KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine

Ganem, Don

doi:10.1172/jci40567

Cited by 341 publications

(406 citation statements)

References 188 publications

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“…In addition, systemic ganciclovir treatment of AIDS patients reduced the incidence of Kaposi's sarcoma during the follow-up period (25). These observations suggest that lytic replication is also important for viral persistence and, in the case of HHV-8, for Kaposi's sarcoma progression (17). Though our observations show that latency is the predominant mode of AlHV-1 infection during WD-MCF, the role of lytic AlHV-1 replication in WD-MCF remains unknown.…”

Section: Discussionmentioning

confidence: 91%

Ex Vivo Bioluminescence Detection of Alcelaphine Herpesvirus 1 Infection during Malignant Catarrhal Fever

Dewals

Myster

Palmeira

et al. 2011

J Virol

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Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be reproduced in rabbits. WD-MCF is described as a combination of lymphoproliferation and degenerative lesions in virtually all organs and is caused by unknown mechanisms. Recently, we demonstrated that WD-MCF is associated with the proliferation of CD8 ؉ cells supporting a latent type of infection in lymphoid tissues. Here, we investigated the macroscopic distribution of AlHV-1 infection using ex vivo bioluminescence imaging in rabbit to determine whether it correlates with the distribution of lesions in lymphoid and nonlymphoid organs. To reach that goal, a recombinant AlHV-1 strain was produced by insertion of a luciferase expression cassette (luc) in an intergenic region. In vitro, the reconstituted AlHV-1 luc ؉ strain replicated comparably to the parental strain, and luciferase activity was detected by bioluminescence imaging. In vivo, rabbits infected with the AlHV-1 luc ؉ strain developed WD-MCF comparably to rabbits infected with the parental wild-type strain, with hyperthermia and increases of both CD8 ؉ T cell frequencies and viral genomic charge over time in peripheral blood mononuclear cells and in lymph nodes at time of euthanasia. Bioluminescent imaging revealed that AlHV-1 infection could be detected ex vivo in lymphoid organs but also in lung, liver, and kidney during WD-MCF, demonstrating that AlHV-1 infection is prevalent in tissue lesions. Finally, we show that the infiltrating mononuclear leukocytes in nonlymphoid organs are mainly CD8 ؉ T cells and that latency is predominant during WD-MCF.

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Section: Discussionmentioning

confidence: 91%

Ex Vivo Bioluminescence Detection of Alcelaphine Herpesvirus 1 Infection during Malignant Catarrhal Fever

Dewals

Myster

Palmeira

et al. 2011

J Virol

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“…To spread within an individual or to new hosts, the virus must periodically reactivate to enter a lytic cycle, during which most viral genes are expressed, resulting in the production of infectious progeny and ultimately cell death. Despite its cell-destructive nature, the lytic cycle is believed to play key roles in the development of KSHV malignancies (Ganem 2010). The study of host responses to KSHV lytic replication is therefore crucial for understanding KSHV pathogenesis.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

The spring-loaded genome: Nucleosome redistributions are widespread, transient, and DNA-directed

et al. 2013

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Nucleosome occupancy plays a key role in regulating access to eukaryotic genomes. Although various chromatin regulatory complexes are known to regulate nucleosome occupancy, the role of DNA sequence in this regulation remains unclear, particularly in mammals. To address this problem, we measured nucleosome distribution at high temporal resolution in human cells at hundreds of genes during the reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV). We show that nucleosome redistribution peaks at 24 h post-KSHV reactivation and that the nucleosomal redistributions are widespread and transient. To clarify the role of DNA sequence in these nucleosomal redistributions, we compared the genes with altered nucleosome distribution to a sequence-based computer model and in vitro-assembled nucleosomes. We demonstrate that both the predicted model and the assembled nucleosome distributions are concordant with the majority of nucleosome redistributions at 24 h post-KSHV reactivation. We suggest a model in which loci are held in an unfavorable chromatin architecture and ''spring'' to a transient intermediate state directed by DNA sequence information. We propose that DNA sequence plays a more considerable role in the regulation of nucleosome positions than was previously appreciated. The surprising findings that nucleosome redistributions are widespread, transient, and DNA-directed shift the current perspective regarding regulation of nucleosome distribution in humans.

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“…The multidrug antiretroviral regimens intervention based on a combination of reverse transcriptase and PIs have improved the clinical outcome of HIV-1 infection indicated by an important decline in AIDS incidence and mortality, but, on the other hand, they almost contribute to the oxidative metabolism which adds risk of molecular damage and replication of diverse virus contributing to polyp pathology condition [2,48,49]. These findings could be explained in part by several mechanisms such as low intake of antioxidants or their precursors, malabsorption and, in peripheral tissue, enhanced cysteine metabolism with a consequent loss of sulfur group which may account for GSH and antioxidant deficiency during HIV infection which persists after antiretroviral therapy [14,15,50,51]. Considering those aspects the exploration of redox status before antiretroviral therapy is encouraged in different conditions.…”

Section: Discussionmentioning

confidence: 99%

Multivariate discriminant analysis of redox and progression indexes in Cuban AIDS patients with Kaposis sarcoma

Valle¹,

Duque-Vizcaino²,

Calás-Hechavarria³

et al. 2017

Oxid Antioxid Med Sci

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Objectives: Infection by human immunodeficiency virus (HIV) generates sustained reactive oxygen species production. An increasing number of studies underline the pathogenic impact of high-grade local and systemic oxidative stress in the activation of Herpesvirus 8 producing Kaposi's sarcoma (KS) co-infection in acquired immunodeficiency syndrome (AIDS) patients. This study aimed to determine the redox status in AIDS-KS Cuban individuals and to explore the relation between redox and progression variables. Methods: Blood samples were drawn from 99 individuals divided into three groups (33 each one; age range 30-50 years): AIDS, AIDS-KS, and presumable healthy subjects. Total peroxide, malondialdehyde, and advanced oxidation protein products as damage indexes and antioxidant responses (glutathione, peroxidation potential, superoxide dismutase, and catalase) were determined from the blood samples. Furthermore, hematological and hemochemical indexes, progression indexes (viral load, CD4 + T lymphocyte absolute count), and tumoral progression indexes were assessed. Different statistical analyses were done. Results: Compared to healthy subjects, both groups of AIDS patients had significant differences in global indices of damage and antioxidant status. The comparison between the groups revealed that AIDS-KS group had a significantly higher damage and lower antioxidant status compared to the healthy control and AIDS groups. Multivariate statistical analysis clearly separated groups according progression indexes and redox profile, obtaining two canonical functions. Conclusions: These results corroborate that substantial oxidative stress occurs in AIDS condition and also during KS-HIV co-infection with different molecular extension and interdependence to progression indexes. Redox indexes diagnosis should be considered in early diagnostics, prevention and treatment of KS-HIV coinfection, which would be worthwhile to conduct a more comprehensive study and manage of infection.

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KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine

Cited by 341 publications

References 188 publications

Ex Vivo Bioluminescence Detection of Alcelaphine Herpesvirus 1 Infection during Malignant Catarrhal Fever

Ex Vivo Bioluminescence Detection of Alcelaphine Herpesvirus 1 Infection during Malignant Catarrhal Fever

The spring-loaded genome: Nucleosome redistributions are widespread, transient, and DNA-directed

Multivariate discriminant analysis of redox and progression indexes in Cuban AIDS patients with Kaposis sarcoma

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