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The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and was associated with lytic EBV gene expression, resulting in increased tumor formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders in humans. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication.

shown to function as a CRM1-independent nuclear mRNA export factor, promoting export of mRNAs that are poor substrates for splicing. The ␥-herpesvirus ORF57 protein, and its ␣-1 herpesvirus ICP27 counterpart both export RNA through pathways involving REF and TAP proteins, although divergence of these herpesvirus subfamilies occurred some 180 -210 million years ago. The TAP-mediated cellular mRNA export pathway is CRM1-independent. However, human immunodeficiency virus type 1 Rev protein-mediated RNA export, which is CRM1-dependent, was considerably inhibited by ORF57, suggesting that Rev and ORF57 compete for a common export component. These data strengthen arguments that TAP and CRM1 pathways converge in accessing similar components of the nuclear pore complex. We propose that ORF57-mediated RNA export may use different export factors to accommodate the KSHV-infected host cell environments, for example, in B-cells or endothelial cells and during the different phases of lytic virus replication.

The authors provide the first ultrastructural description of the marine holotrich ciliate Mesodinium rubrum and of its unusual "incomplete symbionts," consisting of numerous functional chloroplasts associated with distinctive nonciliate mitochondria but apparently lacking associated nuclei. The pigment characteristics suggest a cryptomonad origin for the chloroplasts but they are traversed by lamellae that are either ungrouped or in groups of three's, this being contrary to ultrastructural observations on cryptomonads to date. Unusual ultrastructural features of the ciliate include the lack of alveoli in the very thin pellicle and two types of ciliary differentiation: the presence of lateral packing material in some of the cilia grouped to form cirri, and narrow distal portions from which the nine peripheral microtubule duplets are excluded. The cytostome is greatly reduced and the ciliate usually swims backwards. The problem as to the degree of permanence reflected by these features, including whether the symbiotic state is obligate or not, was not resolved. The authors discuss the evidence bearing on this question.The paper also reviews the ecology and taxonomy of the ciliate. Fifty instances of its occurrence, often in conjunction with nontoxic "red water," are summarised. The species has an extremely wide geographic distribution, including both polar and equatorial waters. Red water caused by the species occurs either within extreme coastal localities (bays, inlets) or in the vicinity of offshore upwelling. Field studies demonstrated that the ciliate–chloroplast consortium is a functional autotroph capable of playing the role of primary producer.Taxonomic difficulties are summarised. Previous designations of the species to the genus Cyclotrichium are considered inappropriate. Detailed study of widely spread populations is needed to determine the degree of taxonomic confusion involved.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently discovered human herpesvirus. It is the aetiological agent of Kaposi's sarcoma (KS), a tumour frequently affecting AIDS patients not receiving treatment. KSHV is also a likely cause of two lymphoproliferative diseases: multicentric Castleman's disease and primary effusion lymphoma. The study of KSHV offers exciting challenges for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host. To facilitate these processes, approximately one-quarter of KSHV genes encode cellular homologues or unique proteins that have immunomodulatory roles in cytokine production, apoptosis, cell signalling and the immunological synapse. The activities of these molecules are considered in the present review and the positions of their genes are mapped from a complete KSHV genome sequence derived from a KS biopsy. The understanding gained enables the significance of different components of the immune response in protection against KSHV infection to be evaluated. It also helps to unravel the complexities of cellular and immunological pathways and offers the potential for exploiting viral immunomodulators and derivatives in disease therapy.

Infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the development of Kaposi's sarcoma (KS), a highly inflammatory angiogenic tumor of endothelial cells commonly found in untreated AIDS patients. Angiopoietin 2 (Ang-2) modulates the vasculature during inflammation and angiogenesis, but the mechanism by which KSHV regulates Ang-2 expression has not been investigated. Here, we show that KSHV infection of primary human umbilical vein endothelial cells induced the expression and release of Ang-2, which in turn was required for KSHV-induced paracrine-dependent angiogenesis in vivo. Ang-2 was strongly expressed in small vessels and spindle tumor cells in KS tumors. Mechanistically, KSHV activated the Ang-2 promoter via AP-1 and Ets1 transcriptional factors, which were mediated by ERK, JNK, and p38 mitogenactivated protein kinase (MAPK) pathways. Our findings demonstrate the importance of Ang-2 in KS angiogenesis and define a novel role for AP-1 and MAPK pathways in regulating angiogenesis. This study also illustrates a distinct mechanism by which a tumor virus modulates vasculature to promote tumorigenesis and exemplifies the convergence of oncogenesis and angiogenesis pathways in tumor development.

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