The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line

Osada, Naoki; Kohara, Arihiro; Yamaji, Taiki; Hirayama, Noriko; Kasai, Fumie; Sekizuka, Tsuyoshi; Kuroda, Makoto; Hanada, Kentaro

doi:10.1093/dnares/dsu029

Cited by 205 publications

(204 citation statements)

References 45 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…BEAS-2B cells, a bronchial epithelial cell line, were used because the epithelial cells of the lung are the natural site of infection for PIV-3. Vero cells were used as a tool to study the IFNresponse independent of that of IFN-␣/␤ because they are unable to produce type I IFNs (22)(23)(24). Here, we demonstrate that IL-29 message is upregulated during PIV-3 infection in both Vero and BEAS-2B cells.…”

Section: Importancementioning

confidence: 65%

“…We therefore chose to repeat these experiments in a model independent of type I IFN. Vero cells were specifically used because several previous studies have shown that they are not able to produce type I IFNs (22)(23)(24). As in the BEAS-2B cells, Vero cells were infected at an MOI of 2 with TtPIV-1, BPIV-3, or HPIV-3, and expression levels of the type III IFNs (IL-28 and IL-29) were measured by real-time PCR at multiple time points after infection.…”

Section: ϫ⌬⌬Ctmentioning

confidence: 99%

See 1 more Smart Citation

Parainfluenza Virus 3 Blocks Antiviral Mediators Downstream of the Interferon Lambda Receptor by Modulating Stat1 Phosphorylation

Eberle

McGill

Reinhardt

et al. 2016

J Virol

View full text Add to dashboard Cite

Parainfluenza viruses are known to inhibit type I interferon (IFN) production; however, there is a lack of information regarding the type III IFN response during infection. Type III IFNs signal through a unique heterodimeric receptor, IFN-R1/interleukin-10R2 (IL-10R2), which is primarily expressed by epithelial cells. Parainfluenza virus 3 (PIV-3) infection is highly restricted to the airway epithelium. We therefore sought to examine type III IFN signaling pathways during PIV-3 infection of epithelial cells. We used three strains of PIV-3: human PIV-3 (HPIV-3), bovine PIV-3 (BPIV-3), and dolphin PIV-1 (Tursiops truncatus PIV-1, or TtPIV-1). Here, we show that message levels of IL-29 are significantly increased during PIV-3 infection, yet downstream antiviral signaling molecules are not upregulated to levels similar to those of the positive control. IMPORTANCEParainfluenza virus (PIV) in humans is associated with bronchiolitis and pneumonia and can be especially problematic in infants and the elderly. Also seen in cattle, bovine PIV-3 causes respiratory infections in young calves. In addition, PIV-3 is one of a number of pathogens that contribute to the bovine respiratory disease complex (BRDC). As their name suggests, interferons (IFNs) are produced by cells to interfere with viral replication. Paramyxoviruses have previously been shown to block production and downstream signaling of type I IFNs. For the first time, it is shown here that PIV-3 can induce protective type III IFNs in epithelial cells, the primary site of PIV-3 infection. However, we found that PIV-3 modulates signaling pathways downstream of the type III IFN receptor to block production of several specific molecules that aid in a productive antiviral response. Importantly, this work expands our understanding of how PIV-3 effectively evades host innate immunity. P arainfluenza virus 3 (PIV-3) causes a prominent respiratory infection in both cattle and humans. The CDC reports that, in humans, most children have antibodies against human PIV-3 (HPIV-3) by 5 years of age (http://www.cdc.gov/parainfluenza /hcp/clinical.html). There is currently no vaccine available for control of HPIV-3 infection; however, a few studies have examined the use of an attenuated bovine PIV-3 (BPIV-3) to protect against HPIV-3 because of the homology between bovine and human strains (1-3). Given the lack of an efficacious vaccine for HPIV-3, there is a critical need to understand the mechanisms of HPIV-3-induced disease and the molecular pathways associated with viral modulation of the host antiviral defenses.Paramyoxviruses are negative-sense single-stranded RNA viruses which are part of the Paramyxoviridae family and Paramyxovirinae subfamily (4). PIV-3 is found within the genus Respirovirus. PIV-3 is a respiratory virus that primarily infects the epithelial cells of the lung. Symptoms of HPIV-3 infection include bronchiolitis and pneumonia, and HPIV-3 is especially problematic in infants (4). Airway epithelial cells recognize viral infection through pattern recog...

show abstract

Section: Importancementioning

confidence: 65%

Section: ϫ⌬⌬Ctmentioning

confidence: 99%

Parainfluenza Virus 3 Blocks Antiviral Mediators Downstream of the Interferon Lambda Receptor by Modulating Stat1 Phosphorylation

Eberle

McGill

Reinhardt

et al. 2016

J Virol

View full text Add to dashboard Cite

show abstract

“…HFF, human diploid cells have both the intrinsic and the innate immune system functioning. Vero cells are incapable of producing type I interferon as many of the type I interferon genes are missing because of a ∼9 Mb deletion on chromosome 12 (Osada et al, 2014); thus they have a dysfunctional innate immunity. U2OS do not express ATRX and have lower expression of other intrinsic immunity proteins (Lukashchuk and Everett, 2010), thus exhibiting impaired intrinsic immunity and facilitating genomes expression.…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Inhibitors Reduce the Number of Herpes Simplex Virus-1 Genomes Initiating Expression in Individual Cells

et al. 2016

View full text Add to dashboard Cite

Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1) fluorescence expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s). Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA), Suberohydroxamic Acid, Valporic Acid, and Suberoylanilide Hydroxamic Acid. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero, and U2OS), which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (promyelocytic leukemia and ATRX), which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in differences in the number of genomes that initiate expression.

show abstract

“…The Vero cell line, immortalized (non-transformed) Chlorocebus Sabaeus kidney cells, is a staple of viral vaccine manufacture (56). Vero cells cannot mount type 1 IFN responses upon virus infection (57), because they lost the type 1 IFN gene cluster during serial passage in tissue culture (58). Therefore, it cannot be assumed that high-passage clonal cancer cell lines accurately represent the IFN status of their tissue of origin.…”

Section: The Innate Antiviral Responsementioning

confidence: 99%

Recombinant Poliovirus for Cancer Immunotherapy

Gromeier

Nair

2018

Annu. Rev. Med.

View full text Add to dashboard Cite

Mechanisms to elicit antiviral immunity, a natural host response to viral pathogen challenge, are of imminent relevance to cancer immunotherapy. ‘Oncolytic’ viruses, naturally existing or genetically engineered viral agents with cell type-specific propagation in malignant cells, were ostensibly conceived for their tumor cytotoxic properties. Yet, their true therapeutic value may rest in their ability to provoke antiviral signals that engage antitumor immune responses within the immunosuppressive tumor microenvironment. Coopting such ‘oncolytic’ viral agents to instigate antitumor immunity is not an easy feat. During co-evolution with their hosts, viruses acquired sophisticated strategies to block inflammatory signals, intercept innate antiviral interferon responses and prevent antiviral effector responses, e.g. by interfering with antigen presentation and T cell costimulation. The resulting struggle of host innate inflammatory and antiviral responses vs. viral immune evasion and suppression, determines the potential for antitumor immunity to occur. Moreover, paradigms of early host:virus relations established in normal immunocompetent organisms may not hold in the profoundly immunosuppressive tumor microenvironment. In this review, we explain the mechanisms of recombinant non-pathogenic poliovirus, PVSRIPO, which is currently in Phase-1 clinical trials against recurrent glioblastoma. We focus on an unusual host:virus relationship, defined by the simple and cytotoxic replication strategy of poliovirus, which generates inflammatory perturbations conducive to tumor antigen-specific immune priming.

show abstract

The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line

Cited by 205 publications

References 45 publications

Parainfluenza Virus 3 Blocks Antiviral Mediators Downstream of the Interferon Lambda Receptor by Modulating Stat1 Phosphorylation

Parainfluenza Virus 3 Blocks Antiviral Mediators Downstream of the Interferon Lambda Receptor by Modulating Stat1 Phosphorylation

Histone Deacetylase Inhibitors Reduce the Number of Herpes Simplex Virus-1 Genomes Initiating Expression in Individual Cells

Recombinant Poliovirus for Cancer Immunotherapy

Contact Info

Product

Resources

About