A comparative study of congenital and postnatally acquired human cytomegalovirus infection in infants: lack of expression of viral immediate early protein in congenital cases

Abstract

Postmortem tissues from infants with congenital and postnatally acquired human cytomegalovirus (HCMV) infection were examined by routine histology, immunohistochemistry (IHC) and in situ hybridization (ISH) to determine the dynamics of viral replication in vivo. Histologically, infants in both groups showed characteristic inclusion-bearing cells most commonly in lung, kidney, liver and pancreas. IHC for late proteins using a rabbit polyclonal antibody and ISH for viral genomes detected most of the infected cells as nuclear and/or cytoplasmic signals. However, immunostaining with a monoclonal antibody against viral immediate early (IE) proteins was variable depending on the stage of viral replication within an individual infected cell. In tissues of infants with postnatal HCMV infection, many cells harboured IE antigens, while in tissues from congenital cases most of the affected cells lacked IE antigens and only a few showed cytoplasmic staining. The difference was not caused by the antigenic diversity among viral strains as confirmed by in vitro study. Our findings suggested that congenital infections exhibited uniformly late stage proteins with inactive viral replication at death, while acquired ones remained active. The different viral activity may reflect the immune status of congenital and acquired HCMV infections.

Human cytomegalovirus as a direct pathogen: Correlation of multiorgan involvement and cell distribution with clinical and pathological findings in a case of congenital inclusion disease

“…It was assumed that there is no active viral replication in fatal congenital inclusion disease at death and that indirect pathogenetic mechanisms are responsible for the clinical manifestations of congenital inclusion disease. This was concluded from the finding that no HCMV immediate early antigens could be detected in autopsy tissues using ''home-made'' antibodies generated with AD169-infected human embryonic lung fibroblasts [Maeda et al, 1994]. In contrast to this interpretation, we detected the expression of HCMV immediate early antigens (mab E13) as well as HCMV major capsid protein (mab 28-4) and massive cytopathogenicity in the most important organs.…”

Detection of DNA, mRNA and early antigen of the human cytomegalovirus using the immunomax technique in autopsy material of children with intrauterine infection

“…The nonspecific inflammatory lesions noted in the histopathological examination have been consistent with results of the earlier studies pertaining to morphological alterations in autopsied tissues in cases of the congenital HCMV syndrome [1,5,16,17]. Despite the symptoms of a diffuse intrauterine viral infection in all studied patients, death of vitally important organs (lungs, heart, brain) has not seemed directly connected with either the numbers of cells exhibiting evident cytopathic lesions (giant cells) or the expression of nucleic acids and early protein of HCMV at the tissue level.…”

“…The results are consistent with the study on dynamics of the inborn and the postnatally acquired HCMV infection. The latter studies have demonstrated prevalence of the early protein in the inborn infection with HCMV relative to the immediate early protein (IEA), which has dominated in the postnatally acquired infection [17]. In this study, the results on the detection of HCMV nucleic acids have confirmed the much higher sensitivity of the immunomax technique relative to classical hybridocytochemistry and the advantages of using ISH compared with immunocytochemistry.…”