Cytomegalovirus Infections Following Renal Transplantation

The envelope glycoprotein B of human cytomegalovirus (CMV) is a major target of the neutralizing antibody response against this virus, and hence has importance as a potential subunit vaccine. PCR was utilized to amplify DNA encoding the dominant antigenic determinant on this molecule, AD-1 (codons 552 to 635), and DNA sequencing was carded out in order to compare nucleotide variation in AD-1 between clinical isolates of CMV and the laboratory strain AD169. Wild-type CMV strains isolated from AIDS patients were not only more likely to possess nucleotide substitutions (19/24 compared to 5/25, P< 0.0001) than those from renal transplant recipients, but they also exhibited a greater degree of nucleotide sequence divergence (6.94 versus 0.82 substitutions/1000 bp, P < 0.0001; 96.0 to 100% versus 99.4 to 100% similarity). Increased sequence variation in the AIDS patients did not correlate with absolute peripheral blood CD4 ÷ T cell level (r = 0"33, P > 0"1). Only two strains from AIDS patients and one strain from the renal transplant recipients possessed nucleic acid substitutions that resulted in codon changes, indicating that AD-1 is relatively well conserved amongst clinical isolates of CMV. The demonstration of strains with codon changes within neutralizing epitopes, however, highlights the importance of taking into consideration the presence of these strains within the wildtype virus population when preparing subunit vaccines.

mentioning

confidence: 99%

Sequence variation within neutralizing epitopes of the envelope glycoprotein B of human cytomegalovirus: comparison of isolates from renal transplant recipients and AIDS patients

Roy

Grundy²,

Emery³

1993

“…However, HCMV is a significant cause of morbidity and mortality in infants infected in utero and in immunocompromised hosts (Weller, 1971;Glenn, 1981).…”

mentioning

confidence: 99%

Murine cytotoxic T cell response specific for human cytomegalovirus glycoprotein B (gB) induced by adenovirus and vaccinia virus recombinants expressing gB

Berencsi

Rando

deTaisne

et al. 1993

A murine model of the cytotoxic T lymphocyte (CTL) response to glycoprotein B (gB) of human cytomegalovirus (HCMV) was developed based on the use of adenovirus (Ad) and vaccinia virus (Vac) recombinants expressing gB. Mice of different major histocompatibility haplotypes [CBA (H-2k), BALB/k (H-2 k) and BALB/c (H-2d)] infected with the Ad-gB recombinant developed an Ad-specific CTL response. However, only the H-2 k mice developed a significant HCMV gBspecific CTL response, as indicated by the major histocompatibility complex class I-restricted lysis of Vac strain Copenhagen (VacC)-gB recombinant-infected target cells by H-2 k mouse immune spleen cells. The VacC-gB recombinant elicited only a weak gB-specific CTL response in these mice, indicating that the observed gB-specific CTL response in mice is dependent on the expression vector used for immunization. The gBspecific cytotoxicity observed in H-2 k mice was mediated by the CD8 lymphocyte subset.

“…Human cytomegalovirus (HCMV) is a major pathogen (Weller, 1981;Glenn, 1981;Griffiths, 1987) which currently is poorly managed by chemotherapy using e.g. gancyclovir (Field et al, 1983;Freitas et al, 1985).…”

mentioning

confidence: 99%

High level expression of DNA polymerases from herpesviruses

Ertl

Thomas²,

Powell³

1991

The DNA polymerase genes of human cytomegalovirus (HCMV) and varicella-zoster virus (VZV) were inserted separately into the polyhedrin gene of Autographa ealifornica nuclear polyhedrosis virus (AcNPV) by cotransfection of Spodoptera frugiperda (SFg) cells with baculovirus transfer vectors carrying the genes and AcNPV infectious DNA. Infection of SF9 cells with the recombinant viruses resulted in expression from the polyhedrin promoter of proteins of the expected Mrs. These proteins possessed DNA polymerase activities similar to that of the enzymes induced by the respective herpesvirus in infected cells, and were identified as HCMV and VZV DNA polymerase using inhibitors and specific antisera reactive with each enzyme.