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Biomedical subjects

J Crompton

Publications and source records attributed to J Crompton.

4 recordsLinked to original sources

Expression of a foreign epitope on the surface of the adenovirus hexon.

To present short protein sequences to the host immune system a foreign epitope has been expressed on the surface of the adenovirus virion as part of the hexon. As the trimeric hexon constitutes 240 out of the 252 capsomers of the virus, the foreign epitope is repeated 720 times on the virion surface. An eight amino acid sequence from the major antigenic site in the VP1 capsid protein of poliovirus type 3 was engineered into two regions of the adenovirus type 2 hexon. The two loop regions chosen to accommodate the foreign sequences are exposed on the surface of the virion, show sequence variation between serotypes and are the sites of interaction with neutralizing antibodies. Virus with substitutions in loop I had wild-type growth characteristics, whereas virus with substitutions in loop II grew poorly. Adenoviruses with poliovirus sequences in loop I were recognized and efficiently neutralized by antisera specific for the poliovirus sequence; an antiserum raised against the adenovirus with the poliovirus insert specifically recognized the VP1 capsid protein of poliovirus type 3. It is therefore feasible to alter the surface properties of the adenovirus virion and in doing so to manipulate the immune response to this virus.

Adenoviruses, Human

Antipeptide antisera define neutralizing epitopes on the adenovirus hexon.

The adenovirus (Ad) hexon contains both group-and type-specific antigenic determinants. To identify the latter, peptides were synthesized corresponding to residues 281 to 292 from loop 1 and 441 to 455 from loop 2 of the Ad2 hexon. These sequences display type-specific variation and have been shown by X-ray crystallography to be present on the surface of the virion. Antisera raised against the peptides bound both peptide and the native hexon in ELISA, and blocked virus infectivity, as determined by immunofluorescence or neutralization assays. The loop 1 peptide was shown to inhibit binding of the corresponding antiserum to the native hexon in ELISA and to abolish its neutralizing activity. Neither the loop 1- nor loop 2-specific antiserum neutralized the infectivity of Ad4 or Ad40. Neutralization did not appear to result from aggregation of virus particles and thus their inability to attach to the cell, because virions treated with immune serum were internalized to the same extent as those treated with preimmune serum. Examination of the immune response elicited by Ad2 infection revealed that antibodies directed against the L1 and L2 epitopes were also present in human serum. Thus, the variable regions exposed on the surface of the Ad2 hexon represent type-specific neutralizing antigenic determinants.

Adenovirus Infections, Human

Congenital blindness, porencephaly, and neonatal thrombocytopenia: a report of four cases.

Four unrelated infants with neonatal thrombocytopenia associated with congenital blindness and porencephaly have been seen over an 18-year period. The association of congenital blindness with neonatal thrombocytopenia has not previously been reported. All children had clinical purpura in the neonatal period; in three cases, thrombocytopenia was confirmed, while in one case, the diagnosis of thrombocytopenia was presumptive; in two cases, there was evidence of circulating maternal serum platelet isoantibodies. Extensive investigation for intrauterine infection was negative in the three cases with confirmed thrombocytopenia. The thrombocytopenia resolved spontaneously after the neonatal period. It is postulated that the porencephalies were the consequence of prenatal cerebrovascular episodes. The etiology of the optic atrophy is unclear. Serial cranial ultrasound investigation is recommended for all neonates with thrombocytopenia, even if neurologically asymptomatic in the neonatal period, and serial prenatal cranial ultrasound investigation is recommended for infants of mothers with a history of having previously had infants with neonatal isoimmune thrombocytopenia.

Adolescent

Persistent pupillary membranes.

Extensive persistent pupillary membranes which occlude the pupil may occur in isolation or in association with other ocular anomalies. Amblyopia may result if the membranes are extensive. We favor nonsurgical intervention except if unusual circumstances are present as demonstrated in one of our two cases.

Child