into account differential electronic effects and differential strain between the reactant and product species in each reaction.

Journal Article↗
PubMed2005

Reactivity of lactones and GHB formation.

The behavior of lactones in their hydrolysis reactions is a good indicator of their reactivity as electrophilic molecules. The hydrolysis of four- to six-membered lactones was investigated in neutral (water) and slightly acid media and in water/dioxane media. The following conclusions were drawn: (i) The reactivity of beta-propiolactone in neutral water is more than four times greater than that of beta-butyrolactone, due to the flow of charge caused by the latter's methyl substituent. Reactivity is enthalpy-controlled. (ii) The reactivity of beta-lactones diminishes in water/dioxane media when the percentage of dioxane increases. The increase in the dioxane percentage relaxing the intermolecular hydrogen bonds in the ordered structure of the water reduces DeltaH# and simultaneously increases the -DeltaS# value. (iii) An inverse solvent kinetic isotope effect in the acid-catalyzed hydrolysis of gamma-butyrolactone and delta-valerolactone was observed, this being indicative of acyl cleavage. (iv) The DeltaH# and DeltaS# values permit discrimination between alkyl and acyl cleavage. (v) A correlation was found between the chemical reactivity of lactones and their carcinogenic activity. (vi) The results suggest that orally ingested gamma-butyrolactone remains largely in its nonhydrolyzed form in the stomach before passing into the blood. (vii) The concentration equilibrium constant of GHB formation at human body temperature is Keq (37 degrees C)=0.40. (viii) Study of GHB formation shows that, contrary to earlier results, this is an endothermic process, with DeltarH=3.6 kJ mol(-1).

Animals↗
PubMed2006

Structures of heterogeneous proton-bond dimers with a high dipole moment monomer: covalent vs electrostatic interactions.

A number of calculated structures of heterogeneous proton-bound dimers containing monomers such as acetonitrile, cyanamide, vinylene carbonate, and propiolactone, which have high dipole moments, are presented. These proton-bound dimers are predicted to have a structural anomaly pertaining to the bond distances between the central proton and the basic sites on each of the monomers. The monomers with the high dipole moments also have the larger proton affinity and, on the basis of difference in proton affinities, it would be expected that the proton would be closer to this monomer than the one with the lower proton affinity. However, the proton is found to lie substantially closer to the monomer with the lower proton affinity in most cases, unless the difference in proton affinity is too large. Simply stated, the difference in proton affinities is smaller than the difference in the affinity to form an ion-dipole complex for the two monomers and it is the larger affinity for the high dipole moment monomer (which also has the higher proton affinity) to form an ion-dipole complex that is responsible for the proton lying closer to the low proton affinity monomer. The bond distances between the central proton and the monomers are found to be related to the difference in proton affinity. It is found, though, that the proton-bound dimers can be grouped into two separate groups, one where the proton-bound dimer contains a high dipole moment monomer and one group where the proton-bound dimer does not contain a high dipole moment monomer. From these plots it has been determined that a high dipole moment monomer is one that has a dipole moment greater than 2.9 D.

Journal Article↗
PubMed2005

A kinetic approach to the alkylating potential of carcinogenic lactones.

The alkylating potential of beta-propiolactone (BPL), beta-butyrolactone (BBL), gamma-butyrolactone, and delta-valerolactone, which can be formed by the in vivo nitrosation of primary amino acids, was investigated kinetically. The nucleophile NBP, 4-(p-nitrobenzyl)pyridine, a trap for alkylating agents, was used as an alkylation substrate. The alkylation reactions were performed under mimicked cellular conditions at neutral pH in water/dioxane solvent mixtures. To gain insight into the effect of the hydrolysis of lactones on their alkylating efficiency, alkylation and competing hydrolysis were studied in parallel. Conclusions were drawn as follows: (i) gamma-Butyrolactone and delta-valerolactone afford neither appreciable NBP alkylation nor hydrolysis reactions; (ii) the alkylating potential of BPL is 10-fold higher than that of BBL, the reactivity of both being essentially enthalpy-controlled; (iii) a correlation was found between the alkylating potential of lactones and their carcinogenicity; (iv) the hydrolysis of lactones is not sufficiently effective to prevent alkylation; (v) the efficiency of alkylation, expressed as the alkylation rate/hydrolysis rate ratio, decreases strongly with increasing amounts of dioxane in the reaction media; (vi) the absorption coefficients of the NBP-lactone adducts are as follows: epsilon(NBP-BPL) = 5101 +/- 111 M(-1) cm(-1) (lambda = 584 nm) and epsilon(NBP-BBL) = 462 +/- 19 M(-1) cm(-1) (lambda = 586 nm), the pronounced difference between these values being rationalized in terms of the adducts' structure; and (vii) linear correlations exist between the adducts' absorption coefficients and the water/dioxane ratio in the reaction media.

Alkylation↗
PubMed2005

Characterization of different strains of poliovirus and influenza virus by differential scanning calorimetry.

Vaccines against poliomyelitis and influenza contain inactivated forms of poliovirus and influenza virus. These antigens are generated on an industrial scale from the purified active viruses that have been analysed in this study by DSC (differential scanning calorimetry). Multiple unfolding transitions are seen for influenza virus A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) and B/Shangdong/7/97. These data, combined with previously reported data on other influenza viruses, indicates that each influenza virus strain has a characteristic unfolding behaviour. Only minor changes were seen in the thermogram of betaPL (beta-propiolactone)-inactivated influenza virus, which is consistent with the proposition that betaPL reacts mainly with the nucleotide fraction of the virus. We demonstrate that a peak annotation of the thermogram of the native virus is possible using bromelain-treated virus and virosomes. At pH 1.5-2.5, poliovirus of type I unfolds in a single unfolding event with respective Tm (midpoint of protein unfolding transition) values between 34 and 45 degrees C. At pH 2, polioviruses of type II unfold equally in a single event, but, compared with the type I virus, with a Tm value increased by 3.7 degrees C. At neutral pH, the DSC thermogram of type I poliovirus was very 'noisy'. Data obtained offer the possibility of precisely characterizing and identifying different viral strains.

Bromelains↗
PubMed1998

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen, II. Cellular, but not humoral, systemic immune responses against rabies virus immune-stimulating complexes are macrophage dependent.

In this paper we describe the effect of depletion of splenic macrophages on the uptake, and immune response against, different formulations of rabies virus antigen. Splenic macrophages were removed by intravenous injection with clodronate liposomes. beta-propiolacton inactivated rabies virus (RV-BPL) and immune-stimulating complexes (iscom) containing these antigens were given to macrophage-depleted and control mice. In the absence of phagocytic cells in the spleen, antigen is still trapped in the red pulp and to a lesser extent in the peri-arteriolar lymphocyte sheaths (PALS) for both antigen formulations. The localization pattern in the main area of immune response induction, namely the follicles, was unaltered after macrophage depletion. Functionally, the depletion of splenic and liver macrophages had no influence on the induction of specific antibody responses in both RV-BPL or RV-iscom immunized mice, even though the latter presentation form was clearly associated with specific localization in the marginal metallophillic macrophages. In RV-BPL immunized mice, macrophage depletion had no influence on proliferative T-cell responses. However, macrophage-depleted mice that were immunized with RV-iscom showed a significant decrease in proliferative T-cell responses. These results confirm existing ideas on the spleen as a physical filter rather than an induction site for humoral responses and shed new light on the efficient role of iscoms as antigen-presenting moieties in relation to their specific in vivo localization patterns and partial macrophage dependency.

Animals↗
PubMedDate not supplied

Inactivation of human T-cell lymphotropic virus, type III by heat, chemicals, and irradiation.

Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was inactivated by heat more rapidly if in liquid medium than if lyophilized and more rapidly at 60 degrees than 56 degrees C. When HTLV-III was added to factor VIII suspension, then lyophilized and heated at 60 degrees C for 2 hours or longer there was elimination of 1 X 10(6) in vitro infectious units (IVIU) of virus. Much of the viral inactivation appeared to result from lyophilization. The application of water-saturated chloroform to the lyophilized material containing virus also resulted in elimination of infectivity. HTLV-III was efficiently inactivated by formalin, beta-propiolactone, ethyl ether, detergent, and ultraviolet light plus psoralen. The results are reassuring regarding the potential safety of various biological products.

Chloroform↗
PubMedDate not supplied

[Prevention of cytomegalic inclusion disease in leukemia patients with a cytomegalovirus hyperimmune globulin preparation].

In a randomised study the efficacy of a cytomegalic hyperimmune globulin preparation (CMV-HIGP) which had been treated with beta-propiolactone was analysed. The study included 85 patients with acute lymphoblastic leukemia (ALL) and Non-B-Non-Hodgkin-lymphoma (NHL) who were treated initially or underwent a relapse therapy. During the intense chemotherapeutical period within leukemia treatment the patients were passively immunised by the intravenous route with CMV-HIGP (1 ml per kilogram of body weight) every two to three weeks at the latest. In the initial stages the basic immunisation protection was achieved by the application of double dose CMV-HIGP. The Frankfurt patients were recruited from the BFM-ALL- and the NHL-study since october 1982. When they were admitted their CMV serostatus was determined by means of the ELA-ELISA or IFA-method. Seronegative patients were given the passive immunisation immediately or 48 hours after the first blood transfusions at the latest. The patients who had become CMV-IgG-positive by passive immunisation were randomised when reaching long-term therapy according to the protocol. Because of a 30% cytomegaly disease incidence rate in our patient population a randomisation was unwarrantable at the beginning of leukemia treatment. During randomisation one group of patients were immunised by the intravenous route with CMV-HIGP (2 ml per kg body weight one time in four weeks), the second group was a control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1974

Establishment of a tetraploid, immunoglobulin-producing cell line from the hybridization of two human lymphocyte lines.

We here report the establishment of a seemingly permanent hybrid cell line formed by fusion of the cells of two biochemically mutant human lymphocyte lines. One parental line (UM-1-6TGr) was deficient in hypoxanthine-guanine phosphoribosyl transferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), and had two marker chromosomes. The second parental line (UM-21-5) was a clonal derivative of a citrullinemic lymphocyte line, and was, like the line of origin, dificient in argininosuccinic acid synthetase [(L)-Citrulline: (L)-aspartate ligase (AMP-forming), EC 6.3.4.5]. This line also had a marker chromosome, which was a B5 with a very prominent secondary constriction. After trypsinization of both parental lines, followed by addition to the fusion mixture of beta-propiolactone-inactivated Sendai virus, the cells were placed in a doubly selective medium (hypoxanthine-aminopterin-thymidine-containing medium in which the arginine was replaced with citrulline) to prevent the proliferation of the mutant parents. Under selective conditions, 97-99% of cells were found to be tetraploid, containing the three marker chromosomes; and the specific activities of the hybrid line transferase and synthetase were intermediate between normal and mutant line values. Furthermore, the UM-1-6TGr and UM-21-5 lines were producers of gamma and mu heavy chains of immunoglobulin, and of kappa light chains, as determined by immunodiffusion and immunofluorescence, and the hybrid line continued to synthesize and to secrete detectable levels of these same immunoglobulins. These studies demonstrate the genic and cytogenetic stability of this hybridized lymphocyte cell line, and prove that hybridization per se does not extinguish the activity of either the regulatory of structural genes involved in immunoglobulin synthesis.

Cell Fusion↗
PubMed1976

Release by human chromosome 3 of the block at G1 of the cell cycle, in hybrids between tsAF8 hamster and human cells.

A temperature-sensitive mutant of Syrian hamster cells, AF8 was fused with simian-virus-40-transformed Lesch-Nyhan fibroblasts; LNSV, in the presence of beta-propiolactone-inactivated Sendai virus. The AF8 cells grow well at 33.5 degrees but are arrested in mid G1 period when shifted to 39 degrees. The LNSV cells are deficient in hypoxanthine guanine phosphoribosyltransferase. The hybrid clones were selected in hypoxanthine-aminopterin-thymidine medium at 39 degrees. A total of 20 clones was isolated and karyotyped. All clones contained most of the hamster chromosomes and one to eight human chromosomes. The preferential retention of human chromosome 3 was observed in 100% of the metaphases of all clones. In nine of the clones, the only human chromosome present was chromosome 3. The results indicate that human chromosome 3 is responsible for conferring to the hybrid cells the ability to grow at nonpermissive temperature for AF8 cells, i.e., the ability to overcome the G1 block. These findings, together with other reports in the cell cycle may be regulated by genes located on different chromosomes.

Antigens, Viral↗
PubMed1981

32P-labeling test for DNA damage.

Covalent adducts formed by the reaction of DNA with chemical carcinogens and mutagens may be detected by a 32P-labeling test. DNA preparations exposed to chemicals known to bind covalently to DNA [N-methyl-N-nitrosourea, dimethyl sulfate, formaldehyde, beta-propiolactone, propylene oxide, streptozotocin, nitrogen mustard, and 1,3-bis(2-chloroethyl)-1-nitrosourea] were digested to a mixture of deoxynucleoside 3'-monophosphates by incubation with micrococcal endonuclease (EC 3.1.31.1) and spleen exonuclease (EC 3.1.16.1). The digests were treated with [gamma-32P]ATP and T4 polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) to convert the monophosphates to 5'-32P-labeled deoxynucleoside 3',5'-bis-phosphates. These compounds were then separated on polyethyleneimine-cellulose thin layers in ammonium formate and ammonium sulfate solutions. Autoradiograms of the chromatograms obtained by this high-resolution procedure showed the presence of nucleotides derived from chemically altered, as well as normal, DNA constituents. Maps from DNA exposed to any of the chemicals used exhibited a spot pattern typical for the particular chemical. This method detected a single adduct in 10(5) DNA nucleotides without requiring that the compound under investigation be radioactive and thus provides a useful test to screen chemicals for their capacity to damage DNA by covalent binding.

Animals↗
PubMed1982

Interferon inhibits Sendai virus-induced cell fusion: an effect on cell membrane fluidity.

Interferon can affect several cellular functions, in addition to its antiviral activity. We report here that pretreatment of human cells with homologous interferon significantly inhibits cell fusion induced by Sendai virus and that this refractory state is accompanied by a decrease in cell plasma membrane fluidity. Multinucleate cell formation induced by beta-propiolactone-inactivated Sendai virus in human fibroblast cells (a system in which fusion results from an interaction of the viral glycoprotein with the cell membrane) was inhibited by more than 90% after addition of human interferon for 18-24 hr. This inhibition could be neutralized by antiserum to interferon. Furthermore, inhibitor studies with cycloheximide and actinomycin D clearly indicated that synthesis of protein and RNA is necessary to establish the resistant state. To determine whether the inhibition of Sendai virus-induced cell fusion resulted from interferon-induced changes at the cell plasma membrane, experiments were carried out using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene, which is capable of sensing molecular motions in the hydrocarbon core of the bilayer structure. A significant decrease in the membrane fluidity of interferon-treated cells was observed. It is likely, therefore, that the inhibitory effect on Sendai virus-induced cell fusion observed in interferon-treated cells results from an increased rigidity of the target cell membrane.

Cell Fusion↗
PubMed1984

Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene.

Inoculation of rabbits and mice with a vaccinia-rabies glycoprotein recombinant (V-RG) virus resulted in rapid induction of high concentrations of rabies virus-neutralizing antibodies and protection from severe intracerebral challenge with several strains of rabies virus. Protection from virus challenge also was achieved against the rabies-related Duvenhage virus but not against the Mokola virus. Effective immunization by V-RG depended on the expression of a rabies glycoprotein that registered proline rather than leucine as the eighth amino acid from its NH2 terminus (V-RGpro8). A minimum dose required for effective immunization of mice was 10(4) plaque-forming units of V-RGpro8 virus. beta-propiolactone-inactivated preparations of V-RGpro8 virus also induced high levels of rabies virus-neutralizing antibody and protected mice against intracerebral challenge with street rabies virus. V-RGpro8 virus was highly effective in priming mice to generate a secondary rabies virus-specific cytotoxic T-lymphocyte response following culture of lymphocytes with either ERA or PM strains of rabies virus.

Animals↗