The US3 Protein of Pseudorabies Virus Drives Viral Passage across the Basement Membrane in Porcine Respiratory Mucosa Explants

Lamote, Jochen; Glorieux, Sarah; Nauwynck, Hans; Favoreel, Herman

doi:10.1128/jvi.01577-16

Cited by 20 publications

(13 citation statements)

References 36 publications

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“…Although only low numbers of pDC surveil mucosal epithelia in noninfected hosts, upon infection, many pDC may migrate from the bloodstream toward the infection site (23)(24)(25)(26). There, pDC may get into contact with infected epithelial cells and fibroblasts (27,28) and stimulate other components of the immune system (8). The potential of the attenuated PRV Bartha vaccine strain to induce a strong TI-IFN production by pDC may contribute to the efficacy of this highly successful vaccine.…”

Section: Discussionmentioning

confidence: 99%

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells

Lamote

Kestens

Waesberghe

et al. 2017

J Virol

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Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune response, both in the innate response and in shaping the adaptive response, mainly because of their ability to produce massive amounts of type I interferon (TI-IFN). Here, we report that cells infected with the live attenuated Bartha vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a dramatically increased TI-IFN response by porcine primary pDC compared to cells infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of the relatively few examples of a highly successful alphaherpesvirus vaccine, identification of factors that may contribute to its efficacy may provide insights for the rational design of other alphaherpesvirus vaccines. The Bartha vaccine genome displays several mutations compared to the genome of wild-type PRV strains, including a large deletion in the unique short (US) region, encompassing the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker strains harboring the entire Bartha US deletion or single mutations in the four affected US genes, we demonstrate that the absence of the viral gE/gI complex contributes to the observed increased IFN-␣ response. Furthermore, we show that the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased TI-IFN production by porcine pDC. Our data further indicate that the gE/gI glycoprotein complex suppresses TI-IFN production by pDC, which represents the first alphaherpesvirus factor that suppresses pDC activity.IMPORTANCE Several alphaherpesviruses, including herpes simpex virus, still lack effective vaccines. However, the highly successful Bartha vaccine has contributed substantially to eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several countries. The impact of Bartha on the immune response is still poorly understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells (pDC) may play an important role in vaccine development. Here, we show that Bartha elicits a dramatically increased type I interferon (TI-IFN) response in primary porcine pDC compared to wild-type strains. In addition, we found that the gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This is the first description of an immune cell type that is differentially affected by Bartha versus wild-type PRV and is the first report describing an alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may therefore contribute to the rational design of other alphaherpesvirus vaccines.KEYWORDS Bartha, ERK1/2, gE, herpes, immune evasion, interferon, pDC, plasmacytoid dendritic cell, pseudorabies

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Section: Discussionmentioning

confidence: 99%

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells

Lamote

Kestens

Waesberghe

et al. 2017

J Virol

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“…Following replication in the swine respiratory epithelium, PRV may cross the basement membrane (BM) in foci to penetrate the connective tissues and reach the draining lymph nodes and bloodstream [56,72] (Figure 1(1c,d)). The invasion of PRV through the BM towards the lamina propria is mediated by trypsin-like serine protease activity [73].…”

Section: Prv Replication In the Draining Lymph Nodes And Viremiamentioning

confidence: 99%

The Neuropathic Itch Caused by Pseudorabies Virus

Laval

Enquist

2020

Pathogens

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Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it can establish a quiescent, latent infection. While the natural host of PRV is the swine, a broad spectrum of mammals, including rodents, cats, dogs, and cattle can be infected. Since the nineteenth century, PRV infection is known to cause a severe acute neuropathy, the so called “mad itch” in non-natural hosts, but surprisingly not in swine. In the past, most scientific efforts have been directed to eradicating PRV from pig farms by the use of effective marker vaccines, but little attention has been given to the processes leading to the mad itch. The main objective of this review is to provide state-of-the-art information on the mechanisms governing PRV-induced neuropathic itch in non-natural hosts. We highlight similarities and key differences in the pathogenesis of PRV infections between non-natural hosts and pigs that might explain their distinctive clinical outcomes. Current knowledge on the neurobiology and possible explanations for the unstoppable itch experienced by PRV-infected animals is also reviewed. We summarize recent findings concerning PRV-induced neuroinflammatory responses in mice and address the relevance of this animal model to study other alphaherpesvirus-induced neuropathies, such as those observed for VZV infection.

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“…For example, porcine alpha-herpes virus pseudorabies virus can replicate in epithelial cells of the surface mucosa and spread to the whole body via the circulatory system. Epstein–Barr virus can replicate in nasopharyngeal epithelial cells and spread to the whole body via virus-carrying B cells [ 32 – 35 ]. Although the replication of these viruses in mucosal epithelial cells does not produce cytopathic effects, they can serve as a source of infection with the potential to spread at any time [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

PEDV infection in neonatal piglets through the nasal cavity is mediated by subepithelial CD3+ T cells

Yuan

Jin

et al. 2021

Vet Res

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Porcine epidemic diarrhea virus (PEDV) primarily infects neonatal piglets causing catastrophic effects on the global pig farming industry. PEDV infects piglets through the nasal cavity, a process in which dendritic cells (DCs) play an important role. However, neonatal piglets have fewer nasal DCs. This study found that subepithelial CD3+ T cells mediated PEDV invasion through the nasal cavity in neonatal piglets. PEDV could replicate in the nasal epithelial cells (NECs) isolated from the nasal cavity of neonatal piglets. Infection of NECs with PEDV could induce antiviral and inflammatory cytokines at the late stage. The infected NECs mediated transfer of virus to CD3+ T cells distributed in the subepithelial of the nasal cavity via cell-to-cell contact. The infected CD3+ T cells could migrate to the intestine via blood circulation, causing intestinal infection in neonatal piglets. Thus, the findings of this study indicate the importance of CD3+T cells in the dissemination of PEDV from the nasal cavity to the intestinal mucosa in neonatal piglets.

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The US3 Protein of Pseudorabies Virus Drives Viral Passage across the Basement Membrane in Porcine Respiratory Mucosa Explants

Cited by 20 publications

References 36 publications

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells

The Neuropathic Itch Caused by Pseudorabies Virus

PEDV infection in neonatal piglets through the nasal cavity is mediated by subepithelial CD3+ T cells

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