Tropism of human herpesvirus 8 for peripheral blood lymphocytes in patients with Castleman's disease

Abstract

Summary. Multicentric Castleman's disease (MCD), also called multicentric angiofollicular lymphoid hyperplasia, is a systemic lymphoproliferative disorder causing fever, lymphadenopathy and splenomegaly. Recently, Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) DNA sequences have been detected in cases of MCD. We examined HHV-8 DNA sequences in the peripheral blood mononuclear cells (PBMCs) of two HIVnegative patients with MCD and in PBMCs and the lymph node of a HIV-negative patient with localized Castleman's disease (LCD) by the polymerase chain reaction. The novel sequences were detected in all DNA samples. Furthermore, the sequences were detected in only the CD19 þ Blymphocyte fraction of the patient with LCD as previously reported. However, the sequences were detected in CD19 þ B-lymphocyte and CD2þ T-lymphocyte fractions of two patients with MCD. These results suggest that HHV-8 has tropisms for both B lymphocytes and T lymphocytes in Castleman's disease.

Human Herpesvirus 8-Encoded vGPCR Activates Nuclear Factor of Activated T Cells and Collaborates with Human Immunodeficiency Virus Type 1 Tat

“…We first tested NF-AT activation by vGPCR in Tlymphoid (Jurkat) cells because T cells express high levels of NF-AT protein, making it easy to measure NF-AT activation. T cells of patients with HHV-8-related diseases are infected, although not abundantly (41,42,45; M. C. Sirianni, L. Vincenzi, S. Topino, E. Scala, A. Angeloni, R. Gonnella, S. Uccini, and A. Faggioni, Letter, J. Infect. Dis.…”

Direct Interactions of Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Protein with the Cellular Protein Octamer-1 and DNA Are Critical for Specifying Transactivation of a Delayed-Early Promoter and Stimulating Viral Reactivation

“…Like other gammaherpesviruses, KSHV is lymphotropic (1,5,6,20,30,35,98) and replicates both latently and lytically (59,70,71,105). Following primary infection, KSHV establishes latency in CD19 ϩ B cells (and possibly other cells types) (7).…”

“…Complexes were washed extensively, beads were boiled in 2ϫ Laemmli buffer, and bound proteins were displayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 35 S-labeled proteins were visualized by autoradiography after amplifying signals in 0.5 M salicylic acid.…”

Signaling Activities of Gammaherpesvirus Membrane Proteins

“…A serological study showed that over 95% of rhesus monkeys are strongly positive for the presence of antibodies to this herpesvirus, suggesting that rhesus monkeys are a natural host for RRV infection (31). While specific diseases associated with RRV remain to be determined, some of the naïve seronegative rhesus macaques inoculated with RRV developed lymphadenopathy and vascular hyperplasia (85,140) similar to that observed in KSHV-infected men (18,66,130). Furthermore, inoculated monkeys remained persistently infected with RRV (85).…”

“…MCD is an atypical lymphoproliferative disorder that includes hyperplasia, lymphadenopathy, and splenomegaly. Both HIV-infected and -uninfected individuals develop MCD, although there is a high rate of KSHV infection in the lymph nodes of HIV patients with MCD (18,66,130). It has been demonstrated that viral interleukin-6 (IL-6) acts as an autocrine or paracrine factor in the lymphoproliferative processes common to both BCBLs and MCD (111,131).…”