scholarly journals Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells

2011 ◽  
Vol 41 (7) ◽  
pp. 1958-1968 ◽  
Author(s):  
Nick C. Matthews ◽  
Martin R. Goodier ◽  
Rebecca C. Robey ◽  
Mark Bower ◽  
Frances M. Gotch
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Kaposi's Sarcoma ◽  
Latent Infection ◽  
Kaposi’S Sarcoma ◽  
Killer Cells ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

scholarly journals Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

2011 ◽  
Vol 2011 ◽  
pp. 1-19 ◽  
Author(s):  
Fengchun Ye ◽  
Xiufen Lei ◽  
Shou-Jiang Gao
Keyword(s):  
Kaposi's Sarcoma ◽  
Latent Infection ◽  
De Novo ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Stromal Microenvironment ◽  
Wide Range ◽  
Cellular Pathways ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV) consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resultingde novoinfection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS). The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

scholarly journals Host Range of Kaposi's Sarcoma-Associated Herpesvirus in Cultured Cells

2003 ◽  
Vol 77 (11) ◽  
pp. 6474-6481 ◽  
Author(s):  
Jill T. Bechtel ◽  
Yuying Liang ◽  
Joshua Hvidding ◽  
Don Ganem
Keyword(s):  
Host Range ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Latent Infection ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Serial Transfer ◽  
Latently Infected ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Difficulties in efficiently propagating Kaposi's sarcoma-associated herpesvirus (KSHV) in culture have generated the impression that the virus displays a narrow host range. Here we show that, contrary to expectation, KSHV can establish latent infection in many adherent cell lines, including human and nonhuman cells of epithelial, endothelial, and mesenchymal origin. (Paradoxically, the only lines in which we have not observed successful latent infection are cultured lymphoma cell lines.) In most latently infected lines, spontaneous lytic replication is rare and (with only two exceptions) is not efficiently induced by phorbol ester treatment—a result that explains the failure of most earlier studies to observe efficient serial transfer of infection. However, ectopic expression of the KSHV lytic switch protein RTA from an adenoviral vector leads to the prompt induction of lytic replication in all latently infected lines, with the production of infectious KSHV virions. These results indicate (i) that the host cell receptor(s) and entry machinery for KSHV are widely distributed on cultured adherent cells, (ii) that latency is the default pathway of infection, and (iii) that blocks to lytic induction are frequent and largely reside at or upstream of the expression of KSHV RTA.

scholarly journals Involvement of SSRP1 in Latent Replication of Kaposi's Sarcoma-Associated Herpesvirus

2009 ◽  
Vol 83 (21) ◽  
pp. 11051-11063 ◽  
Author(s):  
Jianhong Hu ◽  
Eugene Liu ◽  
Rolf Renne
Keyword(s):  
Dna Replication ◽  
Kaposi's Sarcoma ◽  
Latent Infection ◽  
Mutational Analysis ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Dominant Negative ◽  
Nuclear Antigen ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (also named human herpesvirus 8) is a γ-herpesvirus that undergoes both lytic and latent infection. During latent infection, two viral elements are required: latency-associated nuclear antigen (LANA), which functions as an origin binding protein, and the latent origin, which resides within the terminal repeats (TRs) of the viral genome. Previously, we identified two cis-elements within the TRs which are required for latent DNA replication: two LANA binding sites (LBS1 and LBS2 [LBS1/2]) and a GC-rich replication element (RE) upstream of LBS1/2. To further characterize the RE, we constructed a 71-bp minimal replicon (MR) and performed a detailed mutational analysis. Our data indicate that the first 8 nucleotides within the RE are critical for replication. Moreover, both the position and the distance between the RE and LBS1/2 can affect origin replication activity, suggesting that the RE may function as a loading pad for cellular proteins involved in replication. Using biotinylated DNA fragments of wild-type or mutant MRs as probes, we identified 30 proteins that preferentially bind to the origin. Among these proteins, structure-specific recognition protein 1 (SSRP1), a subunit of the FACT complex, and telomeric repeat binding factor 2 (TRF2) formed complexes with LANA at the MR region. Furthermore, the small interfering RNA-based knockdown of SSRP1, but not the dominant-negative-based knockdown of TRF2, significantly decreased the efficiency of LANA-dependent DNA replication. These results indicate that SSRP1 is a novel cellular protein involved in LANA-dependent DNA replication.

302 INHIBITION OF HUMAN NATURAL KILLER (NK) CELL-MEDIATED CYTOTOXICITY IN MINIPIG CELLS BY KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS K5 PROTEIN

2008 ◽  
Vol 20 (1) ◽  
pp. 231
Author(s):  
G. S. Han ◽  
K. M. Choi ◽  
S. P. Hong ◽  
J. Y. Yoo ◽  
E. J. Kim ◽  
...  
Keyword(s):  
Natural Killer ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Cell Activation ◽  
Nk Cell ◽  
Kaposi’S Sarcoma ◽  
Xenograft Rejection ◽  
Fetal Fibroblasts ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Human natural killer (NK) cell-mediated response plays an important role in xenograft rejection. In the case of pig-to-human xenotransplantation, it has been suggested that NK cells are involved in delayed-type rejection, which is characterized by pig endothelial cell activation, direct lysis, and secretion of proinflammatory cytokines. Natural killer cell activation can be a direct barrier to the potential use of pig organs for human xenograft transplantation. Therefore, it is important to suppress NK cell activity on pig-to-human xenografts. Expression of Kaposi's sarcoma-associated herpesvirus (KSHV)-K5 molecules inhibits the cytotoxic activity of NK-activating receptor (B7-2, ICAM-1). As a consequence, K5 expression drastically inhibits NK cell-mediated cytotoxicity. In this study, we produced cell lines expressing K5 to control NK-mediated cytotoxicity in minipig cells. We transfected the K5 gene into minipig fetal fibroblasts and established 2 transgenic clonal cell lines. Presence of the K5 gene was confirmed by PCR, and expression of the gene was identified by real-time PCR and flow cytometry. In an NK cytotoxicity assay, the rate of NK-92MI-mediated cytotoxicity was significantly reduced, to 48.4 � 5.9% compared with the control (75.6 � 5.8%; P < 0.05, n = 8, paired t-testing). In conclusion, these results indicate that the expression of K5 molecules on porcine cells can efficiently control NK-mediated cytotoxicity. This strategy can be used in transgenic pig production in which porcine organs would be protected from NK-mediated rejection.

scholarly journals RNAs in the Virion of Kaposi's Sarcoma-Associated Herpesvirus

2005 ◽  
Vol 79 (16) ◽  
pp. 10138-10146 ◽  
Author(s):  
Jill Bechtel ◽  
Adam Grundhoff ◽  
Don Ganem
Keyword(s):  
Kaposi's Sarcoma ◽  
Latent Infection ◽  
Cultured Cells ◽  
De Novo ◽  
Kaposi’S Sarcoma ◽  
Northern Blotting ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT De novo infection of cultured cells with Kaposi's sarcoma-associated herpesvirus (KSHV) typically results in a latent infection. Recently, however, it has been reported that a subset of lytic mRNAs can be detected in cells shortly after KSHV infection; this expression is transient and eventually subsides, leading to latent infection (H. H. Krishnan et al., J. Virol 78:3601-3620, 2004). Since it has been shown that viral RNAs can be packaged into other herpesvirus virions, we sought to determine if KSHV virions contained RNAs and, if so, whether these RNAs contributed to the pool of lytic transcripts detected immediately after infection. Using DNA microarray, reverse transcription (RT)-PCR, and Northern blotting analyses, we identified 11 virally encoded RNAs in KSHV virions. These corresponded in size to the full-length mRNAs found in cytoplasmic RNA, and at least one was directly demonstrated to be translated upon infection in the presence of actinomycin D. Ten of these RNAs correspond to transcripts reported by Krishnan et al. at early times of infection, representing ca. 30% of such RNAs. Thus, import of RNAs in virions can account for some but not all of the early-appearing lytic transcripts. Quantitative RT-PCR analysis of infected-cell RNA demonstrated that most of the virion RNAs were very abundant at late times of infection, consistent with nonspecific incorporation during budding. However, the intracellular levels of one virion mRNA, encoding the viral protease, were much lower than those of transcripts not packaged in the virus particle, strongly suggesting that it may be incorporated by a specific mechanism.

scholarly journals Comprehensive Mapping and Analysis of Kaposi's Sarcoma-Associated Herpesvirus 3′ UTRs Identify Differential Posttranscriptional Control of Gene Expression in Lytic versus Latent Infection

2013 ◽  
Vol 87 (23) ◽  
pp. 12838-12849 ◽  
Author(s):  
Lydia V. McClure ◽  
Rodney P. Kincaid ◽  
James M. Burke ◽  
Adam Grundhoff ◽  
Christopher S. Sullivan
Keyword(s):  
Gene Expression ◽  
Kaposi's Sarcoma ◽  
Latent Infection ◽  
Regulation Of Gene Expression ◽  
Gc Content ◽  
Kaposi’S Sarcoma ◽  
Lytic Infection ◽  
Control Of Gene Expression ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

3′ untranslated regions (UTRs) are known to play an important role in posttranscriptional regulation of gene expression. Here we map the 3′ UTRs of Kaposi's sarcoma-associated herpesvirus (KSHV) using next-generation RNA sequencing, 3′ rapid amplification of cDNA ends (RACE), and tiled microarray analyses. Chimeric reporters containing the KSHV 3′ UTRs show a general trend toward reduced gene expression under conditions of latent infection. Those 3′ UTRs with a higher GC content are more likely to be associated with reduced gene expression. KSHV transcripts display an extensive use of shared polyadenylation sites allowing for partially overlapping 3′ UTRs and regulatory activities. In addition, a subset of KSHV 3′ UTRs is sufficient to convey increased gene expression under conditions of lytic infection. These results suggest a role for viral 3′ UTRs in contributing to differential gene expression during latent versus lytic infection.

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