Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8)

Abstract

A BSTR ACTThe genome of the Kaposi sarcomaassociated herpesvirus (KSHV or HHV8) was mapped with cosmid and phage genomic libraries from the BC-1 cell line.

Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas)

“…17 Identical sequence patterns have been found for cell line HBL-6. 17 HHV-8 is unique in encoding a number of pro- teins mimicking cell cycle regulatory, receptor and signaling proteins, eg homologues of the cytokine interleukin-6 (IL-6) and the chemokines macrophage inflammatory protein-1 alpha and beta (MIP-1␣/␤), interferon regulatory factor (IRF), the IL-8 receptor (IL-8R), the complement receptor-2 (CR2/CD21), the adhesion molecule NCAM (CD56), the antiapoptotic proto-oncogene Bcl-2, and the cell cycle regulator cyclin D 12,13,17,39 (Table 6). The viral IL-6 (vIL-6) has 62% amino acid similarity to the human IL-6 (huIL-6); despite regions of sequence dissimilarity between vIL-6 and huIL-6, the viral interleukin has biological activity in functional bioassays with the mouse plasmacytoma cell line B9 and the human myeloma cell line INA-6 which undergo apoptosis in the absence of IL-6.…”

“…While the presence of these two viruses in combination appears to be unique to this type of lymphoma, the detection of HHV-8+ EBV-negative cases questions any synergistic action of HHV-8 and EBV in the pathogenesis of PEL, suggesting that EBV is not an absolute requirement for the manifestation of PEL. 8 Although the role of HHV-8 in the etiology of these diseases has not been fully established, some hypotheses on the potential mechanisms of pathogenesis have been forwarded: for instance, the virus encodes several genes with oncogenic potential as well as homologues of cytokines, cytokine receptors, chemokines and signal transducers 1,17 (see below for Table 2 for details on these cell lines). Note the striking variability in cell size, cell membrane contours, nuclear size, polynuclearity and form, deep cytoplasmic basophilia, and other morphological features.…”

Classic Kaposi Sarcoma in the United States over the last two decades: A clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma

“…31 HHV-8 is tightly connected as the etiologic agent in Kaposi Sarcoma with roles for the viral lytic gene and the lack of specific HHV-8 T-cell immune response in patients with Kaposi Sarcoma being recently documented. 21,[31][32][33][34][35][36][37] This virus induces cytokines, which are known to play a role in the development of Classic Kaposi Sarcoma. 10,38 It is hypothesized that lymphoproliferative disorders or other malignancies might pass HHV-8 to its lytic phase, in sites of latency, 39 and 40 Although the majority of our subgroup of Classic Kaposi Sarcoma patients, representing a cross-section oflesional stage and patient gender, were positive by PCR analysis for HHV-8, one case with ample material was negative.…”

Virus proteins similar to human proteins as possible disturbance on human pathways

“…Many of these KSHV genes represent pirated versions of cellular genes, including those encoding molecules involved in cell cycle control, apoptosis prevention, immune system regulation and inter-and intracellular communication, thus harboring proangiogenic and oncogenic potential (Russo et al 1996), which suggests the possibility of the obtained protein related to oncoviruses.…”