Detection of viral pathogens in high grade gliomas from unmapped next-generation sequencing data.

Gliomas are the most common malignant brain tumors and account for around 60% of all primary central nervous system cancers. Glioblastoma multiforme (GBM) is a grade IV glioma associated with a poor outcome despite recent advances in chemotherapy. The etiology of gliomas is unknown, but neurotropic viruses including the Epstein-Barr virus (EBV) that is transmitted via salivary and genital fluids have been implicated recently. EBV is a member of the gamma herpes simplex family of DNA viruses that is known to cause infectious mononucleosis (glandular fever) and is strongly linked with the oncogenesis of several cancers, including B-cell lymphomas, nasopharyngeal, and gastric carcinomas. The fact that EBV is thought to be the causative agent for primary central nervous system (CNS) lymphomas in immune-deficient patients has led to its investigations in other brain tumors including gliomas. Here, we provide a review of the clinical literature pertaining to EBV in gliomas and discuss the possibilities of this virus being simply associative, causative, or even an experimental artifact. We searched the PubMed/MEDLINE databases using the following key words such as: glioma(s), glioblastoma multiforme, brain tumors/cancers, EBV, and neurotropic viruses. Our literature analysis indicates conflicting results on the presence and role of EBV in gliomas. Further comprehensive studies are needed to fully implicate EBV in gliomagenesis and oncomodulation. Understanding the role of EBV and other oncoviruses in the etiology of gliomas, would likely open up new avenues for the treatment and management of these, often fatal, CNS tumors.

/pdf/epstein-barr-virus-in-gliomas-cause-association-or-artifact-4g6t1jij3f.pdf

Epstein-Barr Virus in Gliomas: Cause, Association, or Artifact?

Virome genomics: a tool for defining the human virome

Polymeric and small molecule-conjugates of temozolomide as improved therapeutic agents for glioblastoma multiforme.

Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2-specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target. 

Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma

While some avian retroviruses have been shown to induce gliomas in animal models, human herpesviruses, specifically, the most extensively studied cytomegalovirus, and the much less studied roseolovirus HHV-6, and Herpes simplex viruses 1 and 2, currently attract more and more attention as possible contributing or initiating factors in the development of human brain tumors. The aim of this review is to summarize and highlight the most provoking findings indicating a potential causative link between brain tumors, specifically malignant gliomas, and viruses in the context of the concepts of viral oncomodulation and the tumor stem cell origin.

The roles of viruses in brain tumor initiation and oncomodulation

The results of the Caribbean crisis in the domestic and foreign literature have rarely been covered from the point of view of the Soviet-Cuban relations that influenced the internationalist policy of Cuba in Africa in the 1970s. The author analyzes: the degree of independence of Cuba’s policy in Africa, the participation of the USSR in it and the fairness of accusations brought by Washington. The results of the analysis show that deploying of Cuban “volunteers” in Angola and then in Ethiopia was not initiated by the USSR, which aimed at maintaining détente in relations with the West. Moreover, new deterioration of relations with Cuba amid escalating Chinese-Soviet tensions, increasing centrifugal tendencies in the “socialist commonwealth” and emergence of “Eurocommunism” threatened to further weaken the “world system of socialism” and erode the ideological foundations of Marxism-Leninism. By analyzing Cuba’s internationalist activity in Africa, the author has been able to draw some conclusions about its implications for the international communist movement and its influence on the balance of power in the world before perestroika policy began in the Soviet Union. The end of détente policy did not allow the USSR to redirect the resources released from the arms race to improving the living conditions of the Soviet people. Cuban revolutionary activity contributed to fragmentation of the formerly united “upfront antiimperialist forces.” The weakening of the ideological foundations of “real socialism” was an additional factor that prompted the Soviet leadership, represented by Mikhail Gorbachev, to begin a policy of perestroika. Cuba’s ‘progress’ in Africa contributed to consolidation of Cuban society around the policy of the Cuban Communist Party, which, in turn, helped it to withstand the difficulties of the “peculiar period of peace” in the early 1990s.

Soviet-Cuban relations after the Caribbean crisis, the collapse of détente and lessons for the future

/pdf/40-years-after-the-war-for-the-malvinas-lessons-for-today-7lwx3tz5.pdf

40 years after the war for the Malvinas (lessons for today)

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The roles of viruses in brain tumor initiation and oncomodulation

Soviet-Cuban relations after the Caribbean crisis, the collapse of détente and lessons for the future

40 years after the war for the Malvinas (lessons for today)