Influence of N-glycosylation on Expression and Function of Pseudorabies Virus Glycoprotein gB

Vallbracht, Melina; Klupp, Barbara G.; Mettenleiter, Thomas C.

doi:10.3390/pathogens10010061

Cited by 9 publications

(7 citation statements)

References 65 publications

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“…None of those studies addressed the effects of the N-glycosylation of those viruses' gB on evasion from antibodies and pathogenesis in vivo. In agreement with our observation in this study that the N141Q mutation in HSV-1 gB did not affect viral replication in Vero and SK-N-SH cells, the ectopic expression of the PRV gB-N154Q mutant rescued the entry deficiency of a gBdeficient PRV so that its entry would be at a level similar to that of PRVs with wild-type gB (27). In contrast, the ectopic expression of the HSV-2 gB-N133Q mutant barely rescued the entry deficiency of a gB-deficient HSV-2 (26).…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have characterized N-glycosylation at Asn-133 of the HSV-2 gB and at Asn-154 of the pseudorabies virus (PRV) gB, which correspond to the N-glycosylation at Asn-141 of HSV-1 gB (26, 27). None of those studies addressed the effects of the N-glycosylation of those viruses’ gB on evasion from antibodies and pathogenesis in vivo.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dual Impacts of a Glycan Shield on the Envelope Glycoprotein B of HSV-1: Evasion from Human Antibodies In Vivo and Neurovirulence

Fukui

Maruzuru

Ohno

et al. 2022

Preprint

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Identification of the mechanisms of viral evasion from human antibodies is crucial both for understanding viral pathogenesis and for designing effective vaccines. However, the in vivo efficacy of the mechanisms of viral evasion from human antibodies has not been well documented. Here we show in cell cultures that an N-glycan shield on the HSV-1 envelope glycoprotein B (gB) mediated evasion from neutralization and antibody-dependent cellular cytotoxicity due to pooled γ-globulins derived from human blood. We also demonstrated that the presence of human γ-globulins in mice and HSV-1 immunity induced by viral infection in mice significantly reduced the replication of a mutant virus lacking the glycosylation site in a peripheral organ but had little effect on the replication of its repaired virus. These results suggest that the glycan shield on the HSV-1 envelope gB mediated evasion from human antibodies in vivo and from HSV-1 immunity induced by viral infection in vivo. Notably, we also found that the glycan shield on HSV-1 gB was significant for HSV-1 neurovirulence and replication in the central nervous system (CNS) of naïve mice. Thus, we have identified a critical glycan shield on HSV-1 gB that has dual impacts, namely evasion from human antibodies in vivo and viral neurovirulence.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Dual Impacts of a Glycan Shield on the Envelope Glycoprotein B of HSV-1: Evasion from Human Antibodies In Vivo and Neurovirulence

Fukui

Maruzuru

Ohno

et al. 2022

Preprint

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“…Sequence analysis of viral gB in this study suggests that FcaGHV1 in southwestern Ontario is genetically highly similar to FcaGHV1 found throughout the world. The high conservation of gB is not surprising, given the critical role of gB in mediating herpesvirus-cell fusion [ 49 ]. Identification of FcaGHV1 variants will likely require examination of a less conserved genomic region.…”

Section: Discussionmentioning

confidence: 99%

Detection of Felis catus Gammaherpesvirus 1 in Domestic Cat Saliva: Prevalence, Risk Factors, and Attempted Virus Isolation

Hill,

Satchell,

Troyer

2024

Pathogens

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Felis catus gammaherpesvirus 1 (FcaGHV1) infects domestic cats worldwide, yet it has not been successfully propagated in cell culture, and little is known about how it is shed and transmitted. To investigate the salivary shedding of FcaGHV1, we quantified FcaGHV1 DNA in feline saliva by qPCR. For FcaGHV1-positive saliva, we sequenced a portion of the viral glycoprotein B (gB) gene and attempted to isolate the infectious virus by passage in several felid and non-felid cell lines. We detected FcaGHV1 DNA in 45/227 (19.8%) saliva samples with variable viral DNA loads from less than 100 to greater than 3 million copies/mL (median 4884 copies/mL). Multiple saliva samples collected from an infected cat over a two-month period were consistently positive, indicating that chronic shedding can occur for at least two months. Cat age, sex, and health status were not associated with shedding prevalence or viral DNA load in saliva. Feral status was also not associated with shedding prevalence. However, feral cats had significantly higher FcaGHV1 DNA load than non-feral cats. Sequencing of FcaGHV1 gB showed low sequence diversity and >99.5% nucleotide identity to the worldwide consensus FcaGHV1 gB sequence. We did not detect virus replication during the passage of FcaGHV1-positive saliva in cell culture, as indicated by consistently negative qPCR on cell lysate and supernatant. To our knowledge, these data show for the first time that cats in Canada are infected with FcaGHV1. The data further suggest that shedding of FcaGHV1 in saliva is common, can occur chronically over an extended period of time, and may occur at higher levels in feral compared to non-feral cats.

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“…Previous studies have characterized N-glycosylation at Asn-133 of HSV-2 gB and at Asn-154 of the pseudorabies virus (PRV) gB, which correspond to the N-glycosylation at Asn-141 of HSV-1 gB ( 54 , 55 ). None of those studies addressed the effects of the N-glycosylation of those viruses’ gB on in vivo evasion from antibodies and pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Dual impacts of a glycan shield on the envelope glycoprotein B of HSV-1: evasion from human antibodies in vivo and neurovirulence

Fukui

Maruzuru

Ohno

et al. 2023

mBio

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Identification of the mechanisms of viral evasion from human antibodies is crucial both for understanding viral pathogenesis and for designing effective vaccines. Here we show in cell cultures that an N-glycan shield on the herpes simplex virus 1 (HSV-1) envelope glycoprotein B (gB) mediated evasion from neutralization and antibody-dependent cellular cytotoxicity due to pooled γ-globulins derived from human blood. We also demonstrated that the presence of human γ-globulins in mice and immunity to HSV-1 induced by viral infection in mice significantly reduced replication in their eyes of a mutant virus lacking the glycosylation site but had little effect on the replication of its repaired virus. These results suggest that an N-glycan shield on a specific site of HSV-1 envelope gB mediated evasion from human antibodies in vivo and from HSV-1 immunity induced by viral infection in vivo . Notably, we also found that an N-glycan shield on a specific site of HSV-1 gB was significant for HSV-1 neurovirulence and replication in the central nervous system of naïve mice. Thus, we have identified a critical N-glycan shield on HSV-1 gB that has dual impacts, namely evasion from human antibodies in vivo and viral neurovirulence. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latent and recurrent infections in humans. To produce recurrent infections that contribute to transmission of the virus to new human host(s), the virus must be able to evade the antibodies persisting in latently infected individuals. Here, we show that an N-glycan shield on the specific site of the envelope glycoprotein B (gB) of HSV-1 mediates evasion from pooled γ-globulins derived from human blood both in cell cultures and mice. Notably, the N-glycan shield on the specific site of gB was also significant for HSV-1 neurovirulence in naïve mice. Considering the clinical features of HSV-1 infection, these results suggest that the glycan shield not only facilitates recurrent HSV-1 infections in latently infected humans by evading antibodies but is also important for HSV-1 pathogenesis during the initial infection.

show abstract

Influence of N-glycosylation on Expression and Function of Pseudorabies Virus Glycoprotein gB

Cited by 9 publications

References 65 publications

Dual Impacts of a Glycan Shield on the Envelope Glycoprotein B of HSV-1: Evasion from Human Antibodies In Vivo and Neurovirulence

Dual Impacts of a Glycan Shield on the Envelope Glycoprotein B of HSV-1: Evasion from Human Antibodies In Vivo and Neurovirulence

Detection of Felis catus Gammaherpesvirus 1 in Domestic Cat Saliva: Prevalence, Risk Factors, and Attempted Virus Isolation

Dual impacts of a glycan shield on the envelope glycoprotein B of HSV-1: evasion from human antibodies in vivo and neurovirulence

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