scholarly journals Interferon-Induced Transmembrane Proteins Inhibit Infection by the Kaposi’s Sarcoma-Associated Herpesvirus and the Related Rhesus Monkey Rhadinovirus in a Cell-Specific Manner

mBio ◽  
2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Bojan F. Hörnich ◽  
Anna K. Großkopf ◽  
Candice J. Dcosta ◽  
Sarah Schlagowski ◽  
Alexander S. Hahn
Keyword(s):  
Rhesus Monkey ◽  
Mechanism Of Action ◽  
Kaposi's Sarcoma ◽  
Transmembrane Proteins ◽  
Kaposi’S Sarcoma ◽  
Antiviral Effect ◽  
First Line ◽  
Specific Manner ◽  
A Cell ◽  
Kaposi’S Sarcoma Associated Herpesvirus

IFITM proteins are the first line of defense against infection by many pathogens and may also have therapeutic importance, as they, among other effectors, mediate the antiviral effect of interferons. Neither their function against herpesviruses nor their mechanism of action is well understood.

scholarly journals Interferon-Induced Transmembrane Proteins Inhibit Infection by the Kaposi’s Sarcoma-Associated Herpesvirus and the Related Rhesus Monkey Rhadinovirus in a Cell Type-Specific Manner.

2021 ◽  
Author(s):  
Bojan Fabio Hörnich ◽  
Anna Katharina Großkopf ◽  
Candice Judith DCosta ◽  
Sarah Schlagowski ◽  
Alexander Siegfried Hahn
Keyword(s):  
Rhesus Monkey ◽  
Influenza A ◽  
Kaposi's Sarcoma ◽  
Gene Knockout ◽  
Transmembrane Proteins ◽  
Kaposi’S Sarcoma ◽  
Cell Type ◽  
A Cell ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

The interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral proteins that inhibit the entry of enveloped viruses. We analyzed the effect of IFITMs on the gamma2-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and the closely related rhesus monkey rhadinovirus (RRV). We used CRISPR/Cas9-mediated gene knockout to generate A549, human foreskin fibroblast (HFF) and human umbilical vein endothelial cells (HUVEC) with combined IFITM1/2/3 knockout and identified IFITMs as cell type-dependent inhibitors of KSHV and RRV infection in A549 and HFF but not HUVEC. IFITM overexpression revealed IFITM1 as the relevant IFITM that inhibits KSHV and RRV infection. Fluorescent KSHV particles did not pronouncedly colocalize with IFITM-positive compartments. However, we found that KSHV and RRV glycoprotein-mediated cell-cell fusion is enhanced upon IFITM1/2/3 knockout. Taken together, we identified IFITM1 as a cell type-dependent restriction factor of KSHV and RRV that acts at the level of membrane fusion. Strikingly, we observed that the endotheliotropic KSHV circumvents IFITM-mediated restriction in HUVEC despite high IFITM expression, while influenza A virus (IAV) glycoprotein-driven entry into HUVEC is potently restricted by IFITMs even in the absence of interferon.

scholarly journals Kaposi's Sarcoma-associated Herpesvirus-encoded Viral Interleukin-6 Is Secreted and Modified Differently Than Human Interleukin-6

2004 ◽  
Vol 279 (50) ◽  
pp. 51793-51803 ◽  
Author(s):  
Mark B. Meads ◽  
Peter G. Medveczky
Keyword(s):  
Interleukin 6 ◽  
Kaposi's Sarcoma ◽  
Signal Sequence ◽  
Kaposi’S Sarcoma ◽  
Receptor Activation ◽  
High Affinity Receptor ◽  
A Cell ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Intracellular Binding ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Viral interleukin-6 (vIL-6) is a homolog of cellular IL-6 that is encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome. vIL-6 binds to the IL-6 signal transducer gp130 without the cooperation of the IL-6 high affinity receptor to induce STAT3 DNA binding and cell proliferation. Although vIL-6 is believed to be important in the pathogenesis of KSHV-induced diseases, its secretion and post-translational modifications have not previously been characterized. Pulse-chase analysis revealed that the half-time of vIL-6 secretion is ∼8-fold longer than that of human IL-6. Yet, the vIL-6 signal sequence targets human IL-6 secretion to nearly wild-type levels. Surprisingly, vIL-6 was not secreted from a cell line that does not express gp130 but expression of human gp130 in these cells enabled the secretion of vIL-6. Consistent with this observation, complete maturation of gp130N-glycans is inhibited by vIL-6 coexpression, suggesting that the binding of the receptor to vIL-6 occurs intracellularly in early or pre-Golgi compartments. Furthermore, a vIL-6 mutant containing an endoplasmic reticulum retention signal is not secreted but does still induce receptor activation and signaling. Secreted vIL-6 is completely glycosylated at both possibleN-glycosylaton sites and contains a large proportion of immature high-mannose glycans that is not typical of cytokines. These findings suggest that vIL-6 may induce gp130 signaling by an exclusively autocrine mechanism that relies on intracellular binding to its receptor. During KSHV infection, vIL-6 may only induce signaling in KSHV-infected cells to benefit the viral life cycle and promote oncogenic transformation.

scholarly journals The Human Cytomegalovirus UL112-113 Locus Can Activate the Full Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication Cycle

2009 ◽  
Vol 83 (9) ◽  
pp. 4695-4699 ◽  
Author(s):  
Richard Wells ◽  
Laurence Stensland ◽  
Jeffrey Vieira
Keyword(s):  
Human Cytomegalovirus ◽  
Kaposi's Sarcoma ◽  
Hcmv Infection ◽  
Infectious Virus ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Lytic Cycle ◽  
A Cell ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Human cytomegalovirus (HCMV) infection of a cell containing latent Kaposi's sarcoma-associated herpesvirus (KSHV) results in the activation of KSHV lytic replication and the production of infectious virus. In this study, we examined the HCMV genes identified as having a role in the activation of HCMV early genes for their ability to activate KSHV lytic replication. It was found that the UL112-113 locus was able to activate the complete KSHV lytic cycle, while the UL122-123 locus, encoding the IE1 and IE2 proteins, known to be strong transactivators, did not.

scholarly journals Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) in primary effusion lymphoma: ultrastructural demonstration of herpesvirus in lymphoma cells

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 4937-4943 ◽  
Author(s):  
W Said ◽  
K Chien ◽  
S Takeuchi ◽  
T Tasaka ◽  
H Asou ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Body Cavity ◽  
Molecular Evidence ◽  
A Cell ◽  
Malignant Effusions ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Recent molecular evidence suggests an association with a new herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), and primary effusion lymphomas (PELs). PELs have a characteristic morphology, phenotype, and clinical presentation, with malignant effusions in the absence of a contiguous solid tumor mass. We have established a cell line (KS-1) from a KSHV-positive human immunodeficiency virus (HIV)-negative patient with pleural cavity-based lymphoma that was passaged into triple-immunodeficient BNX mice. In contrast to cell lines from body cavity-based lymphomas derived from HIV-positive individuals that contain both KSHV and Epstein Barr viral genome, these cells contain only KSHV, allowing for uncontaminated virologic studies. Ultrastructural examination identified malignant cells with features of late differentiating B cells (immunoblasts). Cells with viral cytopathic effect contained typical 110-nm intranuclear herpesvirus nucleocapsids and complete cytoplasmic virions, confirming the association of PEL with KSHV.

scholarly journals Antiviral effect of Alloferon on Kaposi's sarcoma‐associated herpesvirus

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Na Eun Lee ◽  
Jae Seung Kang ◽  
Jee Eun Kim ◽  
Da Jung Jung ◽  
Seung Koo Lee ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Antiviral Effect ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus
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