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Order Herpesvirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The visualization of pseudorabies virus (PrV), a member of the Suid alphaherpesvirus 1 species, causing Aujeszky’s disease in swine, was achieved by numerous approaches. First, Smith et al. (2001) realized the chimeric PrV virions by the N-terminal addition of GFP to the capsid protein VP26. As a result, the authors tracked the individual chimeric PrV capsids as they moved in axons away from infected neuronal cell bodies in culture. Next, Luxton et al. (2005) engineered the dual-fluorescent and FLAG-tagged viruses derived from the infectious PrV clone, where the dual-fluorescent PrV expressed capsids fused to the mRFP1 and a tegument protein fused to the GFP. Moreover, Bohannon et al. (2012) described the fusion of the fluorescent proteins to the three PrV proteins that allowed imaging of capsids in both in vitro and in vivo infection models. The PrV strains expressing the fluorescent pUL25 and pUL36 (VP1/2) preserved wild-type properties better than the traditional fluorescent pUL35 (VP26) isolates in assays of plaque size and virulence in mice.
Interleukin 12: A Potent Vaccine Adjuvant for Promoting Cellular Immunity and Modulating Humoral Immunity
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Therapeutic benefit as a consequence of the activity of IL-12 in modulating and enhancing humoral immunity has been demonstrated in several models. Schijns et al. [32] demonstrated that IL-12 as adjuvant with an inactivated pseudorabies virus (PRV) vaccine enhanced protection from lethal challenge. Resistance correlated with increased serum titers of PRV-specific IgG2a and was dependent on IFN-γ expression. In a second model, Wynn et al. [33] demonstrated that multiple immunizations with irradiated S. mansoni cercariae + IL-12 enhanced expression of antigen-specific IgG2a, IgG2b, and IgG1 isotypes and that the serum from these mice increased protection in naive recipients.
Regulation of Antiviral Immunity by Mitochondrial Dynamics
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Mohsin Khan, Hasan Imam, Saiful Anam Mir
Pseudorabies virus (PRV) is also known to disrupt mitochondrial dynamics and cause calcium imbalance in infected cells. PRV encoded proteins interfere with mitochondrial function via direct translocation to mitochondria (Kramer and Enquist, 2012). These events induced by PRV are required to block apoptotic pathways. Glycoprotein B (gB) of PRV induces mitochondrial fission during PRV infection and results in electrical coupling of neurons, which subsequently increases intracellular calcium (Kramer and Enquist, 2012). Modulation in calcium regulates the mitochondrial motility. Imbalance in calcium regulates the activity of calcium sensitive cellular protein Miro, which then reduces recruitment of kinesin-1 to mitochondria. Kinesin 1 recruitment is required for mitochondrial motility. PRV mediated disruption of mitochondrial dynamics is required for efficient growth and spreading of the virus, which demonstrate that altered mitochondrial transport increases alphaherpesvirus infection and pathogenesis (Kramer and Enquist, 2012).
Molecular engineering tools for the development of vaccines against infectious diseases: current status and future directions
Published in Expert Review of Vaccines, 2023
Wenhui Xue, Tingting Li, Ying Gu, Shaowei Li, Ningshao Xia
Wang et al. rationally developed the first VZV skin and neuro-attenuated live vaccine candidate for varicella, an ORF7-deficient vaccine based on the reverse genetics method using Cre-LoxP-mediated recombination tools, referred to as v7D [34]. v7D exhibits immunogenicity both in vitro and in multiple small animal species, is well-tolerated, and retains the potency to elicit a protective immune response in children [35]. The vaccine has advanced to a Phase I clinical trial in China (ChiCTR1900022284). Utilizing the Cre/Lox tool, Liang and colleagues introduced a novel vaccine development strategy to combat the reemerging pseudorabies virus (PRV). This system enables the precise excision of the marker gene on the viral strain, accelerating PRV vaccine development and ensuring the vaccine’s safety. The effectiveness of the candidate PRV vaccine was confirmed through vaccination and virus challenge experiments [36]. These studies demonstrate the value of Cre/LoxP as a valuable research tool for rapid antiviral vaccine development in the future. Although Cre/LoxP has been widely used in genetic research, it has some limitations that can affect its precision and accuracy (Table 1) [37]. Some pseudo-LoxP sites have been identified, which possess sufficient identity to allow Cre recombinase binding and subsequent recombination at unintended sites [38]. The extent of the problem may vary considerably from study to study but should still be carefully considered.
Bilateral Necrotizing Retinitis following Encephalitis Caused by the Pseudorabies Virus Confirmed by Next-Generation Sequencing
Published in Ocular Immunology and Inflammation, 2021
Feng Hu, Jiawei Wang, Xiao-Yan Peng
The pseudorabies virus (PRV), also called Aujeszky disease virus or Suid herpesvirus1, is a member of the Alphaherpesvirinae subfamily within the family Herpesviridae. PRV primarily infects swine, causing fatal encephalitis in newborn piglets, respiratory disorders in adult pigs and reproductive failure in saws. In addition, PRV may infect certain intermediate hosts, including cats, cattle and dogs. Humans are not intermediate hosts of PRV. However, in recent years, human encephalitis caused by PRV has been reported. The next-generation sequencing (NGS) and polymerase chain reaction (PCR) confirmed the presence of PRV in the cerebrospinal fluid (CSF) and peripheral blood, and immunological tests further validated the presence of PRV in the peripheral blood.1,2 In a case series including four viral encephalitis cases caused by PRV, two cases with ocular involvement were mentioned with limited details. One case was diagnosed with acute bilateral retinitis 11 days after the onset of neurological symptoms. The other case showed bilateral visual acuity of no light perception after the recovery of consciousness and was diagnosed with bilateral retinitis and optic neuritis with right retinal detachment.3 Ocular involvement was reported as the main symptom in a case without PRV central nervous system infection.4 We report a case of bilateral necrotizing retinitis following encephalitis caused by PRV, in whom the etiology was confirmed by NGS for the vitreous specimen.
The potential of currently unavailable herpes virus vaccines
Published in Expert Review of Vaccines, 2018
Július Rajčáni, Ferenc Bánáti, Kálmán Szenthe, Susan Szathmary
Examples of animal herpesvirus vaccines in practical use are the infectious bovine rhinotracheitis live attenuated virus vaccine, the pseudorabies virus live attenuated virus vaccine (with the gE and thymidine kinase genes deleted and the hog cholera virus gE1 gene inserted), the inactivated equine abortion virus (equine herpesvirus 1) combined with the equine rhinopneumonitis virus (equine herpesvirus 4) vaccine in a single product, the feline herpesvirus 1 inactivated and/or attenuated virus vaccines, the avian infectious rhinotracheitis (gallid herpesvirus 1) attenuated virus vaccine, the Marek disease (gallid herpesvirus 2) attenuated live virus vaccine, and the duck enteritis (anatid herpesvirus 1) live attenuated virus vaccine [90]. The nucleotide and amino acid sequences of the Marek’s disease virus (MDV) meq oncoprotein have shown a significant similarity between the strains isolated in Poland and reference strains tested, though some of point mutations were specific just for the Polish strains. The comparison of the meq sequences also revealed a number of single substitutions as well as two poly-amino acid insertions among the strains defined as mild pathogenic and in one attenuated vaccine strain (CVI988-Rispens) points at the close relationship between nucleotide and/or amino acid changes of analyzed MDV strains on one hand and their virulence on other hand [91]. Another disease which should not be neglected is the duck plague caused by the anatid herpesvirus 1, also called duck enteritis virus (DEV). This virus might endanger the mass waterfowl production, namely due to its possible spread from the nature to domestic birds. The epidemiology of DEV in Poland was assessed using a relatively simple real-time loop-mediated isothermal amplification procedure. This technique showed the presence of DEV in 96 out of 132 birds (72.7%), such as wild ducks (Anas platyrhynchos) and mute swans (Cygnus olor) and several other species. The findings in question confirmed the high prevalence of DEV among free-living water birds, a situation not excluding the possible transmission to other birds settling the water environment [92]. These results discussed also indicate the need of vaccination of domestic ducks, geese, and swans as well as of another waterfowl, since their contact with migratory birds and/or possible ingestion of contaminated water by domesticated ducks may not be safely excluded.