PubMed Health⌕ Search

Biomedical subjects

A R Neurath

Publications and source records attributed to A R Neurath.

148 records · Page 9Linked to original sources
PubMedDate not supplied

Translational selection in the expression of the hepatitis B virus envelope proteins.

The region of the hepatitis B virus (HBV) genome coding for the viral envelope proteins contains three inphase ATGs that are conserved among viral subtypes. Each of these ATGs can be used as mRNA initiation codons. The three translated proteins share a carboxy-terminal region (the S protein) and extend amino-terminally to include the pre-S2 region in the middle (M) protein, and the pre-S1 and pre-S2 regions in the large (L) protein. We have inserted the HBV DNA coding for the M protein into a baculovirus expression vector. Infected insect cells transcribe a mRNA that is initiated solely within a baculovirus promoter, and that contains the initiator codons for both M and S proteins. Although these cells primarily secrete the M protein, the major translational product is the S protein, which is not secreted. This preferential translation, the result of the use of an internal initiator codon, demonstrates that the regulation of HBV envelope protein production can occur at the translational level.

Cloning, Molecular↗
PubMedDate not supplied

Toleration of amino acid substitutions within hepatitis B virus envelope protein epitopes established by peptide replacement set analysis. II. Region S(122-136).

The envelope of the hepatitis B virus (HBV) consists of three related proteins, designated S-, M- and L-protein, all of which share a common 226-amino acid residue sequence, corresponding to the S-protein that is sufficient for eliciting protective immunity against HBV. HBV variants, resulting from point mutations leading to replacements of amino acids within the S(122-160) segment of S-protein, have been recently recognized. In order to assure the continued success of vaccination against HBV and the adequacy of diagnostic tests for HBV envelope antigens and antibodies, it is necessary to understand the impact of amino acid replacements on the immunological recognition of S-protein at both the B- and T-cell levels. Immunologically tolerated and forbidden amino acid replacements within the S(139-147) segment of S-protein have already been discerned. The impact of amino acid substitutions within the S(122-136) segment on the immunological recognition of S-protein is analyzed in this report. Such replacements do not appreciably affect the binding of rabbit and goat anti-S antibodies to replacement set peptides, while decreased murine antibody binding was observed with some peptides having substitutions at residues 122, 123 and 133. On the other hand, amino acid substitutions within the (126-136) region, except those distinguishing serological subtypes of HBV from each other, abrogated murine T-cell proliferative responses to the peptides, while substitutions at residues 122, 123 and 125 had a lesser effect. Some of the peptides with amino acid substitutions peculiar to the variants had diminished stimulatory activity for T-cells from individuals vaccinated against hepatitis B. Amino acid substitutions in both the S(139-147) and S(122-136) segments of S-protein may potentially result in variant viruses escaping immunological surveillance based on current hepatitis B vaccines.

Amino Acid Sequence↗
PubMedDate not supplied

Toleration of amino acid substitutions within hepatitis B virus envelope protein epitopes established by peptide replacement set analysis. I. Region S(139-147).

B and T cell epitopes expressed on the surface of S-protein, a major constituent of the envelope of hepatitis B virus (HBV), are essential for eliciting protective immunity against HBV infection. A segment of the S-protein sequence encompassing residues S(139-147) is a portion of overlapping B and T cell epitopes. This sequence is conserved among distinct serological subtypes of HBV and has a 77.8% homology with an analogous sequence in S-proteins of nonhuman mammalian hepadnaviruses. Rare subtypes and variants of HBV having amino acid replacements within the S(139-147) sequence were discerned recently. The impact of amino acid replacements within this sequence on its immunological recognition at both the B and T cell levels was explored by peptide replacement set analysis. Results of the analysis permit discrimination between tolerated and forbidden amino acid replacements and provide a background for the development of reagents and immunogens specific for emerging HBV variants.

Amino Acid Sequence↗