Entry of equid herpesvirus 1 into CD172a+ monocytic cells

Laval, Kathlyn; Favoreel, Herman; Cleemput, Jolien Van; Poelaert, Katrien C. K.; Brown, Ivy K.; Verhasselt, Bruno; Nauwynck, Hans

doi:10.1099/jgv.0.000375

Cited by 4 publications

(8 citation statements)

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“…The 03P37 strain was purified and Dio-labelled as previously described 33 . In PBS treated tracheal ME and nasal ME, a respective total number of 320 ± 28 and 179 ± 61 virus particles was counted on the plasma membrane.…”

Section: Resultsmentioning

confidence: 99%

“…Cellular glycosaminoglycans and sialic acids are known to play a role in the attachment of several herpesviruses, including HSV1, PRV, BoHV1 and EHV1 33 , 37 – 39 . The presence of these cellular glycosaminoglycans and sialic acids was first verified by immunofluorescent staining of respiratory mucosal explant cryosections.…”

Section: Resultsmentioning

confidence: 99%

“…As assessed by immunofluorescent staining, sialic acids were ubiquitously expressed on EREC. Moreover, sialic acids are shown to play a role in EHV1 entry in monocytic CD172a + cells 33 . Therefore, we specifically removed sialic acids with neuraminidase prior to EHV1 inoculation.…”

Section: Discussionmentioning

confidence: 99%

“…Virus purification and subsequent Dio-labelling were performed as described previously 33 , 34 . Full details are given in the supplementary information (SI).…”

Section: Methodsmentioning

confidence: 99%

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Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions

Cleemput

Poelaert

Laval

et al. 2017

Sci Rep

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The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. EHV1 preferentially bound to and entered EREC at basolateral cell surfaces. Restriction of infection via apical inoculation was overcome by disruption of intercellular junctions. Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host’s innate defence against primary alphaherpesvirus infections. In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Virus purification and subsequent Dio-labelling were performed as described previously 33 , 34 . Full details are given in the supplementary information (SI).…”

Section: Methodsmentioning

confidence: 99%

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Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions

Cleemput

Poelaert

Laval

et al. 2017

Sci Rep

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“…However, we cannot refute the possibility that phagocytosis may be a route for viral entry into the cell. Recently in equine herpesvirus-1 (EHV-1), from the genus Varicellovirus, there was an indication of a phagocytic mechanism for EHV-1 to enter some cells (Laval et al, 2016). Alternatively, or in conjunction, PhV-1 may have appropriated the host exocytosis pathway to egress from the cell, as has been noted in other alphaherpesviruses (Fig.…”

Section: Discussionmentioning

confidence: 99%

Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

Rosales

Thurber

2016

PeerJ

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Diseases of marine mammals can be difficult to diagnose because of their life history and protected status. Stranded marine mammals have been a particularly useful resource to discover and comprehend the diseases that plague these top predators. Additionally, advancements in high-throughput sequencing (HTS) has contributed to the discovery of novel pathogens in marine mammals. In this study, we use a combination of HTS and stranded harbor seals (Phoca vitulina) to better understand a known and unknown brain disease. To do this, we used transcriptomics to evaluate brain tissues from seven neonatal harbor seals that expired from an unknown cause of death (UCD) and compared them to four neonatal harbor seals that had confirmed phocine herpesvirus (PhV-1) infections in the brain. Comparing the two disease states we found that UCD animals showed a significant abundance of fatty acid metabolic transcripts in their brain tissue, thus we speculate that a fatty acid metabolic dysregulation contributed to the death of these animals. Furthermore, we were able to describe the response of four young harbor seals with PhV-1 infections in the brain. PhV-1 infected animals showed a significant ability to mount an innate and adaptive immune response, especially to combat viral infections. Our data also suggests that PhV-1 can hijack host pathways for DNA packaging and exocytosis. This is the first study to use transcriptomics in marine mammals to understand host and viral interactions and assess the death of stranded marine mammals with an unknown disease. Furthermore, we show the value of applying transcriptomics on stranded marine mammals for disease characterization.

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An Alphaherpesvirus Exploits Antimicrobial β-Defensins To Initiate Respiratory Tract Infection

Cleemput

Poelaert

Laval

et al. 2020

J Virol

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β-Defensins protect the respiratory tract against the myriad of microbial pathogens entering the airways with each breath. However, this potentially hostile environment is known to serve as a portal of entry for herpesviruses. The lack of suitable respiratory model systems has precluded understanding of how herpesvirus virions overcome the abundant mucosal β-defensins during host invasion. We demonstrate how a central alphaherpesvirus, equine herpesvirus type 1 (EHV1), actually exploits β-defensins to invade its host and initiate viral spread. The equine β-defensins (eBDs) eBD1, -2, and -3 were produced and secreted along the upper respiratory tract. Despite the marked antimicrobial action of eBD2 and -3 against many bacterial and viral pathogens, EHV1 virions were resistant to eBDs through the action of the viral glycoprotein M envelope protein. Pretreatment of EHV1 virions with eBD2 and -3 increased the subsequent infection of rabbit kidney (RK13) cells, which was dependent on viral N-linked glycans. eBD2 and -3 also caused the aggregation of EHV1 virions on the cell surface of RK13 cells. Pretreatment of primary equine respiratory epithelial cells (EREC) with eBD1, -2, and -3 resulted in increased EHV1 virion binding to and infection of these cells. EHV1-infected EREC, in turn, showed an increased production of eBD2 and -3 compared to that seen in mock- and influenza virus-infected EREC. In addition, these eBDs attracted leukocytes, which are essential for EHV1 dissemination and which serve as latent infection reservoirs. These novel mechanisms provide new insights into herpesvirus respiratory tract infection and pathogenesis. IMPORTANCE How herpesviruses circumvent mucosal defenses to promote infection of new hosts through the respiratory tract remains unknown due to a lack of host-specific model systems. We used the alphaherpesvirus equine herpesvirus type 1 (EHV1) and equine respiratory tissues to decipher this key event in general alphaherpesvirus pathogenesis. In contrast to several respiratory viruses and bacteria, EHV1 resisted potent antimicrobial equine β-defensins (eBDs) eBD2 and eBD3 by the action of glycoprotein M. Instead, eBD2 and -3 facilitated EHV1 particle aggregation and infection of rabbit kidney (RK13) cells. In addition, virion binding to and subsequent infection of respiratory epithelial cells were increased upon preincubation of these cells with eBD1, -2, and -3. Infected cells synthesized eBD2 and -3, promoting further host cell invasion by EHV1. Finally, eBD1, -2, and -3 recruited leukocytes, which are well-known EHV1 dissemination and latency vessels. The exploitation of host innate defenses by herpesviruses during the early phase of host colonization indicates that highly specialized strategies have developed during host-pathogen coevolution.

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Entry of equid herpesvirus 1 into CD172a+ monocytic cells

Cited by 4 publications

References 54 publications

Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions

Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions

Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

An Alphaherpesvirus Exploits Antimicrobial β-Defensins To Initiate Respiratory Tract Infection

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