The successful replication of mammalian DNA viruses requires that they gain control of key cellular signalling pathways that affect broad aspects of cellular macromolecular synthesis, metabolism, growth and survival. The phosphatidylinositol 3′-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway is one such pathway. Mammalian DNA viruses have evolved various mechanisms to activate this pathway to obtain the benefits of Akt activation, including the maintenance of translation through the activation of mTOR. In addition, viruses must overcome the inhibition of this pathway that results from the activation of cellular stress responses during viral infection. This Review will discuss the range of mechanisms that mammalian DNA viruses use to activate this pathway, as well as the multiple mechanisms these viruses have evolved to circumvent inhibitory stress signalling.The successful replication of mammalian DNA viruses, such as polyomaviruses (also called papovaviruses), adenoviruses, herpesviruses and poxviruses, requires viral adaptation of the host cell to establish an environment that can accommodate the increased demands for nutrients, energy and macromolecular synthesis that accompany viral infection. All DNA viruses must gain control of key cellular signalling pathways that affect broad aspects of cellular macromolecular synthesis, metabolism, growth and survival. The phosphatidylinositol 3′-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway is one such pathway. Virtually all mammalian viruses, both DNA and RNA, must regulate this pathway, either by activating or inactivating some aspect of it 1 . In general, mammalian DNA viruses activate this pathway at some point in their life cycle to benefit from the growth, metabolic, anti-apoptotic and translational functions that the pathway controls. However, a viral mechanism for activating this pathway is not enough; to maintain control, viruses must also overcome the many controls that are used to inhibit this pathway when cellular stress responses are activated during viral infection.Correspondence to J.C.A., e-mail: alwine@mail.med.upenn.edu. * These authors contributed equally to this work. DATABASES NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe substantial alterations in cellular physiology that are induced by a viral lytic infectionas a result of nutrient depletion, energy depletion, hypoxia and endoplasmic reticulum stress -activate cellular stress responses that alert the cell to problems with metabolic and synthetic processes. The resulting stress signalling activates mechanisms that either alleviate the problems or, if this is not possible, induce apoptosis. Stress signalling has many effects that can be either beneficial or detrimental to viral growth. One example of a detrimental effect is inhibition of translation, which is among the most common consequences of cellular stress responses 2-6 . Although the inhibition of this energy-intensive process permits the cell to recover from stress,...

Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic shock. We summarize the mechanisms of immune dysregulation and virus-mediated cell damage in Ebola virus-infected patients. Future approaches to prevention and treatment of infection will be guided by answers to unresolved questions about interspecies transmission, molecular mechanisms of pathogenesis, and protective adaptive and innate immune responses to Ebola virus.