Hidden reservoirs

Abstract

EMT-switched tumour cells that had reached the lung. Analysis of the genes being expressed in these cells correlated this resistance with increased expression of genes encoding drugmetabolizing enzymes and drug-transporter proteins. These findings were mirrored in Zheng and colleagues' Snail-or Twist-deleted pancreatic cancers, in which tumour cells with epithelial characteristics expressed higher levels of nucleoside-transporter proteins than did mesenchymal cells, potentially rendering the epithelial cells more sensitive to the chemotherapeutic drug gemcitabine. These findings challenge the prevailing hypothesis that EMT is a key element in the metastatic dissemination of epithelial cancers, and they point to a distinct role of this cell-fate transition in enhancing cancer-cell survival during drug treatment. How can these data be reconciled with compelling previous reports on the role of EMT in metastasis? The earlier work studied the effects of EMT induced by the growth factor TGFβ or by overexpression of transcriptional regulators such as Snail or Twist. Such approaches might not capture the physiological process that occurs spontaneously in cancer cells as accurately as do the methods used in the current studies. It is probable that the induction of EMT that occurs during the natural progression of a cancer may be more subtle than the full EMT switch that is induced by the expression of powerful regulators and that has been associated with high levels of metastasis. However, the limitations of the models used by Fischer et al. and Zheng et al. need to be considered before EMT-mediated tumour invasion can be dismissed outright. EMT is orchestrated by complex circuitry involving multiple signalling molecules and transcription factors. Tracing switched cells on the basis of expression of a single gene may therefore not fully capture these complicated features. Similarly, Snail and Twist function redundantly in many settings 2,7,8 , and inactivation of both (and potentially of other transcriptional regulators) simultaneously, rather than individually, may Primary tumour Distant organ Epithelial tumour cell Epithelial cell after MET Metastasis Mesenchymal cell after EMT Blood vessel Chemotherapy This article was published online on 11 November 2015. EBOLA Hidden reservoirs West Africa's Ebola epidemic continues to reveal surprises. Although the animal species that originally passed the virus to people remains a mystery, a virus reservoir and persistent disease have been identified in some human survivors.

Within host RNA virus persistence: mechanisms and consequences

“…Even such obviously acute virus infections such as Zika virus and Ebola virus in humans can persist in very small numbers of individuals over a period of months, and perhaps years, and such persistently infected individuals can occasionally transmit the virus, thereby being a potential source of future outbreaks [14,15]. Whilst no one would suggest that the ability of Ebola virus to establish persistent infections has evolved in humans, the fact that even small numbers of individuals can become persistently infected may reflect its intrinsic ability to establish persistence in its natural host.…”

“…Indeed, the CNS, as an immunologically privileged site (see below), is an organ in which RNA viruses can often establish persistent infections with disease consequences [5,19]. Recent examples include reactivation of CNS infection after apparent recovery from Ebola virus disease [14,20]. Other chronic human diseases have also been linked to persistent RNA virus infections, some controversially, include Paget's bone disease, multiple sclerosis, otosclerosis, postpolio syndrome and other late neurodegenerative diseases, chronic fatigue syndrome, certain autoimmune diseases and exacerbation of chronic obstructive pulmonary disease.…”

On the Regularities of the Polar Profiles of Proteins Related to Ebola Virus Infection and their Functional Domains

“…In 1976, the first outbreak of Ebola was formally declared in the North of Zaire (now the Democratic Republic of Congo) [1]. Since then, there have been 35 outbreaks, 25 occurring in the African continent [2] and most of them located between the tropics of Cancer and Capricorn [3]. The last outbreak reported was in 2014, with the number of fatalities and economic losses surpassing the previous 34 outbreaks altogether [2].…”

Spatiotemporal Fluctuations and Triggers of Ebola Virus Spillover

“…Notable for its unprecedented size and geographic extent, the 2013–2015 West Africa Ebola epidemic was also the first major human Ebola outbreak outside central Africa and underscored the need for improved methods to forecast emergence in novel regions. Because the natural reservoir of the Ebola virus has not been identified ( 3 ) and spillovers present an irregular pattern ( 4 , 5 ), it remains unclear how the probability of Ebola virus disease (EVD) in human populations varies in space and time. Particularly, whether EVD follows a seasonal pattern ( 6 , 7 ) and which historically unaffected geographic regions may also be at risk for EVD outbreaks ( 8 ) are 2 important questions that remain largely unanswered.…”