Hypoxia induces lytic replication of Kaposi sarcoma–associated herpesvirus

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3244-3250 ◽  
Author(s):  
David A. Davis ◽  
Andrea S. Rinderknecht ◽  
J. Paul Zoeteweij ◽  
Yoshiyasu Aoki ◽  
Elizabeth L. Read-Connole ◽  
...  
Keyword(s):  
Potential Role ◽  
Primary Effusion Lymphoma ◽  
Hypoxia Inducible Factor ◽  
Kaposi Sarcoma ◽  
Lytic Replication ◽  
Substantial Evidence ◽  
Hypoxia Inducible Factor 1 ◽  
Latently Infected ◽  
Acute And Chronic Exposure

Abstract There is substantial evidence that Kaposi sarcoma–associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1% O2) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS.

scholarly journals A role of hypoxia-inducible factor 1 alpha in Murine Gammaherpesvirus 68 (MHV68) lytic replication and reactivation from latency

2019 ◽  
Vol 15 (12) ◽  
pp. e1008192 ◽  
Author(s):  
Darlah M. López-Rodríguez ◽  
Varvara Kirillov ◽  
Laurie T. Krug ◽  
Enrique A. Mesri ◽  
Samita Andreansky
Keyword(s):  
Hypoxia Inducible Factor ◽  
Lytic Replication ◽  
Murine Gammaherpesvirus ◽  
Hypoxia Inducible Factor 1 ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals Histomorphological Assessment of Formalin versus Nonformalin Fixatives in Diagnostic Surgical Pathology

2020 ◽  
Vol 12 (04) ◽  
pp. 271-275
Author(s):  
Jayaprakash Kubalady Shetty ◽  
Hannah Fathima Babu ◽  
Kishan Prasad Hosapatna Laxminarayana
Keyword(s):  
Methyl Alcohol ◽  
Potential Role ◽  
Tissue Architecture ◽  
Substantial Evidence ◽  
Diagnostic Pathology ◽  
Rapid Fixation ◽  
Chromatin Texture ◽  
Upper Respiratory ◽  
Potential Human Health

Abstract Introduction Fixation is the critical step in the preservation of tissues in diagnostic pathology. The formalin is an economical and excellent fixative with the inherent property of adequate fixation. The well-established side effects of formalin include mucosal irritation, upper respiratory diseases, and corrosive injury to the gastrointestinal tract. In addition, substantial evidence exists regarding the potential role of formaldehyde as a human carcinogen. The carcinogenic and toxic effects of formalin encourage searching for alternative fixatives for tissue fixation. However, “the formalin dogma” has severely hampered the search for alternative fixatives for many years. Material and Methods Ninety tissues of liver and skeletal muscle obtained during autopsies were immersed in adequate amounts of the following fixatives: formalin (10%), methyl alcohol (70%), and acetone (100%). The comparison among the three was made based on time for fixation, preservation of tissue architecture, cell borders, cytoplasm, nuclear contours, chromatin texture, and uniformity of staining. Results The tissue preserved in formalin undergoes rapid fixation compared with alcohol and acetone. The tissue architecture, cell border characteristics of alcohol and acetone was found satisfactory compared with formalin. The cytoplasm and nuclear contour were superior with the formalin. The chromatin texture and uniformity of staining were similar with all the three fixatives. Conclusion The formalin is considered superior to most of the parameters, whereas both methyl alcohol and acetone showed nearly equivalent scores. Hence, owing to the potential human health hazards and carcinogenicity of formalin, no rational reasons hamper the complete substitution of formalin with alternative fixatives such as alcohol and acetone in diagnostic pathology and medical research.

scholarly journals The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment

2016 ◽  
Vol 37 (6) ◽  
pp. 969-977 ◽  
Author(s):  
Osigbemhe Iyalomhe ◽  
Sabina Swierczek ◽  
Ngozi Enwerem ◽  
Yuanxiu Chen ◽  
Monica O. Adedeji ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Lytic Replication-Defective Kaposi's Sarcoma-Associated Herpesvirus: Potential Role in Infection and Malignant Transformation

2004 ◽  
Vol 78 (20) ◽  
pp. 11108-11120 ◽  
Author(s):  
Jian-Hong Deng ◽  
Yan-Jin Zhang ◽  
Xin-Ping Wang ◽  
Shou-Jiang Gao
Keyword(s):  
Malignant Transformation ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Potential Role ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Screening Methods ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Defective viruses often have pivotal roles in virus-induced diseases. Although Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), defective KSHV has not been reported. Using differential genetic screening methods, we show that defective KSHV is present in KS tumors and PEL cell lines. To investigate the role of defective viruses in KSHV-induced pathogenesis, we isolated and characterized a lytic replication-defective KSHV, KV-1, containing an 82-kb genomic deletion of solely lytic genes. Cells harboring KV-1 escaped G0/G1 apoptosis induced by spontaneous lytic replication occurred in cells infected with regular KSHV but maintained efficient latent replication. Consequently, KV-1-infected cells had phenotypes of enhanced cell proliferation and transformation potentials. Importantly, KV-1 was packaged as infectious virions by using regular KSHV as helpers, and KV-1-like variants were detected in cultures of two of five KSHV cell lines and 1 of 18 KS tumors. These results point to a potential role for defective viruses in the regulation of KSHV infection and malignant transformation.

scholarly journals Hypoxia-inducible factor–1 and associated upstream and downstream proteins in the pathophysiology and management of glioblastoma

2014 ◽  
Vol 37 (6) ◽  
pp. E8 ◽  
Author(s):  
Matthew Womeldorff ◽  
David Gillespie ◽  
Randy L. Jensen
Keyword(s):  
Cellular Response ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Poor Patient ◽  
Growth Development ◽  
The Relationship ◽  
Insight Into ◽  
Upstream Regulators

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an exceptionally poor patient outcome despite aggressive therapy including surgery, radiation, and chemotherapy. This aggressive phenotype may be associated with intratumoral hypoxia, which probably plays a key role in GBM tumor growth, development, and angiogenesis. A key regulator of cellular response to hypoxia is the protein hypoxia-inducible factor–1 (HIF-1). An examination of upstream hypoxic and nonhypoxic regulation of HIF-1 as well as a review of the downstream HIF-1–regulated proteins may provide further insight into the role of this transcription factor in GBM pathophysiology. Recent insights into upstream regulators that intimately interact with HIF-1 could provide potential therapeutic targets for treatment of this tumor. The same is potentially true for HIF-1–mediated pathways of glycolysis-, angiogenesis-, and invasion-promoting proteins. Thus, an understanding of the relationship between HIF-1, its upstream protein regulators, and its downstream transcribed genes in GBM pathogenesis could provide future treatment options for the care of patients with these tumors.

scholarly journals Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1599-1601 ◽  
Author(s):  
Yoshiyasu Aoki ◽  
Robert Yarchoan ◽  
James Braun ◽  
Aikichi Iwamoto ◽  
Giovanna Tosato
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Human Immunodeficiency Virus ◽  
Potential Role ◽  
Kaposi Sarcoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Immunodeficiency Virus ◽  
Endothelial Growth Factor ◽  
Primary Effusion Lymphomas

Abstract Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL.

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