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Biomedical subjects

A R Neurath

Publications and source records attributed to A R Neurath.

At least 145 records · Page 8Linked to original sources
PubMed1966

Density gradient centrifugation studies on rabies virus.

Neurath, A. Robert (The Wistar Institute, Philadelphia, Pa.), Tadeusz J. Wiktor, and Hilary Koprowski. Density gradient centrifugation studies on rabies virus. J. Bacteriol. 92:102-106. 1966.-Cesium chloride density gradient centrifugation of rabies virus revealed a heterogeneous population of infectious virus particles, the majority of which showed a density of 1.20 g/ml. From results obtained by rate zonal centrifugation in preformed sucrose gradients, it was possible to calculate a sedimentation coefficient of about 600S for rabies virus. Sedimentation coefficients of about 23S and 10S were calculated for two soluble rabies antigens present in infected tissue-culture fluids, and they showed a density of 1.26 g/ml in cesium chloride solutions.

Antigens↗
PubMedDate not supplied

Blocking of CD4 cell receptors for the human immunodeficiency virus type 1 (HIV-1) by chemically modified bovine milk proteins: potential for AIDS prophylaxis.

The chemical transformation of synthetic combinatorial libraries to increase the diversity of compounds of medicinal interest was reported recently. Chemical modification of natural products represents a complementary approach to accomplish this aim. Modification of lysines by aromatic acid anhydrides, preferentially by 3-hydroxyphthalic and trimellitic anhydrides and trimellitic anhydride chloride, converted commonly available proteins (human and bovine serum albumin and casein) into potent inhibitors of (i) binding between the HIV-1 gp 120 envelope glycoprotein and the CD4 cell receptor, probably owing to their binding to CD4, and (ii) infection by HIV-1. Modified bovine milk proteins are also potent HIV-1 inhibitors and may have potential for anti-HIV-1 prophylaxis.

Anhydrides↗
PubMedDate not supplied

Structural requirements for and consequences of an antiviral porphyrin binding to the V3 loop of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp120.

Several porphyrin derivatives were reported to have anti-HIV-1 activity. Among them, meso-teta(4-carboxyphenyl)porphine (MTCPP) and other carboxyphenyl derivatives were the most potent inhibitors (EC50 <0.7 mu M). MTCPP bound to the HIV-1 envelope glycoprotein gp120 and to full-length V3 loop peptides corresponding to several HIV-1 isolates but not to other peptides from gp120 + gp41. However, it remained possible that MTCPP bound to regions on gp120 which cannot be mimicked by peptides. Further characterization of the binding domain for MTCPP is important for understanding the antiviral activity of porphyrins and for the design of anti-HIV-1 drugs interfering with functions of the virus envelope. Results presented here show that: (i) deletion of the V3 loop from the gp120 sequence resulted in drastically diminished MTCPP binding, suggesting that the V3 loop is the dominant if not the only target site on gp120; (ii) this site was only partially mimicked by full-length V3 loop peptides; (iii) MTCPP binding to the gp120 V3 loop elicited allosteric effects resulting in decreased accessibility of the CD4 receptor binding site; (iv) the binding site for MTCPP lies within the central portion of the V3 loop (KSIHIGPGRAFY for the HIV-1 subtype B consensus sequence) and does not involve directly the GPG apex of the loop. These results may help in designing antiviral compounds with improved activity.

Allosteric Regulation↗
PubMedDate not supplied

Inhibitory activity of monoclonal antibody F35.25 on the interaction between hepatocytes (HepG2 cells) and preS1-specific ligands.

The capacity of a preS1-specific monoclonal antibody (McAb) F35.25 to block the attachment of preS1-specific ligands to human hepatoma HepG2 cells was studied. In order to define more precisely the fine epitope specificity of McAb F35.25, its reaction with synthetic peptides derived from the preS1 sequence (12-53) was investigated. McAb F35.25 was found to recognize better synthetic peptide preS(21-47) from the adw 2 and ayw sequences than the synthetic peptide preS(32-53) adw 2. The shortest sequence recognized by McAb F35.25 among the peptide sequence studied was preS(32-47). The corresponding amino acid sequence (for HBV subtype adw 2) is PAFGANSNNPDWDFNP. As expected, it was found that McAb F35.25 inhibited the attachment of HepG2 cells to HBsAg-cellulose, as well as to preS(21-47)-cellulose, corresponding to two HBV subtypes adw 2 and ayw. Finally, the inhibitory effect of different peptides on the interaction of McAb F35.25 with HBsAg particles containing the preS1 sequence was also studied. The peptide preS(12-47) appeared to be the most effective inhibitor. Therefore, the McAb F35.25 is specific for the sequence preS1(X to 47), where (12 less than or equal to X less than 32). These results indicate that McAb F35.25 is probably virus-neutralizing and represents a reagent of great value to study the interaction between HBV and hepatocytes independently of d/y subtype changes.

Amino Acid Sequence↗
PubMedDate not supplied

Delineation of contiguous determinants essential for biological functions of the pre-S sequence of the hepatitis B virus envelope protein: its antigenicity, immunogenicity and cell-receptor recognition.

The preS region of the hepatitis B virus (HBV) envelope protein has the following properties: (1) exposure on the surface of the virus; (2) high immunogenicity; (3) involvement in the reaction of the virus with cell receptors and (4) elicitation of antibodies protective against infection. Attempts to mimic B- and T-cell epitopes on the native protein by synthetic peptides were highly successful. This success depended on identification of those regions within the preS sequences which are the most important for biological function of the virus and for immunity, and on the synthesis of long peptides (20-40 residues) containing both B- and T-cell epitopes. Results presented here highlight those subregions of the preS sequence which are the most essential for the antigenicity and immunogenicity of HBV.

Amino Acid Sequence↗
PubMedDate not supplied

Hepatitis B virus contains pre-S gene-encoded domains.

One of the open reading frames on hepatitis B virus (HBV) DNA comprises the coding region (designated the env gene) for the virus envelope proteins. Studies on messenger RNA transcription suggest that this gene has the potential to code for three related proteins: (1) a protein of 226 amino acids identified as a major protein constituent of the HBV envelope, termed S-protein; (2) a protein with 55 additional amino acids at the N-terminal coded for by a portion of the env gene upstream of the S-gene (pre-S); (3) a protein corresponding to the entire env gene (pre-S + S). Synthetic peptides from the N-terminals of proteins (2) and (3), and antisera to them have been used to study the occurrence and properties of pre-S sequences. The results presented here provide unambiguous evidence that all three env encoded proteins are present in HBV particles; synthetic peptides corresponding to the gene encoding pre-S are highly immunogenic and can be used in diagnostic tests for detection in human sera of antibodies preferentially recognizing HBV; such antibodies, specific for pre-S determinants, are elicited during hepatitis B infection and by immunization with HBV proteins (2) and (3); the hepatitis B vaccine licensed in the United States does not contain pre-S proteins; and the pre-S proteins of the HBV envelope contain domains specifically recognized by liver cells. These findings suggest that pre-S determinants are important in virus-neutralizing responses and should be present in HBV vaccines.

Antibody Specificity↗