A novel porcine parvovirus DNA-launched infectious clone carrying stable double labels as an effective genetic platform

Chen, Songbiao; Miao, Bichen; Chen, Nannan; Zhang, Xuezhi; Zhang, Xiujuan; Du, Qian; Huang, Yong; Tong, Dewen

doi:10.1016/j.vetmic.2019.108502

Cited by 4 publications

(7 citation statements)

References 23 publications

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“…Wild-type PCV2 strain (genotype PCV2b; GenBank accession number MH492006.1), PPV (Genbank: MK993540), PRV (Genbank: MH582511.1) and the p32 binding site mutant PCV2 strain (PCV2RmA) are isolated or constructed in our previous study [ 36 , 62 ].…”

Section: Methodsmentioning

confidence: 99%

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

Wang

Chen

et al. 2021

PLoS Pathog

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Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-β induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of cGAS at S278 via activation of PI3K/Akt signaling, which directly silences the catalytic activity of cGAS. Subsequently, phosphorylation of cGAS at S278 can facilitate the K48-linked poly-ubiquitination of cGAS at K389, which can been served as a signal for recognizing by the ubiquitin-binding domain of histone deacetylase 6 (HDAC6), to promote the translocation of K48-ubiquitinated-cGAS from cytosol to autolysosome depending on the deacetylase activity of HDAC6, thereby eventually resulting in a markedly increased cGAS degradation in PCV2 infection-induced autophagic cells relative to Earle’s Balanced Salt Solution (EBSS)-induced autophagic cells (a typical starving autophagy). Importantly, we found that PCV2 Cap and its binding protein gC1qR act as predominant regulators to promote porcine cGAS phosphorylation and HDAC6 activation through mediating PI3K/AKT signaling and PKCδ signaling activation. Based on this finding, gC1qR-binding activity deficient PCV2 mutant (PCV2RmA) indeed show a weakened inhibitory effect on IFN-β induction and a weaker boost effect for other DNA viruses infection compared to wild-type PCV2. Collectively, our findings illuminate a systematic regulation mechanism by which porcine circovirus counteracts the cGAS-STING signaling pathway to inhibit the type I interferon induction and promote DNA virus infection, and identify gC1qR as an important regulator for the immunosuppression induced by PCV2.

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Section: Methodsmentioning

confidence: 99%

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

Wang

Chen

et al. 2021

PLoS Pathog

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“…The dendritic cells (DCs) facilitate the transport of the internalized virus to the lymph nodes for further proliferation [119] and the presentation of specialized cytokines such as granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin-1β (IL-1b), interferon-α (IFN-α), and IL-8, and IFN-γ [54,56,73,80,120]. In addition to innate immune cell recruitment, B-cell, CD4 + , and CD8 + T-cell mediated immune responses are the most common adaptive immunity associated with infected host cells [121]. However, the activated T-cell immunity could not destroy this antigens because the virus releases several virulence factors that prevent possible neutralization of the virion particles, as shown in Figure 2 [122].…”

Section: Overview Of Current Knowledge In Immune Responses Elicited By Orfv Infectionsmentioning

confidence: 99%

“…Inactivated vaccines are prepared by killing or inactivating the viral antigens by heat or chemicals such as formaldehyde and/or formal saline [25]. Thus, inactivated vaccine is relatively safe, cannot reverse virulence, and most importantly, it can be used to vaccinate even immunocompromised animals [121,[162][163][164][165]. It is well-documented that inactivation facilitates the induction of Th1and other T-cell mediated immune responses.…”

Section: Inactivated (Killed) Vaccinesmentioning

confidence: 99%

“…As such, there is a need for adjuvants in the vaccine formulations to improve immunogenicity [84,166]. In addition, inactivated vaccines are relatively expensive to produce due to the additional cost involvement of an adjuvant, purifications, chemicals for inactivation, and most importantly cost implications of multiple uses of booster dosage [121,167]. The inactivated or killed vaccines are further classified into several types including; (1) Inactivated complete (whole) viral pathogens by heat or chemicals e.g., scab-based inactivated vaccine against Orf virus and rabies vaccine; (2) purified protein-based vaccine obtained from killed viral particles or purified antigens produced [120,168].…”

Section: Inactivated (Killed) Vaccinesmentioning

confidence: 99%

“…The replication of parapoxvirus DNA vaccines in the host cytoplasm have shown to induce long-lived immune response at single time point injection [120,150,171]. Thus, the advantages of this type of vaccine over the killed vaccines include prompt antigen presentation [25] and activation of the immune cells, relatively lower cost of production, and highly efficacious in small ruminants [86,121,122]. DNA vaccines are emerging as novel and essential strategies for animal vaccine development [4,12,52,64,170].…”

Section: Dna Vaccinesmentioning

confidence: 99%

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Immunomodulatory Strategies for Parapoxvirus: Current Status and Future Approaches for the Development of Vaccines against Orf Virus Infection

et al. 2021

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Orf virus (ORFV), the prototype species of the parapoxvirus genus, is the causative agent of contagious ecthyma, an extremely devastating skin disease of sheep, goats, and humans that causes enormous economic losses in livestock production. ORFV is known for its ability to repeatedly infect both previously infected and vaccinated sheep due to several immunomodulatory genes encoded by the virus that temporarily suppress host immunity. Therefore, the development of novel, safe and effective vaccines against ORFV infection is an important priority. Although, the commercially licensed live-attenuated vaccines have provided partial protection against ORFV infections, the attenuated viruses have been associated with major safety concerns. In addition to safety issues, the persistent reinfection of vaccinated animals warrants the need to investigate several factors that may affect vaccine efficacy. Perhaps, the reason for the failure of the vaccine is due to the long-term adaptation of the virus in tissue culture. In recent years, the development of vaccines against ORFV infection has achieved great success due to technological advances in recombinant DNA technologies, which have opened a pathway for the development of vaccine candidates that elicit robust immunity. In this review, we present current knowledge on immune responses elicited by ORFV, with particular attention to the effects of the viral immunomodulators on the host immune system. We also discuss the implications of strain variation for the development of rational vaccines. Finally, the review will also aim to demonstrate future strategies for the development of safe and efficient vaccines against ORFV infections.

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Coatomer protein COPƐ, a novel NS1-interacting protein, promotes the replication of Porcine Parvovirus via attenuation of the production of type I interferon

Chen

Miao

et al. 2021

Veterinary Microbiology

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A novel porcine parvovirus DNA-launched infectious clone carrying stable double labels as an effective genetic platform

Cited by 4 publications

References 23 publications

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

Immunomodulatory Strategies for Parapoxvirus: Current Status and Future Approaches for the Development of Vaccines against Orf Virus Infection

Coatomer protein COPƐ, a novel NS1-interacting protein, promotes the replication of Porcine Parvovirus via attenuation of the production of type I interferon

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