Primary HHV-8 infection and reactivation of infection may be associated with nonneoplastic complications in immunosuppressed patients.

Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign , atypical, and malignant lymphoid lesions , which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens , characteristic either of the early (p41) or late (p101K , gp106, and gp116) phases of the viral cycle , was applied to the lymphoid tissues from 15 non-Hodgkin's lymphomas , 14 Hodgkin's disease cases , 5 angioimmunoblastic lymphadenopathies with dysproteinemia , 14 reactive lymphadenopathies , and 2 cases of sinus histiocytosis with massive lymphadenopathy (RosaiDorfman disease). In lymphomatous tissues , the expression of late antigens was documented only in reactive cells , and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called "mummified" Reed-Sternberg cells, in two Hodgkin's disease cases. In reactive lymphadenopathies , the HHV-6 late antigen-expressing cells were plasma cells , histiocytes , and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease , the p101K showed an intense staining in follicular dendritic cells of germinal centers , whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes , which represent the histological hallmark of the disease.

The p12 I protein, encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 (HTLV-1), is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi. Although p12 I contains 4 minimal proline-rich, src homology 3-binding motifs (PXXP), a characteristic commonly found in proteins involved in signaling pathways, it has not been known whether p12 I has a role in modulating intracellular signaling pathways. This study demonstrated that p12 I binds to the cytoplasmic domain of the interleukin-2 receptor (IL-2R) ␤ chain that is involved in the recruitment of the Jak1 and Jak3 kinases. As a result of this interaction, p12 I IntroductionHuman T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL), 1 and its genome carries genetic information for the structural and enzymatic proteins, the regulatory proteins Tax and Rex, and other open reading frames (orfs) encoding small proteins with largely unknown functions. 2-5 HTLV-1 infects and immortalizes primary human T cells in vitro, and after several months, these cells acquire the ability to grow in the absence of interleukin-2 (IL-2). 1 The switch to IL-2 independence correlates in most cases with acquisition of a constitutive activation of the Jak/signal transducers and activators of transcription (STAT) pathway 6-8 and decreased expression of the src homology 2-containing tyrosine phosphatase 1 protein, 9 which regulates signaling from several hematopoietic surface receptors. 10 HTLV-1 also confers longevity on T cells in vivo, since expansion of T cells with identical integrations for HTLV-1 can be found at several-year intervals in the same infected individuals. 11 These findings raise the question of how CD4 ϩ T cells carrying the HTLV-1 provirus can expand and survive for a long time in vivo.The HTLV-1 p12 I protein, a hydrophobic protein resident in the endoplasmic reticulum (ER) and Golgi 58 that is encoded by the 3Ј end orf I of the viral genome, 12 forms dimers, 13 has weak oncogenic properties, and binds to the p16 subunit of the vacuolar hydrogen adenosine diphosphatase (H ϩ ATPase). 14 Expression of p12 I in infected cells is suggested by the presence of transcripts in cultured 3,5,15 and ex vivo cells from individuals infected with HTLV-1. 5 The orf I is likely expressed in vivo because antibodies (Abs) and cytotoxic T lymphocytes to peptides from the orf I protein have been detected. 16,17 Importantly, ablation of the splice acceptor site for the singly spliced p12 I messenger RNA from a molecular clone of HTLV-1 impaired viral infectivity in a rabbit model in vivo. 18 This may be partly related to the finding that p12 I interferes with major histocompatibility complex class I (MHC I) heavy-chain trafficking and may facilitate escape of HTLV-1-infected cells from the host's immune surveillance. 58 We previously reported that p12 I also binds the IL-2 receptor (IL-2R) ␤ and ␥ c chains and affects their expression on the cell surface. 19 IL-2 is an essential cytokine for the growth and s...

No abstract