Cytomegalovirus infection after orthotopic liver transplantation is restricted by a pre‐existing antiviral immune response of the recipient

Abstract

Infection of the liver by the human cytomegalovirus (HCMV) frequently occurs after orthotopic liver transplantation (OLT). However, the role of viral replication and the inflammatory reaction in the development of HCMV-associated liver dysfunction is unclear. To address this question in vivo, 84 liver biopsy specimens from 74 patients who received an orthotopic liver transplant were investigated by immunohistochemical detection of viral antigens and cell type specific marker proteins. The extent of viral replication was correlated with the HCMV antibody status of donor and recipient. HCMV immediate early antigens were found in 25 of 84 liver tissue sections investigated, hepatocytes being the predominant target cells. Bile duct epithelial cells, endothelial cells, mesenchymal cells and sinusoidal lining cells were also found susceptible to HCMV infection. The detection of viral capsid antigens, nuclear inclusions in infected cells and foci of infected cells were suggestive of permissive infection in these cells. In 25 HCMV-positive liver biopsy specimens, the median extent of HCMV infection was 0.33 (0.02-5.67) infected cells/mm(2) liver tissue. Primary infection of liver transplant recipients (D+/R-) was associated with a significantly higher extent of organ involvement as compared to reinfection or reactivation (D+/R+). In contrast, the extent of inflammatory infiltrates in areas of infected liver cells was higher in tissues of patients with pre-existing immunoreactivity (R+) compared to patients without pre-existing immunoreactivity (R-). In conclusion, these results favour the assumption that the immune response to HCMV is effective in restricting viral spread in the liver.

HIV Superinfection

“…Similar to other chronic viral infections, such as those with cytomegalovirus and Epstein-Barr virus, infection of an individual with a second viral strain (dual infection) [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] occurs in HIV infection. The terminology related to dual infection is important.…”

The Human Cytomegalovirus, from Oncomodulation to Oncogenesis

“…Human mammary epithelial cells (HMECs) are productively infected by HCMV clinical isolates with low levels of replication [ 15 , 16 ]. HCMV also replicates in renal epithelial cells [ 16 ] and hepatocytes are permissive for HCMV replication with a limited viral production [ 12 , 17 , 18 ]. After prolonged infection in vitro of human embryonic fibroblasts, large syncytia appear in cultures with typical HCMV intranuclear inclusion bodies [ 19 ].…”

Visualization and Microscopic Quantification of HCMV-Peptide–Specific Cytotoxic T Lymphocytes Using Tetramer Binding

“…Additional information about the cellular immunoreaction in the infected tissues might be beneficial to support the obvious effectiveness of adoptive T cell transfer. Immunohistochemical analyses in the past demonstrated the meaning of lymphocytes to control HCMV tissue infection (2). To shed light on the distribution of virus-specific lymphocytes in infected organisms, a protocol for microscopic detection would be beneficial.…”