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Biomedical subjects

C A Bruggeman

Publications and source records attributed to C A Bruggeman.

At least 19 recordsLinked to original sources
PubMed1998

The Maastricht strain and England strain of rat cytomegalovirus represent different betaherpesvirus species rather than strains.

The major immediate early (MIE) locus of the Maastricht strain of rat cytomegalovirus (RCMV) was found to comprise five exons of which the first is noncoding. The first three exons are spliced to either exon 4, generating IE1, or exon 5, generating IE2. An additional splicing event unique to RCMV (Maastricht) was identified in exon 5, resulting in a 466-bp deletion. IE1 transcripts were detected exclusively during the IE phase of infection in vitro, whereas IE2 transcripts were detected during both the IE and late phase of infection. The similarities between amino acid sequences derived from the MIE gene of RCMV (Maastricht) and murine cytomegalovirus are low (22 and 37% for IE1 and IE2, respectively). Surprisingly, the similarities between the MIE proteins of RCMV (Maastricht) and the England strain of RCMV are also low (23 and 32% for IE1 and IE2, respectively). This suggests that these RCMV strains represent different betaherpesvirus species rather than strains. This is underscored by the difference between both viruses in genome size as well as growth characteristics. The existence of two different RCMV-like species might have important implications for the use of these viruses as models for human cytomegalovirus.

Animals↗
PubMed1998

Cytomegalovirus infection enhances the neointima formation in rat aortic allografts: effect of major histocompatibility complex class I and class II antigen differences.

BACKGROUND: The development of chronic rejection has emerged as a major cause of long-term graft failure. Previous studies have demonstrated that cytomegalovirus (CMV) infection is associated with an increased incidence of chronic allograft rejection in renal, cardiac, and aortic allografts. This study was designed to investigate the effects of the major histocompatibility complex (MHC) class I or class II mismatches on CMV-enhanced chronic rejection. METHODS: Aortic transplantation was performed between different inbred rat strain combinations; the Lewis to RP combination was class I-mismatched and Wag/Rij to RP class II-mismatched. At 7, 28, and 90 days after transplantation, the intensity of chronic rejection in mismatched grafts with or without CMV infection was evaluated using histological and immunohistological analysis. RESULTS: The results of this study demonstrated that CMV infection led to an increased influx of monocytes/ macrophages in class I-mismatched grafts at 1 week after transplantation and enhanced infiltration of T lymphocytes in class II-mismatched grafts at 4 weeks. Although more vascular lesions were observed in the class II-mismatched combinations, an intensified neointima formation by CMV infection was observed only in the MHC class I-mismatched allografts. CONCLUSIONS: CMV infection may increase neointima formation of allografts when an MHC class I disparity between donor and recipient is present. This may be associated with the increased perivascular influx of monocytes/macrophages observed in CMV-infected animals early after transplantation.

Animals↗
PubMed1998

Multiple organ involvement during experimental cytomegalovirus infection is associated with disseminated vascular pathology.

Since much of the pathogenesis of cytomegalovirus (CMV) disease is still unknown and vascular involvement may be of importance a rat model was used to study the nature and course of CMV-induced vascular pathology. In this model, local CMV infection was established by subcutaneous inoculation of rat-specific CMV (RCMV) in the sole of the foot. Sings of endothelial activation, including leucocyte adhesion, preceded detectable RCMV infection of these cells. ultimately, vasculitis and thrombotic occlusion were accompanied by diffuse tissue inflammation and necrosis. Generalized RCMV infection was induced in rats by intraperitoneal administration of the virus, which resulted in multiple organ pathology, including haemorrhages, inflammation, and gastrointestinal ulceration. RCMV-encoded antigens were found especially in mononuclear inflammatory cells in the organs and peripheral blood. In addition, multiple haemorrhages and disturbed haematological parameters indicated diffuse intravascular coagulopathy. In conclusion, this study provides evidence for extensive vascular involvement and haematological consequences during disseminated CMV infection. The nature and chronology of RCM-induced pathological vascular events were demonstrated, indicating the importance of endothelial damage. These data and further study may lead to a better understanding of the pathogenesis of CMV multiple-organ disease.

Animals↗
PubMed1998

Evaluation of a new method for early detection of active cytomegalovirus infections. A study in kidney transplant recipients.

Early detection of active cytomegalovirus (CMV) infection after organ transplantation is necessary to start effective antiviral treatment. In the present study, blood specimens of kidney transplant recipients (n = 38) were monitored for the expression of CMV immediate early (IE) and late (L) mRNA using nucleic acid sequence-based amplification (NASBA). Results were compared with virus isolation, pp65 antigenemia and serology. In patients developing active CMV infection, pp65 antigen and L mRNA were detected simultaneously. At the same time, positive cell culture results could be reported to the clinic. CMV was detected significantly earlier with IE NASBA than with the other assays. However, the specificity of IE NASBA is lower than that of antigenemia, late NASBA and cell culture. Early detection of IE mRNA is especially useful for patients at high risk of developing symptomatic CMV infection in order that early, adequate antiviral therapy may be started. Late NASBA can be used to monitor further development of CMV infection, comparable to antigenemia.

Cytomegalovirus Infections↗
PubMed1998

Nuclear import as a barrier to infection of human umbilical vein endothelial cells by human cytomegalovirus strain AD169.

Human embryonal fibroblasts (HEF) are fully permissive for infection by human cytomegalovirus (HCMV) strain AD169, whereas human umbilical vein endothelial cells (HUVEC) seem to form an almost complete barrier to infection with this virus. To investigate this difference in permissiveness, HCMV infection of both cell types was studied using in situ hybridisation (ISH) as well as immunocytochemistry to detect viral DNA and viral proteins. At 2 h post-infection (p.i.), viral DNA was detected dispersed throughout the cytoplasm in both HEF and HUVEC, indicating that HCMV enters all cells of both cell types. At 4 h p.i., the viral DNA was found in the nucleus in HEF, and at the same time expression of immediate early (IE) antigen was found. In contrast, in HUVEC the expression of the IE proteins occurred in a limited number of cells at 8 h p.i., while in most HUVEC an accumulation of viral DNA around the nuclei was observed at this time point. In HUVEC, the nuclear localisation of viral DNA was detected 16 h p.i. in a minority of cells, indicating that transport of HCMV DNA into the nucleus is considerably slower in HUVEC than in HEF. Furthermore, the number of HUVEC containing HCMV DNA decreased about six-fold between 8 and 48 h p.i., indicating that HCMV DNA is either transported into the nucleus or eliminated. Apparently, the lower permissiveness of HUVEC for the HCMV strain AD169 relative to HEF is due to inefficient transport of HCMV DNA into the nuclei of infected HUVEC.

Antigens, Viral↗
PubMed1998

Diagnostic value of monitoring human cytomegalovirus late pp67 mRNA expression in renal-allograft recipients by nucleic acid sequence-based amplification.

The diagnostic value of monitoring human cytomegalovirus (HCMV) late pp67 mRNA expression by nucleic acid sequence-based amplification (NASBA) after renal-allograft transplantation was evaluated. RNAs were isolated from 489 whole-blood specimens of 42 patients for the specific amplification of the late pp67 (UL65) mRNA. NASBA results were compared to results from the pp65 antigenemia assay, virus isolation by cell culture, and serology. The sensitivity value for NASBA proved to be higher than that for the antigenemia assay (50 versus 35%) for the detection of HCMV infection, while the sensitivity values of cell culture and NASBA were comparable (54 and 50%, respectively). NASBA detected the onset of HCMV infection simultaneously with cell culture and the antigenemia assay. Both the antigenemia assay and NASBA are very specific (100%) and highly predictive (100%) for the onset of HCMV infection. Antiviral therapy with ganciclovir resulted in negative results for cell culture, the antigenemia assay, and NASBA. In conclusion, monitoring HCMV pp67 mRNA expression by NASBA is a highly specific method for the detection of HCMV infection in renal-allograft recipients and is more sensitive than the antigenemia assay. Furthermore, NASBA can be used to monitor the progression of HCMV infections and the effect of antiviral therapy on viral activity.

Cytomegalovirus↗
PubMed1998

The R33 G protein-coupled receptor gene of rat cytomegalovirus plays an essential role in the pathogenesis of viral infection.

We have identified a rat cytomegalovirus (RCMV) gene that encodes a G-protein-coupled receptor (GCR) homolog. This gene (R33) belongs to a family that includes the human cytomegalovirus UL33 gene. R33 was found to be transcribed during the late phase of RCMV infection in rat embryo fibroblasts. Unlike the mRNAs from all the other members of the UL33 family that have been studied to date, the R33 mRNA is not spliced. To study the function of the R33 gene, we constructed an RCMV strain in which the R33 open reading frame is disrupted. The mutant strain (RCMV deltaR33) did not show differences in replication from wild-type RCMV upon infection of several rat cell types in vitro. However, marked differences were seen between the mutant and wild-type strain in the pathogenesis of infection in immunocompromised rats. First, the mutant strain induced a significantly lower mortality than the wild-type virus did. Second, in contrast to wild-type RCMV, the mutant strain did not efficiently replicate in the salivary gland epithelial cells of immunocompromised rats. Although viral DNA was detected in salivary glands of RCMV deltaR33-infected rats up to 14 days postinfection, it could not be detected at later time points. This indicates that although the strain with R33 deleted is probably transported to the salivary glands in a similar fashion to that for wild-type virus, the mutant virus is not able to either enter or replicate in salivary gland epithelial cells. We conclude that the RCMV R33 gene plays a vital role in the pathogenesis of infection.

Amino Acid Sequence↗
PubMed1997

Neointimal smooth muscle cell phenotype is important in its susceptibility to cytomegalovirus (CMV) infection: a study in rat.

OBJECTIVE: Recently, we have found that rat CMV (RCMV) infected smooth muscle cells (SMCs) in rat carotid arteries when administered 14 days after balloon injury. In the present study we investigated (1) the long term effects of CMV infection on neointimal cross-sectional area, and (2) whether the phenotype of the intimal SMCs influences their susceptibility to active CMV infection. METHODS: In the first part of the study, rats received RCMV intravenously, two weeks after balloon catheterisation of the left carotid artery and were sacrificed twenty weeks after catheterisation. Continuous BrdU infusion was performed by subcutaneously implanted osmotic pumps during the last two weeks of life. In the second part RCMV was administered eight weeks after catheterisation and rats were sacrificed two weeks later. Immunohistochemistry was used to detect viral antigens, to determine BrdU incorporation as well as the contents of alpha-actin, desmin and vimentin in the carotid arteries. Intima and media cross-sectional areas were determined using computerized morphometry. RESULTS AND CONCLUSIONS: RCMV infection did not induce any differences in intima or media cross-sectional areas of the injured carotid artery, nor in the extent of SMC proliferation as shown by BrdU incorporation, 20 weeks after balloon catheterisation. Eight weeks after balloon catheterisation, RCMV no longer infected neointimal SMCs. This non-responsiveness to RCMV was associated with "re-differentiation" of the eight weeks old neointima, compared with two weeks after catheterization, as shown by the contents of alpha-actin, desmin and vimentin. Our data suggest that intimal SMC phenotype determines its susceptibility to active RCMV infection in vivo. Since de-differentiation of neointimal SMCs is associated with enhanced proliferation of these cells it is stated that de-differentiation or proliferation is prerequisite for infection.

Analysis of Variance↗
PubMed1997

Effective treatment of experimental cytomegalovirus-induced encephalo-meningitis in immunocompromised rats with HPMPC.

Cytomegalovirus (CMV)-induced encephalomeningitis is a dramatic complication in patients with the acquired immunodeficiency syndrome (AIDS) and treatment of this infection remains a major clinical problem. In order to study the pathogenesis and treatment of CMV-induced encephalomeningitis, we experimentally induced intracranial rat CMV (RCMV) infection in rats that were immunosuppressed by total body X-irradiation. CMV infection was monitored by viral plaque assay for estimation of the viral load. CMV-induced pathology, the presence of CMV-infected cells, as well as the presence of T-lymphocytes and monocytes/macrophages were studied by histopathologic and immunohistochemical staining techniques. The meninges showed CMV infection in mononuclear infiltrative cells and in endothelium of small blood vessels 8 days after intracerebral inoculation. This was accompagnied by multiple haemorraghes and inflammatory cell infiltration. The infection and inflammatory response persisted for at least 21 days p.i. Animals were treated with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), hyperimmune serum (HIS) and both DHPG and HIS combined. Treatment with one dosage of HPMPC at 20 mg/kg effectively reduced virus titers. However, all other treatment modalities were not effective. In conclusion, the pathology of RCMV-induced encephalomeningitis in immunocompromised rats closely resembles that of AIDS patients. The infection is effectively treated by HPMPC.

Animals↗
PubMed1997

Intracellular thiol redox status affects rat cytomegalovirus infection of vascular cells.

There is increasing evidence for cytomegalovirus (CMV) induced vascular pathology during acute infection in the immunocompromised host. Inflammation is involved in such processes, which is frequently associated with increased levels of oxidative mediators and reduced anti-oxidant protection. A relation between viral infection and oxidative stress has been recognized for human immunodeficiency virus and herpes simplex virus-1 infections, but little is known in this respect for CMV infections. We investigated if there is a relation between CMV infection of vascular cells and the intracellular redox status using an in vitro rat model. We measured intracellular glutathione levels and rat CMV (RCMV) permissiveness of rat heart endothelial cell lines (RHEC), rat smooth muscle cells (RSMC), and compared these with fully CMV-permissive rat fibroblasts (REF and Rat 2). In addition, the effects of the anti-oxidant N-acetylcysteine (NAC) and the glutathione synthesis inhibitor buthionine sulfoximide (BSO) on CMV permissiveness and replication were investigated in these cell lines. Finally, we investigated infection of vascular cells under inflammatory conditions in an in vivo rat model for acute CMV infection. The results show a very high endogenous glutathione level in RHEC compared to REF, Rat 2 cells and RSMC. This is associated with a low CMV permissiveness in RHEC as opposed to full permissiveness in REF, Rat 2 cells and RSMC in vitro. In addition, modulation of the intracellular thiol redox status affected CMV infection and replication only in RHEC, but not in RSMC and Rat 2 cells. During acute infection in vivo under immunosuppressed conditions rat endothelial cells first become activated and subsequently infected leading to vascular damage and pathology. This study suggests that a high endogenous thiol redox status may contribute to the apparent barrier function of endothelial cells with respect of CMV infection and that oxidative stress may facilitate CMV infection of the vascular wall.

Acute Disease↗
PubMed1997

Activation of protein kinase C enhances the infection of endothelial cells by human cytomegalovirus.

The infection of cultured endothelial cells with human cytomegalovirus (HCMV) is generally limited to less than 10% of the cells in contrast to HCMV infection of fibroblasts, where essentially all cells can be infected. It is known that HCMV infection influences a number of signal transduction pathways of infected cells. We therefore questioned whether, conversely, the infectivity of human umbilical vein endothelial cells could be influenced by the deliberate activation of these pathways. When endothelial cells were treated prior to infection with phorbol myristoyl acetate, an activator of protein kinase C, the number of HCMV-positive cells increased two to three times. On the other hand, pretreatment of the cells with RO 31-8220, a specific protein kinase C inhibitor, or with staurosporine, a general protein kinase inhibitor, resulted in a decreased infection level and in abolishment of the PMA-induced effect. Pretreatment with the protein phosphatase inhibitor, okadaic acid, caused a slight increase in infectivity, whereas pretreatment with the protein tyrosine kinase inhibitor, genistein, was without effect. Furthermore, neither forskolin and ilomedine, compounds known to activate the endothelial adenylate cyclase, nor the calcium ionophore A23187 were able to influence HCMV infectivity. It is concluded that: (a) the HCMV infection level of unstimulated endothelial cells is influenced by the basal level of protein kinase C; and (b) stimulation of protein kinase C prior to infection results in an increase of infection by HCMV.

Calcimycin↗
PubMed1997

Infection with rat cytomegalovirus (CMV) in the immunocompromised host is associated with the appearance of a T cell population with reduced CD8 and T cell receptor (TCR) expression.

Infection with human cytomegalovirus (HCMV) mostly results in a chronic subclinical infection; the immune system is unable to eliminate the virus and is apparently in equilibrium with the persistent virus. In the immunosuppressed host this equilibrium is disturbed, resulting in clinical infection. Rat cytomegalovirus (RCMV) infection in its host can be used as a model for HCMV infection. Using flow cytometry we examined the effect of acute RCMV infection on the composition of leucocyte subsets in the peripheral blood of both immunocompetent and immunosuppressed (5 Gy total body irradiation) Lewis rats. Special attention was paid to the natural killer (NK) cells and the CD8+ T cells known to be involved in the control of viral infections. Furthermore, we determined the presence of leucocyte subsets in the internal organs by immunohistochemistry. In immunocompetent rats, infection caused a small increase in NK cells and a large increase in CD8+ T cells. In contrast, infection of immunosuppressed rats caused a marked increase in NK cells and a small increase in CD8+ T cells, consisting of T cells with reduced expression of both CD8 and TCR. This phenomenon is characteristic of anergic CD8+ T cells, possibly explaining the ability of the virus to escape elimination by the immune system. The increase of NK cells in the peripheral blood of immunosuppressed, RCMV-infected rats could also be detected in kidney, liver, lung and pancreas, but not in salivary gland. This could explain the long persistence of infectious virus in the salivary gland.

Animals↗
PubMed1997

Cloning and functional characterization of the origin of lytic-phase DNA replication of rat cytomegalovirus.

A cis-acting sequence within the rat cytomegalovirus (RCMV) genome (oriLyt) that directs initiation of lytic-phase DNA replication is identified in this report. RCMV oriLyt was localized within a 4.3 kb NcoI fragment that is situated immediately upstream of the gene encoding the major DNA-binding protein. The activity of oriLyt was investigated in a transient replication assay, in which the ability of plasmid constructs to promote DNA replication was tested. Replication of oriLyt-containing plasmids was autonomous and resulted in the generation of high-molecular-mass concatemers of head-to-tail-linked plasmid oligomers. oriLyt-mediated replication was found to depend on viral DNA polymerase activity supplied by RCMV infection. The sequence required for oriLyt function was found to reside within a 3.3 kb HincII-NcoI fragment. The RCMV oriLyt sequence is highly complex, containing 23 direct repeats (DRs) and 16 inverted repeats (IRs) of lengths greater than 10 bp. Two of the DRs (DR21 and DR22) are exceptionally large, being 80 and 88 bp in length, respectively. In addition, two sequence elements (of 127 and 120 bp) with dyad symmetry were identified within oriLyt. Although the sequence similarity of RCMV oriLyt with its human cytomegalovirus counterpart is limited, there is a striking resemblance in the overall organization of several IRs and DRs within both sequences.

Animals↗
PubMed1997

Widespread presence of cytomegalovirus DNA in tissues of healthy trauma victims.

AIMS: To determine the localisation of human cytomegalovirus (CMV) DNA in abdominal aorta, spleen, and transplantable organs, such as kidney, pancreas, and liver, obtained from healthy individuals; to characterise the cell type(s) in these tissues that serve as a reservoir for latent CMV. METHODS: CMV DNA was detected by dot blot DNA hybridisation and in situ DNA hybridisation with a probe for CMV major immediate early sequences (UL123) and nested PCR with primers derived from the CMV major immediate early (IE) gene exon 4 (UL123ex4). Samples of liver, abdominal aorta, spleen, kidney, and pancreas were obtained at necropsy or from donor kidneys from healthy subjects. RESULTS: CMV DNA was detected in most tissue samples using dot blot hybridisation and nested PCR. In situ hybridisation demonstrated that, in addition to smooth muscle cells in the arterial wall, hepatocytes, tubular and glomerular kidney cells, splenic red pulp cells, and pancreatic acinar cells also harboured CMV DNA. CMV DNA was detected in seropositive and in some seronegative subjects. CONCLUSION: CMV DNA is widely distributed in organs of healthy subjects. CMV DNA was found in various cell types in several organs, suggesting that during latency, CMV DNA is present thoughout the body.

Adolescent↗
PubMed1997

Cytomegalovirus infection enhances experimental obliterative bronchiolitis in rat tracheal allografts.

Inbred DA (AG-B4, RT1a) and WF (AG-B2, RT1v) rat immunosuppressed with cyclosporine A (CsA) 2 mg/kg/day subcutaneously were used as donors and recipients of heterotopic rat tracheal allografts. Acute infection was established by inoculating the recipients with 10(5) plaque-forming units of rat cytomegalovirus (RCMV) intraperitoneal on the day of transplantation. Chronic RCMV infection was similarly established 8 wk before transplantation in donors alone, recipients alone, and in both donor and recipients. The control rats were left noninfected. For in vivo cell proliferation, the rats received bromedeoxyuridine intravenously 3 h before being killed. RCMV infection significantly enhanced the generation of experimental obliterative bronchiolitis (OB). First, acute RCMV infection was linked to markedly enhanced MHC class II expression on the respiratory epithelium and prominent airway wall inflammation of W3/25+ T cells (CD4+) and ED1+/ED2+ macrophages. Second, acute infection induced a fivefold increase in luminal occlusion of the trachea, due to proliferating inflammatory and alpha-smooth muscle actin+ myofibroblast-like cells. Acute RCMV infection was particularly associated with markedly increased expression of platelet-derived growth factor (PDGF) AA-isoform in various structures of the graft 10 d after transplantation. At 30 d, RCMV significantly increased PDGF alpha- and beta-receptor expression in alpha-smooth muscle actin+ cells and TNF-alpha expression in capillary endothelial cells of the fibroproliferative lesion. In chronic recipient RCMV infection, the histopathological changes were quite similar to acute infection. Chronic donor infection did not amplify the development of experimental OB. As analyzed by immunohistochemistry from the grafts and by plaque assays from salivary gland biopsies of the recipients, trace RCMV antigen expression, while no infectious RCMV could be recovered in the chronic donor infection group. In other infected groups, RCMV antigen expression was mild to moderate and salivary glands contained plenty of infectious RCMV. To conclude, our results indicate that RCMV infection enhances epithelial MHC class II expression and myofibroproliferation in heterotopic rat tracheal allografts and suggest that these changes may be induced by increased PDGF-AA and PDGF alpha-receptor expression, respectively.

Acute Disease↗
PubMed1996

Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat.

A possible mechanism of the induction of lung transplant rejection by cytomegalovirus (CMV) infection is the inflammatory upregulation of adhesion ligand molecules on transplant endothelia by the viral infection leading to leukocyte activation. To study this question a rat model of rat cytomegalovirus (RCMV) infection and acute lung transplant rejection was established to study: (1) the influence of RCMV infection on the course of rejection, (2) the influence of rejection on the course of RCMV infection, and (3) the influence of RCMV on adhesion molecule expression and leukocyte infiltration. For this Lew (RT1l) rats received either syngenic (n=25) or allogeneic (BN, RT1n; n=38) left lateral lung transplants. Postoperatively, CsA 25mg/kg was given on days 1-3 and triple drug (CsA, Aza, Pred) immunosuppression was given from days 4-10 to induce systemic RCMV infection and acute rejection developed from postoperative day (POD) 15-25 in allogeneic transplants. In RCMV-positive animals the rejection grade was gradually increased at POD 15 and 18. Furthermore, after allogeneic transplantation an enhanced viral infection of the lung transplant as early as POD 11 was found and increased salivary gland PFU titers on days 20 and 25. In the absence of rejection infiltration a maximal induction of ICAM-1 adhesion molecules was found on lung endothelia in RCMV+ allogeneic animals as compared with noninfected controls. This induction was found to lesser degree for VCAM-1 and MHC class II adhesion ligand molecules. This was accompanied by a significantly increased CD11a+ and CD49d+ leukocyte infiltration into the alveolar interstitium on day 11 and 15 in infected transplants. The results show an enhancement of RCMV infection after allogeneic lung transplantation leading to endothelial activation and recruitment of CD11a/CD49d+ leukocytes. This mechanism may strongly influence transplant inflammation and the long-term course of lung transplant rejection.

Animals↗
PubMed1996

IgM antibody detection of ppUL80A and ppUL32 by immunoblotting: an early parameter for recurrent cytomegalovirus infection in renal transplant recipients.

The value of IgM detection for the early diagnosis of an active cytomegalovirus (CMV) infection in renal transplant recipients was evaluated prospectively. Sequential serum samples obtained from 22 allograft recipients with active CMV infection were tested for the presence of CMV-specific immunoglobulin M antibodies (IgM) by an enzyme-linked immunosorbent assay (ELISA) and a microparticle enzyme immunoassay (MEIA) and were compared with the Western-immunoblotting technique (IB). The time course of CMV IgM antibody detection was evaluated in relation to the shell vial assay (SVA), CMV disease, and immunosuppressive regimen. By IB, IgM antibodies against the capsid protein ppUL80a and the basic matrix phosphoprotein ppUL32 were detected in all 22 recipients with active CMV infection. Using the MEIA and the ELISA, the presence of CMV IgM antibodies was detected in 17 (77%) and ten (46%) of these 22 recipients, respectively. The SVA was the earliest parameter for detection of primary CMV infection in seven of nine (78%) recipients, in contrast to two of 13 (15%) patients with recurrent CMV infection (P < .05). The detection of IgM antibodies by IB was the earliest parameter for detection of recurrent CMV infection in seven out of 13 (54%) recipients in contrast to one out of nine (11%) patients with primary CMV infection (P < .05). During a primary CMV infection, the development of an abundant IgM antibody response was associated with recovery from CMV disease and the end of the viremic phase.

Antibodies, Viral↗