Glycoprotein gpll6 of human cytomegalovirus (HCMV) is a target for neutralizing antibodies. Gp 116 is a component of the gCI complex which consists of gp58 and gp116. Like its homologue, glycoprotein B of herpes simplex virus type 1, gp116 contains a highly antigenic region in the N-terminal part of the molecule, between amino acids 28 and 84. Prokaryotic expression plasmids and synthetic peptides were used to define binding sites for mouse and human monoclonal antibodies (MAbs) as well as HCMV convalescent sera. Site I, located between amino acids 68 and 77, contains an epitope recognized by the human MAb C23, which is capable of neutralizing HCMV independently of complement and the site is conserved between HCMV strains. Of HCMV-positive human sera, 53% recognized site I. Site II was mapped using mouse MAbs as well as human sera. It is located between residues 50 and 54, an area which is not conserved between strains AD169 and Towne, the two laboratory strains of known sequence. Strain-specific antibodies were detected in 25% of human sera. Site lI-specific antibodies, purified from human sera by affinity chromatography, were found to be incapable of neutralizing HCMV in tissue culture.
The frequencies of reactivated disease due to varicella-zoster virus (VZV) in immunocompromised patients were determined by enzyme-linked immunosorbent assay for antibody and also by the lymphocyte proliferation response to VZV antigen. Subclinical reactivations were as common as classical herpes zoster in all patient groups. Among bone marrow transplant (BMT) recipients, 36% developed herpes zoster and 26%, a subclinical reactivation. The corresponding frequencies for patients with leukemia during induction therapy were 5% and 10%; in renal transplant recipients, 0% and 26%; and in patients with seminoma, 0% and 6%, respectively. Subclinical reactivation of VZV thus appears to be a common finding in severely immunocompromised patients. A regained lymphocyte proliferation response to VZV antigen is a sensitive indicator of subclinical reactivation of VZV in BMT recipients. None of 19 BMT recipients with subclinical disease due to VZV later developed clinical reactivation of VZV. Acyclovir given as prophylaxis against infection with herpes simplex virus reduced the number of clinical and subclinical reactivations of VZV during treatment in BMT recipients, but not thereafter.
The humoral immune response to human cytomegalovirus (CMV) membrane glycoprotein gp58/116 (gB) has been studied by establishing cell lines producing specific human monoclonal antibodies. These cell lines were generated from peripheral blood lymphocytes obtained from a healthy carrier. Hybridomas producing gp58/116-specific antibodies were detected by reactivity to procaryotically expressed proteins containing the major neutralizing epitopes of this glycoprotein complex. One antibody, ITC88, which recognized an epitope located between amino acid residues 67 and 86 of gpll6, potently neutralized the virus at 1 to 2 tLg of immunoglobulin G per ml. Only four of the six human antibodies detecting the major neutralizing domain of gp58 neutralized the virus, and none of them required complement for activity. All antibodies that bound mature, processed gp58 recognized a conformational epitope involving sequences between residues 549 and 635. However, small differences existed between the antibodies in the actual minimal requirement for Cand N-terminal parts of this epitope. By peptide mapping with several of the antibodies, the epitope was shown to
Recent reports have focused interest on human cytomegalovirus (HCMV) in inflammatory bowel diseases (IBD). Our aim in this study was to examine the frequency of HCMV-infected intestinal cells in tissue sections obtained from patients with IBD, and to investigate if HCMV-infected intestinal cells produce the proinflammatory cytokine IL-6. We studied intestinal tissue sections from 13 patients with ulcerative colitis, 10 with Crohn's disease, 10 cancer patients without intestinal inflammation, and 10 samples from HCMV-infected AIDS patients. HCMV-DNA was detected by in situ hybridization in sections obtained from 12/13 patients with ulcerative colitis, in 10 with Crohn's disease, in 10/10 samples from HCMV-infected AIDS patients, but not in any of the 10 samples that were obtained from uninflamed tissues. HCMV-specific antigens were detected in samples from all HCMV-infected AIDS patients, in 11/13 sections from patients with ulcerative colitis, in 10/10 samples from patients with Crohn's disease, but not in sections from uninflamed tissues. Cells were double positive for an HCMV early antigen and IL-6 in 10/13 sections from patients with ulcerative colitis, in all patients with Crohn's disease, and in 4/10 samples from AIDS patients. In conclusion, these results suggest that active HCMV infection in the intestine is very frequent in patients with IBD, and may contribute to the inflammatory process through an increased production of IL-6.
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