Human Herpesvirus 8 Serological Markers and Viral Load in Patients with AIDS-Associated Kaposi's Sarcoma in Central African Republic

Duprez, Renan; Kassa-Kelembho, Eric; Plancoulaine, Sabine; Brière, Josette; Fossi, Mireille; Kobangue, Léon; Minsart, Pierre; Huerre, Michel; Gessain, Antoine

doi:10.1128/jcm.43.9.4840-4843.2005

Cited by 33 publications

(31 citation statements)

References 28 publications

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“…Specifically, HHV8 DNA was detected in peripheral blood of 82% of patients from Central African Republic [21], in 72% of patients from Zimbabwe (72%) [5] and is detected in ∼60% of patients from Europe or the U.S. [3,6,18,22], as compared to 93% in our patients. Differences in the frequency of detection may be due to chance, KS burden, variation in assay sensitivity, input DNA, or virus load per infected cell [16].…”

Section: Discussionmentioning

confidence: 87%

Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions

et al. 2008

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Section: Discussionmentioning

confidence: 87%

Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions

et al. 2008

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“…However, a small subset of KS tumor cells also undergo spontaneous viral lytic replication, which might contribute to KS development (51). In patients, KSHV lytic activity and the viral load are strongly correlated with the progression of KS tumors (74)(75)(76)(77). Our results suggest that the MSK1/2-CREB1 pathway might be a potential target for inhibiting KSHV lytic replication.…”

Section: Figmentioning

confidence: 80%

Screening of the Human Kinome Identifies MSK1/2-CREB1 as an Essential Pathway Mediating Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication during Primary Infection

Cheng

Sawant

Lan

et al. 2015

J Virol

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Viruses often hijack cellular pathways to facilitate infection and replication. Kaposi's sarcoma-associated herpesvirus (KSHV) is IMPORTANCEKaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus associated with several cancers. Through genome-wide kinase screening, we found that KSHV activates the MSK1/2-CREB1 pathway during primary infection and that it depends on this pathway for viral lytic replication. Inhibition of this pathway blocks KSHV lytic replication. These results illustrate a mechanism by which KSHV hijacks a cellular pathway for its replication, and they identify a potential therapeutic target. V iruses depend on cell signaling pathways for successful infection and replication. Identification of pathways hijacked by viruses not only reveals the mechanisms of infection and replication of these viruses but also provides novel therapeutic targets. Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus etiologically associated with Kaposi's sarcoma (KS), a vascular tumor of endothelial cells commonly found in AIDS patients, and with two B-cell lymphoproliferative diseases, namely, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD) (1-3). The early phase of primary KSHV infection is a highly regulated multistep event consisting of virion attachment and binding, membrane fusion, internalization, intracellular trafficking, and early viral gene expression (4). KSHV infection induces phosphorylation of cellular proteins, leading to the activation of signal transduction pathways. A number of these pathways regulate KSHV entry, trafficking, and viral gene expression (4). Binding of KSHV glycoproteins to cellular receptors activates focal adhesion kinase (FAK), Src, phosphatidylinositol-3-kinases (PI3Ks), and mitogen-activated protein kinases (MAPKs), including MEK/extracellular signal-regulated kinase (MEK/ERK), p38, and Jun N-terminal kinase (JNK), facilitating KSHV internalization and trafficking (5-10). This process depends on rearrangements of the actin and microtubule cytoskeletons and on factors, such as Rho-GTPases and diaphanous-2 (Dia-2), that regulate their dynamics (8, 11). KSHV entry and trafficking rely on the dynamics of the ubiquitin/proteasome system and on activation of the E3 ligase c-Cbl to maintain the endosomal activities and cellular signaling (12, 13).Successful KSHV infection requires the coordinated expres-

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“…Importantly, KSHV-infected cultures usually exhibit spontaneous lytic replication, where 1 to 5% of cells have entered the lytic gene cascade (39). Assays on pooled samples, such as DNA array, quantitative real-time PCR, and immunoblots, by default, include both latent and lytic subpopulations, thereby obscuring experimental analyses (8,17,32,43). Since gene expression in lytically infected cells is robust and involves a wide range of genes, the coexistence of the two states of infection precludes a precise characterization of the viral transcriptomes (latent and lytic).…”

mentioning

confidence: 99%

Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection

Adang

Parsons

Kedes

2006

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus-8) is frequently tumorigenic in immunocompromised patients. The average intracellular viral copy number within infected cells, however, varies markedly by tumor type. Since the KSHV-encoded latency-associated nuclear antigen (LANA) tethers viral episomes to host heterochromatin and displays a punctate pattern by fluorescence microscopy, we investigated whether accurate quantification of individual LANA dots is predictive of intracellular viral genome load. Using a novel technology that integrates single-cell imaging with flow cytometry, we found that both the number and the summed immunofluorescence of individual LANA dots are directly proportional to the amount of intracellular viral DNA. Moreover, combining viral (immediate early lytic replication and transcription activator [RTA] and late lytic K8.1) and cellular (syndecan-1) staining with image-based flow cytometry, we were also able to rapidly and simultaneously distinguish among cells supporting latent, immediate early lytic, early lytic, late lytic, and a potential fourth "delayed late" category of lytic replication. Applying image-based flow cytometry to KSHV culture models, we found that de novo infection results in highly varied levels of intracellular viral load and that lytic induction of latently infected cells likewise leads to a heterogeneous population at various stages of reactivation. These findings additionally underscore the potential advantages of studying KSHV biology with high-throughput analysis of individual cells.

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Human Herpesvirus 8 Serological Markers and Viral Load in Patients with AIDS-Associated Kaposi's Sarcoma in Central African Republic

Cited by 33 publications

References 28 publications

Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions

Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions

Screening of the Human Kinome Identifies MSK1/2-CREB1 as an Essential Pathway Mediating Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication during Primary Infection

Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection

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