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Afsar R Naqvi, Alexandra Seal, Jennifer Shango, Maria Brambila Navarette, Gloria Martinez, Gabriela Chapa, Shirin Hasan, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla, Salvador Nares
MicroRNAs (miRNAs) are small, non-coding RNAs of ~18-25 nucleotides that have gained extensive attention as critical regulators in complex gene networks including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and function. Many viruses encode miRNAs that directly downregulate the expression of factors of the innate immune system, which includes proteins involved in promoting apoptosis and recruitment. In this study, we examined the expression profiles of three previously identified viral miRNAs (v-miRs) from the human herpesvirus (HHV) family, HSV-1 (miR-H1), KSHV (miR-K12-3-3p), and HCMV (miR-US4) in healthy and diseased periodontal tissues and observed increased levels of v-miRs in diseased tissues...
March 14, 2018: Biochimica et Biophysica Acta
Dimitri Topalis, Sarah Gillemot, Robert Snoeck, Graciela Andrei
Herpesviruses thymidine kinase (TK) and protein kinase (PK) allow the activation of nucleoside analogues used in anti-herpesvirus treatments. Mutations emerging in these two genes often lead to emergence of drug-resistant strains responsible for life-threatening diseases in immunocompromised populations. In this review, we analyze the binding of different nucleoside analogues to the TK active site of the three α-herpesviruses [Herpes Simplex Virus 1 and 2 (HSV-1 and HSV-2) and Varicella-Zoster Virus (VZV)] and present the impact of known mutations on the structure of the viral TKs...
March 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Alessia Gallo, Monica Miele, Ester Badami, Pier Giulio Conaldi
Patients following solid organ transplantation show a higher risk of developing cancer compared to the general population. Elevated risk is likely due to the interplay of a combination of factors, such as chronic inflammation, coexisting medical conditions, immunosuppressive regimen and persistent infection with oncogenic viruses. In addition, the tumor microenvironment plays a pivotal role in cancer progression, by driving recruitment and in situ differentiation of anti-inflammatory cells of the adaptive and innate immune system such as regulatory T cells, Th17, Dendritic Cells, Myeloid Derived Suppressor Cells, Type 2 Macrophages...
February 16, 2018: Cellular Immunology
Tate Tabtieng, Alexei Degterev, Marta M Gaglia
An important component of lytic infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is the ability of the virus to evade the innate immune response, specifically type I interferon (IFN) responses that are triggered by recognition of viral nucleic acids. Inhibition of type I IFN responses by the virus promotes viral replication. Here we report that KSHV uses a caspase-dependent mechanism to block type I IFN, in particular IFNβ, responses during lytic infection. Inhibition of caspases during KSHV reactivation resulted in increased TBK1/IKKϵ-dependent phosphorylation of IRF3 as well as elevated levels of IFNβ transcription and secretion...
March 7, 2018: Journal of Virology
M D Cyrus Oster, M D Theodore Stein, M D Sumire Kitahara, M D Serhan Alkan, Qin Huang
Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity usually characterized by presentation as a lymphomatous body cavity effusion in the absence of solid tumor mass or dissemination during its clinical course. PEL can also rarely occur as a solid lymphoma involving nodal and extranodal sites and is referred to as extracavitary PEL. Here we report a unique case of extracavitary PEL in a 49year-old HIV-seropositive patient, who presented with vague abdominal pain and 20 pound weight loss. Esophagogastroduodenoscopy and colonoscopy revealed >100 broad based intestinal polyps ranging from 2 mm to 3cm in size, spreading from the duodenum to the rectum as a typical impression of "intestinal polyposis syndrome"...
March 2, 2018: Human Pathology
Kendra A Bussey, Ulrike Lau, Sophie Schumann, Antonio Gallo, Lisa Osbelt, Markus Stempel, Christine Arnold, Josef Wissing, Hans Henrik Gad, Rune Hartmann, Wolfram Brune, Lothar Jänsch, Adrian Whitehouse, Melanie M Brinkmann
Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few oncogenic human viruses known to date. Its large genome encodes more than 85 proteins and includes both unique viral proteins as well as proteins conserved amongst herpesviruses. KSHV ORF20 is a member of the herpesviral core UL24 family, but the function of ORF20 and its role in the viral life cycle is not well understood. ORF20 encodes three largely uncharacterized isoforms, which we found were localized predominantly in the nuclei and nucleoli...
March 2, 2018: PLoS Pathogens
Christian Münz
The human γ-herpesviruses Epstein-Barr virus (EBV or HHV4) and Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) are each associated with around 2% of all tumors in humans worldwide. However, investigations into their infection, oncogenesis, and immune responses that protect from the associated tumors have been hampered by the exclusive tropism of these pathogens for humans. Mice with reconstituted human immune system components (HIS mice) provide the unique opportunity to study persistent infection, virus associated lymphoma formation, and cell-mediated immune control of EBV and KSHV...
2018: Frontiers in Immunology
Xiujuan Wu, Zongfeng Zhao, Yuan Ding, Fang Xiang, Xiaojing Kang, Xiongming Pu
In this study, we investigated the expression of microRNAs (miRNAs) in the skin samples from the Han and Uyghur populations in Xinjiang, China. The miRNA levels of the normal skin samples from 10 individuals of Uyghur or Han were tested by microarray and the expression differentiations were compared. Among the 3100 probes for microarray, a total of 247 miRNAs were differentially expressed in the Han versus Uyghur population, including 76 upregulated miRNAs and 171 downregulated miRNAs. The most significantly upregulated miRNAs were miR-141-3p, miR-1915-5p, kshv-miR-K12-2-5p, and miR-222-3p...
February 2018: Medicine (Baltimore)
Christopher P Chen, Frank Chuang, Yoshihiro Izumiya
It is well known that spatial and temporal regulation of genes is an integral part of governing proper gene expression. Consequently, it is invaluable to understand where and when transcription is taking place within nuclear space and to visualize the relationship between episomes infected within the same cell's nucleus. Here, both immunofluorescence (IFA) and RNA-FISH have been combinedto identify actively transcribing Kaposi's sarcoma-associated herpesvirus (KSHV) episomes. By staining KSHV latency-associated nuclear antigen (LANA), it is possible to locate where viral episomes exist within the nucleus...
January 18, 2018: Journal of Visualized Experiments: JoVE
Seho Cha, Myung-Suk Kang, Taegun Seo
Viral factors interact with host cellular proteins, leading to dysregulation of signaling pathways. The Wnt pathway is known to participate in embryonic development and oncogenesis under dysregulation conditions. A downstream factor of the Wnt signaling pathway, β-catenin, activates T-cell factor (TCF)-dependent transcription, which contributes to cell proliferation and tumorigenesis. In this study, we demonstrated that viral protein kinase (vPK) encoded by Kaposi's sarcoma-associated herpesvirus inhibits the Wnt signaling pathway without affecting nuclear localization and expression of β-catenin...
February 26, 2018: Biochemical and Biophysical Research Communications
Anna K Großkopf, Armin Ensser, Frank Neipel, Doris Jungnickl, Sarah Schlagowski, Ronald C Desrosiers, Alexander S Hahn
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus associated with Kaposi's sarcoma and two B-cell malignancies. The rhesus monkey rhadinovirus (RRV) is a virus of nonhuman primates that is closely related to KSHV. Eph family receptor tyrosine kinases (Ephs) are cellular receptors for the gH/gL glycoprotein complexes of both KSHV and RRV. Through sequence analysis and mutational screens, we identified conserved residues in the N-terminal domain of KSHV and RRV glycoprotein H that are critical for Eph-binding in vitro...
February 2018: PLoS Pathogens
Minako Ikoma, Soren Gantt, Corey Casper, Yuko Ogata, Qing Zhang, Ryan Basom, Michael R Dyen, Timothy M Rose, Serge Barcy
Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). Both KSHV and HIV infections are endemic in Uganda, where KS is among the most common cancers in HIV-infected individuals. Recent studies examined the use of small RNAs as biomarkers of disease, including microRNAs (miRNAs), with viral and tumor-derived miRNAs being detected in exosomes from individuals with KSHV-associated malignancies. In the current study, the host and viral extracellular mature miRNA expression profiles were analyzed in blood of KS-negative individuals in Uganda, comparing those with or without KSHV detectable from the oropharynx...
2018: PloS One
Suhani Thakker, Roxanne C Strahan, Alexandra N Scurry, Timsy Uppal, Subhash C Verma
Kaposi's sarcoma (KS) is a highly-vascularized tumor characterized by inflammation and extensive neo-angiogenesis. The KS tumor microenvironment is rich in inflammatory and pro-angiogenic cytokines. Here, we report that the expression of Epidermal growth factor-like domain 7 (EGFL7) is upregulated in Kaposi's sarcoma-associated herpes virus (KSHV) infected cells. EGFL7 is a secreted pro-angiogenic cytokine that has been implicated in angiogenesis and the proliferation of endothelial cells during many pathological conditions...
January 2, 2018: Oncotarget
H Jacques Garrigues, Laura K DeMaster, Yelena E Rubinchikova, Timothy M Rose
No abstract text is available yet for this article.
February 2018: Virology
Hye Ryun Yu, Yeong Jun Kim, Hye-Ra Lee
Primary effusion lymphoma (PEL), strongly linked with latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), constitutively expresses cellular interferon regulatory factor 4 (IRF4) while suppressing the expression of B cell lymphoma 6 (BCL6). Recently, it was shown that IRF4, a key transcriptional repressor of BCL6, might be a pivotal regulator of KSHV for balancing between latency and its reactivation in PEL cells. However, the action of the BCL6-IRF4 transcription factor axis during KSHV's life cycle is not clear...
February 19, 2018: Biochemical and Biophysical Research Communications
Lauren A Gay, Sunantha Sethuraman, Merin Thomas, Peter C Turner, Rolf Renne
KS tumors are derived from endothelial cells and express KHSV microRNAs (miRNAs). Although miRNA targets have been identified in B cell lymphoma-derived cells and in epithelial cells, little has been done to characterize the KSHV miRNA targetome in endothelial cells. A recent innovation in the identification of miRNA targetomes, Cross-linking, Ligation, and Sequencing of Hybrids (CLASH), unambiguously identifies miRNAs and their targets by ligating the two species while both are still bound within the RNA-Induced Silencing Complex (RISC)...
January 31, 2018: Journal of Virology
Henri Gruffat, Evelyne Manet
Kaposi's sarcoma human herpesvirus (KSHV) is the etiologic agent of primary effusion lymphoma (PEL) in which Epstein-Barr virus (EBV) is also very often present. By using a humanized mouse model, Pr. Münz's team has been able to demonstrate that EBV/KSHV co-infection increases KSHV persistence and cell transformation through the stimulation of EBV replication. This is the first model of PEL in small animals, opening up exciting prospects for future studies on this unique lymphoma.
January 2018: Médecine Sciences: M/S
Daphné Denis, Vannina Seta, Elodie Regnier-Rosencher, Nora Kramkimel, Johan Chanal, Marie-Françoise Avril, Nicolas Dupin
BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with KSHV (Kaposi's Sarcoma-Associated Herpesvirus). In low endemic countries, KSHV infects predominantly men having sex with men (MSM). OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors. METHODS: Retrospective single-center study of CKS cases...
January 29, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Angela Nalwoga, Wendell Miley, Nazzarena Labo, Alison Elliott, Stephen Cose, Denise Whitby, Robert Newton
We investigated associations between KSHV seroconversion age and KSHV antibody values in Ugandan children. Every annual delay in KSHV seroconversion age was associated with a reduction of 19% (p<0.0001) in K8.1 and 27% (p<0.0001) in ORF73 antibody values at age 6. Early infection may be an important risk factor for KSHV pathogenesis and viral shedding in saliva, leading to transmission.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited...
January 23, 2018: Pediatric Infectious Disease Journal
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
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