Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells.

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease usually encountered in the context of primary EBV infection. In most analyzed cases, EBV has been found predominantly in T cells. We describe the novel finding of high EBV genome numbers within circulating natural killer cells in adult patients with EBV-HLH.

Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells.

Epstein-Barr virus (EBV), an orally transmitted herpesvirus, efficiently targets B lymphocytes through binding of the viral envelope glycoprotein gp350 to the complement receptor CD21. How the virus accesses epithelial cells is less well understood, because such cells are largely resistant to infection with cell-free virus in vitro. Here, we show that, after binding to primary B cells, most Epstein-Barr virions are not internalized but remain on the B cell surface and from there can transfer efficiently to CD21-negative epithelial cells, increasing epithelial infection by 10(3)- to 10(4)-fold compared with cell-free virus. Transfer infection is associated with the formation of B cell-epithelial conjugates with gp350/CD21 complexes focused at the intercellular synapse; transfer involves the gp85 and gp110 viral glycoproteins but is independent of gp42, the HLA class II ligand that is essential for B cell entry. Therefore, through efficient binding to the B cell surface, EBV has developed a means of simultaneously accessing both lymphoid and epithelial compartments; in particular, infection of pharyngeal epithelium by orally transmitted virus becomes independent of initial virus replication in the B cell system.

Defective infectious particles and rare packaged genomes produced by cells carrying terminal-repeat-negative epstein-barr virus.

The Epstein-Barr virus (EBV) lytic program includes lytic viral DNA replication and the production of a viral particle into which the replicated viral DNA is packaged. The terminal repeats (TRs) located at the end of the linear viral DNA have been identified as the packaging signals. A TR-negative (TR(-)) mutant therefore provides an appropriate tool to analyze the relationships between EBV DNA packaging and virus production. Here, we show that supernatants from lytically induced 293 cells carrying TR mutant EBV genomes (293/TR(-)) contain large amounts of viral particles devoid of viral DNA which are nevertheless able to bind to EBV target cells. This shows that viral DNA packaging is not a prerequisite for virion formation and egress. Rather surprisingly, supernatants from lytically induced 293/TR(-) cells also contained rare infectious viruses carrying the viral mutant DNA. This observation indicates that the TRs are important but not absolutely essential for virus encapsidation.

Differentiation of human cytomegalovirus genotypes in immunocompromised patients on the basis of UL4 gene polymorphisms.

The variety of clinical manifestations of human cytomegalovirus infection probably results from both viral and host factors. Because genetic markers that span the viral genome are needed to identify such viral factors, polymorphisms at the UL4 gene locus were analyzed. DNA sequence analyses revealed 4 UL4-based genotypes, 2 of which were closely related but distinguishable by an uncommon polymorphism that results in overexpression of gpUL4. Similarities in the spectra of polymorphisms detected in various sets of samples reveal that all UL4 types infect a diversity of organs in different patient groups and in different geographic locales. Simultaneous infection by >1 UL4 type is common in AIDS patients. Data from sequencing analyses and from a rapid and simple UL4 typing assay did not detect linkage between UL4 and glycoprotein B types, which suggests that UL4 genotyping should be useful for studies that attempt to identify cytomegalovirus genes involved in disease pathogenesis.