Dataset Information

Pseudorabies virus infection inhibits autophagy in permissive cells in vitro.

ABSTRACT: A large number of studies have demonstrated that autophagy is involved in the infection processes of different pathogens. Autophagy is now recognized as an essential component of innate and adaptive immunity. Several herpesviruses have developed various strategies to evade this antiviral mechanism. Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes devastating disease in infected pigs. In this study, we described the interaction between PRV and autophagy for the first time. PRV infection had a dual effect on the cell autophagy response; during the early period of infection, PRV virions induced autophagy without viral replication, and with viral protein expression, PRV reduced the basal level of autophagy in several permissive cells. We observed that inhibit the level of autophagy could increase the titer of infectious PRV. We also found that the conserved alphaherpesvirus US3 tegument protein may reduce the level of autophagy via activation of the AKT/mTOR pathways in PRV infected cells. These findings suggest that autophagy likely contributes to clearance of PRV, and that the virus has evolved strategies to antagonize this pathway.

SUBMITTER: Sun M

PROVIDER: S-EPMC5216355 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pseudorabies virus infection inhibits autophagy in permissive cells in vitro.

Sun Mingxia M Hou Linlin L Tang Yan-Dong YD Liu Yonggang Y Wang Shujie S Wang Jingfei J Shen Nan N An Tongqing T Tian Zhijun Z Cai Xuehui X

Scientific reports 20170106

A large number of studies have demonstrated that autophagy is involved in the infection processes of different pathogens. Autophagy is now recognized as an essential component of innate and adaptive immunity. Several herpesviruses have developed various strategies to evade this antiviral mechanism. Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes devastating disease in infected pigs. In this study, we described the interaction between PRV and autophagy for the ...[more]

PMID: 28059118

Similar Datasets

Project description:Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV-infected animals.

Project description:Pseudorabies virus (PRV), a swine alphaherpesvirus, is a double-stranded DNA virus. It may infect various animals, especially pigs. PRV infection in pigs leads to high mortality rates, and causes huge economic lose for swine industry. Currently, there are few effective antiviral treatments available. Rosmarinic acid (RA), a hydrophilic phenolic compound, shows potential for inhibiting herpes simplex virus. Given that PRV is a member of the Herpesviridae family, this study investigated the antiviral effects of RA against PRV infection through both in vitro and in vivo, as well as the underlying molecular mechanisms. PK-15 cells were used to assess the cytotoxicity of RA in vitro, followed by an investigation of its anti-PRV activity. The study then explored how RA regulates the cGAS-STING signaling pathway, along with inflammatory and apoptotic factors in PRV-infected cells. Molecular docking and dynamics simulations further elucidated the binding interactions between RA and cGAS-STING, providing insight into how RA activates the cGAS-STING pathway against PRV infection. In vivo, the antiviral efficacy of RA was evaluated in a PRV-infected mouse model by assessing tissue viral genome copies, the innate immune cGAS-STING signaling pathway activation, and inflammatory and apoptotic responses. The results showed that RA exhibited a half-maximal cytotoxic concentration (CC50) of 26.23 µg/mL on PK-15 cells and a half-maximal inhibitory concentration (IC50) of 0.84 µg/mL against PRV, resulting in a selectivity index (SI) of 31.22. These findings suggest that RA is a highly effective and low-toxicity compound. RA significantly inhibited PRV adsorption, penetration, and replication within cells. Additionally, while PRV infection suppresses the cGAS-STING signaling pathway, RA treatment activates the innate immune response, enhances downstream antiviral effector IFN-β expression, and reduces inflammation and apoptosis in PRV-infected cells. Molecular docking results showed that the docking scores of cGAS_RA and STING_RA complexes were both less than - 5 kcal/mol, suggesting that RA binds well to cGAS and STING proteins. Molecular dynamics simulations, including RMSD, RMSF, and MM-GBSA analyses, confirmed the high binding stability of cGAS with RA, further validating the potential activity of RA as a cGAS agonist. In vivo studies revealed that RA dramatically lowered viral genome copies in various organs, activated the cGAS-STING signaling pathway, inhibited PRV-induced inflammation and apoptosis, alleviated clinical symptoms, and decreased mortality rate in PRV-infected mice. Overall, RA significantly inhibited PRV proliferation in vitro and in vivo, effectively reduced inflammation and apoptosis, and decreased the mortality rate in infected mice. The study supports the development of RA as an antiviral drug and emphasizes its potential as a candidate for PRV therapy.

Dataset Information

Pseudorabies virus infection inhibits autophagy in permissive cells in vitro.

Publications

Pseudorabies virus infection inhibits autophagy in permissive cells in vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets