Virus-induced Apoptosis Research Articles

Assessing the oncolytic potential of rotavirus on mouse myeloma cell line Sp2/0-Ag14

Introduction: Cancer is the second leading cause of death in the United States, surpassed only by cardiovascular disease. However, cancer has now overtaken cardiovascular disease as the main cause of death in 12 countries in Western Europe. The burden of cancer is posing a major challenge to health care systems worldwide and demanding improvements in methods for cancer prevention, diagnosis, and treatment. Alternative and complementary strategies for orthodox surgery, radiotherapy, and chemotherapy need to be developed.Objective: To determine the oncolytic potential of tumor cell-adapted rotavirus in terms of their ability to infect and lysate murine myeloma Sp2/0-Ag14 cells.Materials and methods: We inoculated rotaviruses Wt1-5, WWM, TRUYO, ECwt-O, and WTEW in Sp2/0-Ag14 cells and we examined their infectious effects by immunocytochemistry, immunofluorescence, flow cytometry, and DNA fragmentation assays. Results: Rotavirus infection involved the participation of some heat shock proteins, of protein disulfide isomerase (PDI), and integrin β3. We detected the accumulation of viral antigens within the virus-inoculated cells and in the culture medium in all the rotavirus isolates examined. The rotavirus-induced cell death mechanism in Sp2/0-Ag14 cells involved changes in cell membrane permeability, chromatin condensation, and DNA fragmentation, which were compatible with cytotoxicity and apoptosis.Conclusions: The ability of the rotavirus isolates Wt1-5, WWM, TRUYO, ECwt-O, and WTEW to infect and cause cell death of Sp2/0-Ag14 cells through mechanisms that are compatible with virus-induced apoptosis makes them potential candidates as oncolytic agents.

Effect of the Viral Hemorrhagic Septicemia Virus Nonvirion Protein on Translation via PERK-eIF2α Pathway.

Viral hemorrhagic septicemia virus (VHSV) is one of the most deadly infectious fish pathogens, posing a serious threat to the aquaculture industry and freshwater ecosystems worldwide. Previous work showed that VHSV sub-genotype IVb suppresses host innate immune responses, but the exact mechanism by which VHSV IVb inhibits antiviral response remains incompletely characterized. As with other novirhabdoviruses, VHSV IVb contains a unique and highly variable nonvirion (NV) gene, which is implicated in viral replication, virus-induced apoptosis and regulating interferon (IFN) production. However, the molecular mechanisms underlying the role of IVb NV gene in regulating viral or cellular processes is poorly understood. Compared to the wild-type recombinant (rWT) VHSV, mutant VHSV lacking a functional IVb NV reduced IFN expression and compromised innate immune response of the host cells by inhibiting translation. VHSV IVb infection increased phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in host translation shutoff. However, VHSV IVb protein synthesis proceeds despite increasing phosphorylation of eIF2α. During VHSV IVb infection, eIF2α phosphorylation was mediated via PKR-like endoplasmic reticulum kinase (PERK) and was required for efficient viral protein synthesis, but shutoff of host translation and IFN signaling was independent of p-eIF2α. Similarly, IVb NV null VHSV infection induced less p-eIF2α, but exhibited decreased viral protein synthesis despite increased levels of viral mRNA. These findings show a role for IVb NV in VHSV pathogenesis by utilizing the PERK-eIF2α pathway for viral-mediated host shutoff and interferon signaling to regulate host cell response.

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

Viral myocarditis (VMC) is a type of inflammation affecting myocardial cells caused by viral infection and has been an important cause of dilated cardiomyopathy (DCM) worldwide. Type B3 coxsackievirus (CVB3), a non-enveloped positive-strand RNA virus of the Enterovirus genus, is one of most common agent of viral myocarditis. Till now, effective treatments for VMC are lacking due to lack of drugs or vaccine. Lithium chloride (LiCl) is applied in the clinical management of manic depressive disorders. Accumulating evidence have demonstrated that LiCl, also as an effective antiviral drug, exhibited antiviral effects for specific viruses. However, there are few reports of evaluating LiCl's antiviral effect in mice model. Here, we investigated the inhibitory influence of LiCl on the CVB3 replication in vitro and in vivo and the development of CVB3-induced VMC. We found that LiCl significantly suppressed CVB3 replication in HeLa via inhibiting virus-induced cell apoptosis. Moreover, LiCl treatment in vivo obviously inhibited virus replication within the myocardium and alleviated CVB3-induced acute myocarditis. Collectively, our data demonstrated that LiCl inhibited CVB3 replication and negatively regulated virus-triggered inflammatory responses. Our finding further expands the antiviral targets of LiCl and provides an alternative agent for viral myocarditis.

Varicella-Zoster Virus infected human neurons are resistant to apoptosis.

Varicella-zoster virus (VZV) is a pathogenic human herpesvirus that causes varicella (chickenpox) as a primary infection following which it becomes latent in ganglionic neurons. Following viral reactivation many years later VZV causes herpes zoster (shingles) as well as a variety of other neurological syndromes. The molecular mechanisms of the conversion of the virus from a lytic to a latent state in ganglia are not well understood. In order to gain insights into the neuron-virus interaction, we studied virus-induced apoptosis in cultures of both highly pure terminally differentiated human neurons and human fetal lung fibroblasts (HFL). It was found that (a) VZV DNA did not accumulate in infected human neurons; (b) VZV transcripts were present at lower levels at all days studied post-infection in neurons; (c) Western blot analysis showed less VZV IE 63 and very little detectable VZV gE proteins in infected neurons compared with HFL; (d) lower levels of the apoptotic marker cleaved Caspase-3 protein were detected in VZV-infected neurons compared with HFL, and higher levels of the known anti-apoptotic proteins Bcl2, Bcl-XL and also the mitochondrial MT-CO2 protein were found in VZV-infected neurons compared with uninfected cells; and (e) both the MT-CO2 protein and VZV IE 63-encoded protein were detected in infected neurons by dual immunofluorescence. These findings showed that neurons are resistant to VZV-induced apoptosis, which may have relevance to the switching of VZV from a lytic to latent ganglionic neuronal infection.

The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis

Recent reports have shown the critical role of the mitochondrial antiviral signaling (MAVS) protein in virus-induced apoptosis, but the involvement of MAVS in tumorigenesis is still poorly understood. Herein, we report that MAVS is a key regulator of p53 activation and is critical for protecting against tumorigenesis. We find that MAVS promotes p53-dependent cell death in response to DNA damage. MAVS interacts with p53 and mediates p53 mitochondrial recruitment under genotoxic stress. Mechanistically, MAVS inhibits p53 ubiquitination by blocking the formation of the p53-murine double-minute 2 (MDM2) complex, leading to the stabilization of p53. Notably, compared with their wild-type littermates, MAVS knockout mice display decreased resistance to azoxymethane (AOM) or AOM/dextran sulfate sodium salt (DSS)-induced colon cancer. MAVS expression is significantly downregulated in human colon cancer tissues. These results unveil roles for MAVS in DNA damage response and tumor suppression.

Endocrine Involvement in COVID-19: Mechanisms, Clinical Features, and Implications for Care.

Coronavirus 2019 (COVID -19) has rapidly emerged as a global pandemic with multi-system involvement. Involvement of the endocrine system is expected in COVID-19 as the interplay between severe acute respiratory syndrome corona virus-2 (SARS CoV-2) and the endocrine system occurs at multiple levels. The widespread presence of ACE-2 receptors on various tissues suggests scope for direct viral infection. The interactions via the activation of inflammatory mediators and indirect immune-mediated damage are also postulated. Evidence so far suggests that COVID-19 can cause functional hypopituitarism by direct and indirect effects on the hypothalamo-pituitary axis resulting in inappropriate adrenal response to stress. Several reports highlight possible immune-mediated damage to thyroid glands resulting in subacute thyroiditis. COVID-19 is implicated in precipitating hyperglycemia in known diabetics and uncovering insulin resistance in those previously undiagnosed. COVID-19 has also been shown to trigger Type 1 Diabetes with ketosis. Various mechanisms including direct virus-induced beta cell apoptosis and immune-mediated beta-cell damage have been demonstrated. The presence of virus in semen has unclear clinical significance at present. In this mini-review summarize the endocrine manifestations reported so far in COVID-19 disease and explore mechanisms to decipher how SARS CoV-2 may affect various endocrine organs.

Cyprinid Herpesvirus 2 miR-C12 Attenuates Virus-Mediated Apoptosis and Promotes Virus Propagation by Targeting Caspase 8.

DNA viruses, most notably members of the herpesvirus family, generally encode miRNAs to mediate both virus and host genes expression. We previously demonstrated that Cyprinid herpesvirus 2 (CyHV-2) encodes 17 miRNAs that are involved in innate immune signaling pathways. In this study, the function of CyHV-2-encoded miRNA was further investigated in GiCF cells. We found that miR-C4 promoted CyHV-2-induced apoptosis, while miR-C12 decreased CyHV-2-induced apoptosis. miR-C12 targeted to 3′ UTR sequence of caspase 8 and suppressed the expression of caspase 8. Besides, the silencing of caspase 8 by specific siRNA led to the attenuation of CyHV-2-induced apoptosis. Furthermore, caspase 8 was downregulated in cells transfected with miR-C12 during CyHV-2 infection. Overexpression of miR-C12 significantly suppressed CyHV-2-induced apoptosis, while silencing of miR-C12 promoted CyHV-2-induced apoptosis. Finally, inhibition of miR-C12 resulted in suppression of CyHV-2 propagation, overexpression of miR-C12, and CASP8-siRNA-1 facilitated CyHV-2 propagation. Taken together, our results demonstrated that CyHV-2-encoded miR-C12 to suppress virus-induced apoptosis and promoted virus replication by targeting caspase 8.

A natural polymorphism in Zika virus NS2A protein responsible of virulence in mice

Zika virus (ZIKV) infection is currently one of the major concerns in human public health due to its association with neurological disorders. Intensive effort has been implemented for the treatment of ZIKV, however there are not currently approved vaccines or antivirals available to combat ZIKV infection. In this sense, the identification of virulence factors associated with changes in ZIKV virulence could help to develop safe and effective countermeasures to treat ZIKV or to prevent future outbreaks. Here, we have compared the virulence of two related ZIKV strains from the recent outbreak in Brazil (2015), Rio Grande do Norte Natal (RGN) and Paraiba. In spite of both viruses being identified in the same period of time and region, significant differences in virulence and replication were observed using a validated mouse model of ZIKV infection. While ZIKV-RGN has a 50% mouse lethal dose (MLD50) of ~105 focus forming units (FFUs), ZIKV-Paraiba infection resulted in 100% of lethality with less than 10 FFUs. Combining deep-sequencing analysis and our previously described infectious ZIKV-RGN cDNA clone, we identified a natural polymorphism in the non-structural protein 2 A (NS2A) that increase the virulence of ZIKV. Moreover, results demonstrate that the single amino acid alanine to valine substitution at position 117 (A117V) in the NS2A was sufficient to convert the attenuated rZIKV-RGN in a virulent Paraiba-like virus (MLD50 < 10 FFU). The mechanism of action was also evaluated and data indicate that substitution A117V in ZIKV NS2A protein reduces host innate immune responses and viral-induced apoptosis in vitro. Therefore, amino acid substitution A117V in ZIKV NS2A could be used as a genetic risk-assessment marker for future ZIKV outbreaks.

Cell apoptosis regulated by interaction between viral gene alpha 3 and host heterogeneous nuclear ribonucleoprotein K facilitates bovine ephemeral fever virus replication

Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus and causes bovine ephemeral fever of cattle and water buffalo in worldwide. Previous studies have demonstrated that infection with BEFV leads to induction of host cellular apoptosis. However, the role of apoptosis in viral replication and the interaction between viral genes and host genes involved in the process of BEFV-induced apoptosis remains unclear. Herein we investigated the interaction between viral non-structural protein α3 and cellular heterogeneous nuclear ribonucleoprotein K (hnRNP K) in the BEFV-induced apoptosis and its role in virus replication. Overexpression of α3 gene activated caspase 3 and consequently cleaved PARP, ultimately lead to apoptosis. Moreover, virus titer of BHK-21 cells infected with BEFV and then treated respectively by the pan-caspase inhibitor (Z-VAD-FMK) and apoptosis inducer (CCCP) was determined, the results showed that apoptosis promoted viral replication. In addition, knockdown of hnRNP K gene promoted BEFV replication, whereas overexpression of hnRNP K gene had the opposite effects. More importantly, overexpression of hnRNP K inhibited virus-induced apoptosis. Subsequently, it was found that hnRNP K suppressed BEFV replication via degrading viral α3 gene and further inhibited apoptosis induced by α3 gene. Finally, the expression of hnRNP K protein was significantly down-regulated upon BEFV infection, and degradation of hnRNP K protein in BHK-21 cells infected with BEFV was mediated by viral activation of caspase 3. Taken together, these results suggest that apoptosis takes a pivotal role in BEFV replication, and interaction between viral α3 gene and host hnRNP K gene in BEFV-induced apoptosis facilitates BEFV replication.

Influenza A virus-induced apoptosis and virus propagation.

Influenza A viruses (IAVs) are respiratory pathogens that cause severe morbidity and mortality worldwide. They affect cellular processes such as proliferation, protein synthesis, autophagy, and apoptosis. Although apoptosis is considered an innate cellular response to invading infectious pathogens, IAVs have evolved to encode viral proteins that modulate host cellular apoptosis in ways that support efficient viral replication and propagation. An understanding of the modulation of host responses is essential to the development of novel therapeutics for the treatment of IAV infections. In this review, we discuss the IAV lifecycle, biology, and strategies employed by the virus to modulate apoptosis to enhance viral survival and establish an infection.

Ergosterol peroxide suppresses influenza A virus-induced pro-inflammatory response and apoptosis by blocking RIG-I signaling

Ergosterol peroxide has been shown to exhibit anti-tumor, antioxidant and anti-bacterial properties. However, the effects of ergosterol peroxide isolated from the herbal Baphicacanthus cusia root on influenza virus infection remain poorly understood. In the present study, ergosterol peroxide (compound 22) was obtained from the B. cusia root and subjected to investigation regarding its immunoregulatory effect on influenza A virus (IAV)-induced inflammation in A549 human alveolar epithelial cells. The structure of compound 22 isolated from B. cusia root. was elucidated by NMR analyses. Structure determination showed that the chemical structure of compound 22 closely resembles that of ergosterol peroxide. We observed that ergosterol peroxide treatment significantly suppressed IAV-induced upregulation of RIG-I expression. Additionally, ergosterol peroxide inhibited the activation of RIG-I downstream signaling pathways, including p38 MAP kinase and NF-κB, which ultimately resulted in the reduced production of an array of pro-inflammatory mediators and interferons (IFN-β and IFN-λ1). Interestingly, inhibitory effects of ergosterol peroxide on the expression of IFNs did not affect the expression of antiviral effectors or enhance viral replication. On the other hand, ergosterol peroxide effectively abolished the amplified production of pro-inflammatory mediators in cells pretreated with IFN-β (500 ng/ml) prior to IAV infection. Moreover, Annexin V and Hoechst 33258 staining revealed that increased apoptosis of IAV-infected cells was reversed by the presence of ergosterol peroxide. Our findings suggest that ergosterol peroxide from the B. cusia root suppressed IAV-associated inflammation and apoptosis via blocking RIG-I signaling, which may serve as a supplementary approach to the treatment of influenza.

Characterisation of a human antibody that potentially links cytomegalovirus infection with systemic lupus erythematosus

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been linked with the development of systemic lupus erythematosus (SLE). Thus far, molecular mimicry has been implicated as the principal mechanism that explains this association. In this study, we characterise a potential alternative process whereby HCMV contributes to SLE. In a cohort of SLE patients, we show a significant association between HCMV infection and SLE through a human antibody response that targets UL44. UL44 is an obligate nuclear-resident, non-structural viral protein vital for HCMV DNA replication. The intracellular nature of this viral protein complicates its targeting by the humoral response – the mechanism remains unresolved. To characterise this response, we present a thorough molecular analysis of the first human monoclonal antibody specific for UL44 derived from a HCMV seropositive donor. This human antibody immunoprecipitates UL44 from HCMV-infected cells together with known nuclear-resident SLE autoantigens – namely, nucleolin, dsDNA and ku70. We also show that UL44 is redistributed to the cell surface during virus-induced apoptosis as part of a complex with these autoantigens. This phenomenon represents a potential mechanism for the bystander presentation of SLE autoantigens to the humoral arm of our immune system under circumstances that favour a break in peripheral tolerance.

Apoptosis as a primary defense mechanism in response to viral infection in invasive fire ant Solenopsis invicta

Apoptosis is considered an innate defense mechanism of insect hosts at the early stage of pathogen infection. The present study attempts to determine whether apoptosis is involved in defending the fire ant, Solenopsis invicta from a natural viral pathogen Solenopsis invicta virus 1 (SINV-1). Results of TEM examination and TUNEL assay both revealed the signature of apoptosis in the midgut epithelium of SINV-1-infected fire ant larvae. A time-course study was conducted to monitor changes in the dynamics of SINV-1 viral titers and apoptosis levels in the midgut epithelium of SINV-1-infected larvae. We found that the viral titer significantly decreases as apoptosis level increases, suggesting that the apoptotic epithelium constitutes a barrier against dissemination of SINV-1. These findings serve as the very first empirical evidence for the virus-induced apoptosis in ants and also help explain some previously observed mortality patterns and behavioral alterations associated with SINV-1 in fire ants.

Characteristics of enterovirus 71-induced cell death and genome scanning to identify viral genes involved in virus-induced cell apoptosis

Enterovirus 71 (EV71) causes hand-foot-and-mouth disease and severe neural complications in infants and young children. Viral pathogenesis is associated with virus-induced cell death and inflammatory cytokine production, which is usually correlated with the type of programmed cell death. EV71-infected cells were analyzed through microscopy, cell staining, and immunoblotting to determine the characteristics of EV71-induced cell death. Results demonstrated that EV71 infection induced cell shrinkage, nuclear condensation, decreased mitochondrial potential, and membrane phosphatidylserine translocation. Caspase-9 activation, poly (ADP-ribose) polymerase cleavage, and lactate dehydrogenase release were also observed during virus-induced cell death. The activated gasdermin D (GSDMD) and the phosphorylated mixed lineage kinase domain-like protein (p-MLKL) were not detected. These observations indicated that EV71-induced cell death was mainly executed by apoptosis through the intrinsic pathway rather than by GSDMD-mediated pyroptosis and p-MLKL-mediated necroptosis. Genome scanning analysis identified that EV71 2A, 2B, and 3C might be the determinant genes of virus-induced cell death. Further experiments showed that EV71 2A- and 3C-induced cell death exhibited dependence on their protease activities but involved different mechanisms. EV71 2A-induced cell death was correlated with the shut-off of host cap-dependent translation, whereas EV71 3C-induced cell death might not be ascribed to this mechanism. These findings would enhance our understanding of EV71 infection and viral pathogenesis, and help identify antiviral targets.

Senecavirus A 3C Protease Mediates Host Cell Apoptosis Late in Infection.

Senecavirus A (SVA), an oncolytic picornavirus used for cancer treatment in humans, has recently emerged as a vesicular disease (VD)-causing agent in swine worldwide. Notably, SVA-induced VD is indistinguishable from foot-and-mouth disease (FMD) and other high-consequence VDs of pigs. Here we investigated the role of apoptosis on infection and replication of SVA. Given the critical role of the nuclear factor-kappa B (NF-κB) signaling pathway on modulation of cell death, we first assessed activation of NF-κB during SVA infection. Results here show that while early during infection SVA induces activation of NF-κB, as evidenced by nuclear translocation of NF-κB-p65 and NF-κB-mediated transcription, late in infection a cleaved product corresponding to the C-terminus of NF-κB-p65 is detected in infected cells, resulting in lower NF-κB transcriptional activity. Additionally, we assessed the potential role of SVA 3C protease (3Cpro) in SVA-induced host-cell apoptosis and cleavage of NF-κB-p65. Transient expression of SVA 3Cpro was associated with cleavage of NF-κB-p65 and Poly (ADP-ribose) polymerase (PARP), suggesting its involvement in virus-induced apoptosis. Most importantly, we showed that while cleavage of NF-κB-p65 is secondary to caspase activation, the proteolytic activity of SVA 3Cpro is essential for induction of apoptosis. Experiments using the pan-caspase inhibitor Z-VAD-FMK confirmed the relevance of late apoptosis for SVA infection, indicating that SVA induces apoptosis, presumably, as a mechanism to facilitate virus release and/or spread from infected cells. Together, these results suggest an important role of apoptosis for SVA infection biology.

N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis

Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly. Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated. In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV). Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells. However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines. Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.

PMA-triggered PKCε activity enhances Nrf2-mediated antiviral response on fish rhabdovirus infection

Viral infection is often accompanied with alteration of intracellular redox state, especially an imbalance between reactive oxygen species (ROS) production and antioxidant cellular defenses. The previous studies showed that an antioxidant cellular defense system, the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), played an important role against spring viraemia of carp virus (SVCV) infection in fish. To further reveal the mediated mechanism that Nrf2 active state was affected by protein kinase C (PKC), here we evaluated SVCV replication in host cells by treated with a strong activator of PKC phorbol-12-myristate-13-acetate (PMA) and an inhibitor staurosporine. Our results showed that PMA significantly repressed SVCV replication and viral-induced apoptosis in Epithelioma papulosum cyprini (EPC) cell, suggesting that PKC may exhibit an anti-SVCV effect. Likewise, PMA resulted in a higher phosphorylation levels of PKCε rather than PKCα/β to participate in the activation of Nrf2, mainly involved in the activation of Nrf2 phosphorylation of Ser40 to favor Nrf2 translocation to nucleus. Furthermore, the data revealed that PMA up-regulated an antiviral response heme oxygenase-1 (HO1) gene expression that was confirmed as the key player against SVCV infection by HO1 specific siRNA. Overall, this study provided a new therapeutic target for the treatment of SVCV infection, and modulating PKC activity could be used for the prevention and treatment of SVCV.

Tissue Tropism of Chicken Anaemia Virus in Naturally Infected Broiler Chickens

Chicken anaemia virus (CAV) causes chicken infectious anaemia, a severe disease characterized by anaemia and immunosuppression and leading to serious economic losses in the poultry industry worldwide. Although CAV infection has been investigated under experimental conditions, information regarding natural infection is scarce. This report describes an outbreak of CAV infection in 18-day-old broiler chickens and investigates virus tropism in affected birds. Thymic atrophy, pale bone marrow, swelling of the legs and foot ulcers (gangrenous dermatitis) were the most common gross lesions. Severe lymphoid cell depletion in the thymic cortex and presence of intranuclear acidophilic inclusion bodies, depletion of haemopoietic cells in bone marrow and presence of lymphoid infiltrates in several organs were also observed. Immunohistochemical labelling demonstrated the CAV antigens VP1 and VP3 in several organs. The expression of both proteins was similar in the thymic cortex and in the bone marrow, the main target organs of CAV; however, VP3 expression was more abundant in the other organs. Labelling of serial sections showed that CD3+ T lymphocytes might be responsible for the dissemination of the virus from the thymus and bone marrow to other organsand that virus-induced apoptosis, mediated through caspase-3, occurred mainly in the thymus and bone marrow.

Inhibition of H1N1 influenza virus-induced apoptosis by selenium nanoparticles functionalized with arbidol through ROS-mediated signaling pathways

As an effective antiviral agent, the clinical application of arbidol is limited by the appearance of drug-resistant viruses.

Apoptosis induced by Ibaraki virus does not affect virus replication and cell death in hamster lung HmLu-1 cells.

Ibaraki virus (IBAV) is an arbovirus that is transmitted by biting midges and causes Ibaraki disease in cattle. IBAV induces apoptosis in several mammalian cell lines, and apoptosis in turn facilitates IBAV replication. In addition, virus-induced apoptosis may contribute to mammalian-specific pathogenicity considering that some arboviruses induce apoptosis in mammalian cells but not in insect cells. In this study, we found that when hamster lung cells (HmLu-1) are used as a virus host, IBAV causes severe cytopathic effects with little induction of apoptosis. Furthermore, pharmacological inhibition of apoptosis did not affect IBAV-induced cytotoxicity. These results indicate the existence of an apoptosis-independent pathway in which IBAV replicates and exerts cytotoxicity in mammalian cells.