Cytopathic effects: virus-modulated manifestations of innate immunity?

Agol, Vadim I.

doi:10.1016/j.tim.2012.09.003

Cited by 33 publications

(35 citation statements)

References 54 publications

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“…CPE on NPC Generally, the term CPE is attributed to diverse pathological alterations in cells triggered by eukaryotic viruses (Agol 2012). It includes the ability to injure or kill the infected cells.…”

Section: Methodsmentioning

confidence: 99%

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

et al. 2015

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Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies have demonstrated that neural precursor cells (NPCs) show the greatest susceptibility to CMV infection in the developing brain. We sought to establish an in vitro model of CMV infection of the developing brain in order to analyze the cellular events associated with invasion by this virus. To this end, we employed two cell lines as a permanent source of NPC, avoiding the continuous use of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an immortalized cell line of human fetal neural origin, hNS-1. We also investigated the effect of the differentiation stage in relation to the susceptibility of these cell lines by comparing the neuroblastoma cell line with the multipotent cell line hNS-1. We found that the effects of the virus were more severe in the neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells, hNS-1-differentiated cells were also susceptible to infection. Viability of differentiated hNS-1 cells decreased after CMV infection in contrast to undifferentiated cells. In addition, differentiated hNS-1 cells showed an extensive cytopathic effect whereas the effect was scarce in undifferentiated cells. We describe some of the effects of CMV in neural stem cells, and our observations suggest that the degree of differentiation is important in the acquisition of susceptibility.

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Section: Methodsmentioning

confidence: 99%

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

et al. 2015

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“…Cell death signals emerge from viral engagement of death receptors, signaling during uncoating, and postentry events (for reviews, see Lamkanfi and Dixit, 2010;Danthi, 2011;Agol, 2012;Kaiser et al, 2013). Innate immune responses comprise intrinsic mechanisms, which directly restrict viral replication and assembly, therefore leading to nonpermissiveness of the cell (Yan and Chen, 2012).…”

Section: Early Signaling: Mobilizing Cell Defensementioning

confidence: 99%

Innate Immunity to Adenovirus

et al. 2014

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Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and selflimiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate-adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virusassociated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features.

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“…Second, concepts of targeting innate immune deficiency may miss out on promising modes of antineoplastic efficacy. Tumor cytotoxicity, eg, the coveted “immunogenic” kind, may result from the innate defense:virus arms race rather than unilateral toxic effects of the virus or its products alone . Harming/killing of defenseless cells with a blunted innate antiviral response may lack this potentially important quality.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic polio virotherapy of cancer

Brown

Dobrikova

Dobrikov

et al. 2014

Cancer

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Recently, the century-old idea of targeting cancer with viruses (‘oncolytic viruses’) has come of age, with promise documented in early-stage and several late-stage clinical trials in a variety of cancers. While originally prized for their direct tumor cytotoxicity (‘oncolytic virotherapy’), recently, the pro-inflammatory and immunogenic effects of viral tumor infection (‘oncolytic immunotherapy’) have come into focus. Indeed, a capacity for eliciting broad, sustained anti-neoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal pro-inflammatory stimulation and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Due to fundamentally different relationships with their hosts (malignant or not), diverse replication strategies and distinct modes of tumor cytotoxicity/ killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, we highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO, and their implications for oncolytic immunotherapy in the clinic.

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Cytopathic effects: virus-modulated manifestations of innate immunity?

Cited by 33 publications

References 54 publications

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

Innate Immunity to Adenovirus

Oncolytic polio virotherapy of cancer

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