Rare Diseases Symptoms Automatic Extraction

Modulation of Kaposi's sarcoma-associated herpesvirus interleukin-6 function by hypoxia-upregulated protein 1.

[primary effusion lymphoma]

Kaposi's sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8) is linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV expresses several proteins that modulate host cell signaling pathways. One of these proteins is viral interleukin-6 (vIL-6), which is a homolog of human IL-6 (hIL-6). vIL-6 is able to prevent apoptosis and promote proinflammatory signaling, angiogenesis, and cell proliferation. Although it can be secreted, vIL-6 is mainly an intracellular protein that is retained in the endoplasmic reticulum (ER). We performed affinity purification and mass spectrometry to identify novel vIL-6 binding partners and found that a cellular ER chaperone, hypoxia-upregulated protein 1 (HYOU1), interacts with vIL-6. Immunohistochemical staining reveals that both PEL and KS tumor tissues express significant amounts of HYOU1. We also show that HYOU1 increases endogenous vIL-6 protein levels and that HYOU1 facilitates vIL-6-induced JAK/STAT signaling, migration, and survival in endothelial cells. Furthermore, our data suggest that HYOU1 also modulates vIL-6's ability to induce CCL2, a chemokine involved in cell migration. Finally, we investigated the impact of HYOU1 on cellular hIL-6 signaling. Collectively, our data indicate that HYOU1 is important for vIL-6 function and may play a role in the pathogenesis of KSHV-associated cancers.KSHV vIL-6 is detectable in all KSHV-associated malignancies and promotes tumorigenesis and inflammation. We identified a cellular protein, called hypoxia-upregulated protein 1 (HYOU1), that interacts with KSHV vIL-6 and is present in KSHV-infected tumors. Our data suggest that HYOU1 facilitates the vIL-6-induced signaling, migration, and survival of endothelial cells.

Diseases presenting "lymphoma" symptom

  • adrenal incidentaloma
  • alpha-thalassemia
  • carcinoma of the gallbladder
  • cushing syndrome
  • dedifferentiated liposarcoma
  • erdheim-chester disease
  • erythropoietic protoporphyria
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • familial hypocalciuric hypercalcemia
  • focal myositis
  • hirschsprung disease
  • hodgkin lymphoma, classical
  • kabuki syndrome
  • liposarcoma
  • locked-in syndrome
  • monosomy 21
  • oculocutaneous albinism
  • primary effusion lymphoma
  • severe combined immunodeficiency
  • systemic capillary leak syndrome
  • waldenström macroglobulinemia
  • wiskott-aldrich syndrome

This symptom has already been validated