Human herpesvirus-8: detection of novel herpesvirus-like DNA sequences in Kaposi's sarcoma and other lesions

Kaposi's sarcoma (KS) is a malignancy suspected of having an infectious etiology. Unique viral DNA sequences were recognized in KS lesions, using a novel technique that identifies small differences between two complex genomes. The virus had homology with the herpesvirus family, especially Epstein Barr virus (EBV), yet it was distinct from the known herpesviridae, and was appropriately named human herpesvirus 8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus (KSHV). HHV-8 DNA sequences were present in AIDS-associated KS, classic KS, African endemic KS, Mediterranean KS, iatrogenic KS, and KS in homosexual men without HIV infection. HHV-8 DNA sequences were also present in peripheral blood mononuclear cells (PBMC) of KS+ patients; body-cavity-based lymphomas in HIV positive patients without KS; and in tissue from a number of malignant and non-malignant lesions in patients without HIV infection. The role of HHV-8 in KS and other malignancies is not known. Viruses are notoriously trophic for lesional tissue. Therefore, in order to determine the role of HHV-8 in KS pathogenesis, HHV-8 needs to be isolated and shown to induce immortalization in a suitable system. Regardless of its role in KS, another human herpesvirus has been discovered, and the extent of its pathogenicity needs to be uncovered.Abbreviations KS Kaposi's sarcoma - HHV-8 human herpesvirus-8 - KSHV Kaposi's sarcoma-associated herpesvirus - EBV Epstein-Barr virus RDA representational difference analysis     

Human herpesvirus type 8 variants circulating in Europe, Africa and North America in classic, endemic and epidemic Kaposi's sarcoma lesions during pre-AIDS and AIDS era

Human herpesvirus-8 (HHV-8) variants have been found heterogeneously distributed among human populations living in diverse geographic regions, but their differential pathogenicity in Kaposi's sarcoma development remains controversial. In the present study, HHV-8 variant distribution has been analyzed in classic, iatrogenic, endemic as well as epidemic Kaposi's sarcoma (KS) during pre-AIDS and AIDS period (1971-2008) in countries with different KS incidence rate. DNA samples from cutaneous KS lesions of 68 patients living in Africa (n = 23, Cameroon, Kenya and Uganda), Europe (n = 34, Greece and Italy) and North America (n = 11) have been subjected to PCR amplification of HHV-8 ORF 26, T0.7, K1 and K14.1/15, followed by direct nucleotide sequencing and phylogenetic analysis. Among the 23 African samples, the majority of HHV-8 ORF 26 variants clustered with the subtype R (n = 12) and B (n = 5). Conversely, the viral sequences obtained from 45 European and North European tumors belonged mainly to subtype A/C (n = 36). In general, HHV-8 and K1 variant clustering paralleled that of ORF 26 and T0.7. Genotyping of the K14.1/15 loci revealed a large predominance of P subtype in all tumors. In conclusion, comparison of the HHV-8 sequences from classic or endemic versus AIDS-associated KS showed a strong linkage of the HHV-8 variants with specific populations, which has not changed during AIDS epidemic.     

Immunodeficiency-associated lymphoid proliferations (ALPS,HIV, and KSHV/HHV8)

The World Health Organization recognizes four categories of immunodeficiency-associated lymphoproliferative disorders (ID-LPDs): (1) lymphoproliferative diseases associated with primary immune disorders, (2) lymphomas associated with HIV infection, (3) post-transplant LPDs, and (4) other iatrogenic immunodeficiency-associated LPDs. Although these lesions are heterogeneous, due to their various underlying causes, they share several features, including frequent involvement of extranodal sites, diffuse aggressive histology, B-cell lineage, associated herpesvirus infection, and rapid clinical progression. The accurate diagnosis and treatment of the patients who develop immunodeficiency-associated LPDs often require careful evaluation of the morphology, immunophenotype, genotype, viral status, and clinical history. In this article, two of these four categories of ID-LPD are examined: lymphomas associated with HIV infections and lymphoproliferative diseases associated with primary immune disorders (PIDs), focusing on autoimmune lymphoproliferative syndrome (ALPS), as a representative disorder from this latter category.     

Expression of Kaposi's sarcoma-associated herpesvirus-encoded K10/10.1 protein in tissues and its interaction with poly(A)-binding protein

The K10/10.1 protein is encoded by a cluster of interferon regulatory factor (IRF) homologues in the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8, HHV-8) genome. In the present study, we showed that an anti-K10 antibody reacted with a 110-kDa protein encoded by the K10/10.1 gene of KSHV in KSHV-infected primary effusion lymphoma (PEL) cell lines. Expression of K10/10.1 protein was induced by phorbol ester in KSHV-infected cells. A reporter gene assay demonstrated that K10/10.1 protein did not influence promoter activity of human interferon genes, regardless of its homology to human IRFs. Poly(A)-binding protein (PABP) was identified as a partner of K10/10.1 protein. Immunoprecipitation revealed that K10/10.1 protein interacted with PABP specifically in PEL cell lines. IFA revealed co-localization of K10/10.1 protein and PABP in the nucleus of KSHV-infected cells. These data suggest that K10/10.1 protein may affect the translational status or stability of mRNA in host cells.     

Association of IL-6, IL-10 and CXCL10 serum concentrations with visceral Kaposi's sarcoma in people living with HIV/AIDS

Human gammaherpesvirus 8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma (KS), one of the most common cancers in people living with HIV/AIDS. It is believe that the course of both HIV and HHV-8 infection is associated with the imbalance of anti- and/or pro-inflammatory cytokines. Here, we evaluated the IL-6, TNF-α, IL-10, CCL2 and CXCL10 serum concentrations in HIV- and HIV/HHV-8 (without KS) individuals, and in patients with cutaneous or visceral AIDS-KS. Serum concentrations of IL-6, IL-10 and CXCL10 were significantly higher in the AIDS-KS group compared to HIV and HIV/HHV-8 individuals. Similarly, the concentrations of theses cytokines were higher in patients with visceral than in those with cutaneous AIDS-KS. The TNF-α concentration was significantly higher in the HIV group compared to HIV/HHV-8 (with and without KS) individuals, and CCL2 levels did not present significant difference among the groups. The HIV viral load was undetectable in all patients from the HIV and HIV/HHV-8 groups. On the other hand, in the AIDS-KS group, most patients had detectable HIV viral load. In this context, we believe that the cytokine levels in AIDS-KS may be result of a complex interaction between HIV, HHV-8 and immunity.     

<Emphasis Type="Italic">Pseudopycnadena tendu</Emphasis> sp. nov. (Digenea,Opecoelidae) in the yellow-spotted triggerfish <Emphasis Type="Italic">Pseudobalistes fuscus</Emphasis> (Perciformes,Balistidae) and additional opecoelids parasitizing fishes from the waters off New Caledonia

Pseudopycnadena tendu sp. nov. is described from the balistid Pseudobalistes fuscus from the waters off New Caledonia. It differs from the only other member of the genus P. fischthali Saad-Fares et Maillard, 1986, in its broad cirrus-sac, with the wide field of large gland-cells, its less nearly circular body shape, its dorsal excretory pore, its shorter post-testicular region, its relatively larger ventral sucker and its smaller eggs. The genus is re-defined to take these distinctions into account. Other opecoelid species reported from New Caledonia are Allopodocotyle epinepheli (Yamaguti, 1942) from Epinephelus cyanopodus, E. fasciatus and E. merra, Cainocreadium epinepheli (Yamaguti, 1934) from E. coeruleopunctatus, E. fasciatus and Variola louti, Hamacreadium mutabile (Linton, 1910) from Lutjanus fulviflamma and L. kasmira, Helicometra epinepheli Yamaguti, 1934 from E. fasciatus and E. merra, Orthodena tropica Durio et Manter, 1968 from Lethrinus lentjan, Pacificreadium serrani (Nagaty et Abdel-Aal, 1962) from Plectropomus leopardus and Pseudoplagioporus interruptus Durio et Manter, 1968 from Lethrinus rubrioperculatus.

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Résumé Pseudopycnadena tendu sp. nov. est décrit du baliste Pseudobalistes fuscus pêché en Nouvelle-Calédonie. L’espèce diffère du seul autre membre du genre, P. fischthali Saad-Fares et Maillard, 1986, par son sac du cirre plus épais avec un champ large de cellules glandulaires, sa forme du corps presque circulaire, son pore excréteur dorsal, sa partie post-testiculaire plus courte, sa ventouse ventrale relativement plus grande et ses œufs plus petits. Le genre est redéfini pour prendre en compte ces distinctions. D’autres Opecoelidae sont mentionnés de Nouvelle-Calédonie: Allopodocotyle epinepheli (Yamaguti, 1942) de Epinephelus cyanopodus, E. fasciatus et E. merra, Cainocreadium epinepheli (Yamaguti, 1934) de E. coeruleopunctatus, E. fasciatus et Variola louti, Hamacreadium mutabile (Linton, 1910) de Lutjanus fulviflamma et L. kasmira, Helicometra epinepheli Yamaguti, 1934 de E. fasciatus et E. merra, Orthodena tropica Durio et Manter, 1968 de Lethrinus lentjan, Pacificreadium serrani (Nagaty et Abdel-Aal, 1962) de Plectropomus leopardus et Pseudoplagioporus interruptus Durio et Manter, 1968 de Lethrinus rubrioperculatus.