Epstein-Barr virus (EBV) infection in infectious mononucleosis: virus latency, replication and phenotype of EBV-infected cells.
Primary Epstein-Barr virus (EBV) infection may manifest itself as a benign lymphoproliferative disorder, infections mononucleosis (IM). EBV infection has been characterized in lymphoreticular tissues from nine patients with IM using the abundantly expressed EBV-encoded nuclear RNAs (EBERs) as a marker of latent infection. Expression of the virus-encoded nuclear antigen (EBNA) 2 and of the latent membrane protein (LMP) 1 was seen in variable proportions of cells in all cases. Double labelling revealed heterogeneous expression patterns of these proteins. Thus, in addition to cells revealing phenotypes consistent with latencies I (EBNA2-/LMP1-) and III (EBNA2+/LMP1+), cells displaying a latency II pattern (EBNA2-/LMP1+) were observed. Cells expressing EBNA2 but not LMP1 were also detected; whilst this may represent a transitory phenomenon, the exact significance of this observation is at present uncertain. EBER-specific in situ hybridization in conjunction with immunohistochemistry revealed expression of the EBERs mainly in B-lymphocytes, many of which showed features of plasma cell differentiation. By contrast, convincing evidence of latent EBV infection was not found in T-cells, epithelial or endothelial cells. Double-labelling immunohistochemistry revealed expression of the replication-associated BZLF1 protein in small lymphoid cells, often showing plasmacytoid differentiation. There was no unambiguous expression of this protein in other cell types. These results suggest that B-cells are the primary target of EBV infection and that plasma cells may be a source of infectious virus found in the saliva of IM patients.
Niedobitek
G
G
Department of Pathology, University of Birmingham, U.K.
Agathanggelou
A
A
Herbst
H
H
Whitehead
L
L
Wright
D H
DH
Young
L S
LS
D000956:Antigens, Viral / Q000032:analysis; D001402:B-Lymphocytes / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007244:Infectious Mononucleosis / Q000821:virology*; D010641:Phenotype; D010950:Plasma Cells / Q000821:virology; D014763:Viral Matrix Proteins / Q000032:analysis; D017735:Virus Latency; D014779:Virus Replication
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins