Bovine herpesvirus 1 tegument protein UL21 plays critical roles in viral secondary envelopment and cell-to-cell spreading.

Farzana Shahin,Aizhen Guo,Sohail Raza,Kui Yang,Yingyu Chen,Huanchun Chen,Changmin Hu

doi:10.18632/oncotarget.21776

Abstract

Bovine herpesvirus 1 (BoHV-1) UL21 is a tegument protein thought to be indispensable for efficient viral growth but its precise function in BoHV-1 is currently unknown. To determine the function of UL21 in BoHV-1 replication, we constructed a mutant virus bearing a UL21 deletion (vBoHV-1-∆UL21) and its revertant virus, vBoHV-1-∆UL21R, in which the UL21 gene was restored using a bacterial artificial chromosome system. The replication of vBoHV-1-∆UL21 was 1,000-fold lower and its plaque size was 85% smaller than those of the wild-type virus (BoHV-1). An ultrastructural analysis showed that deletion of UL21 led to an un-enveloped capsid accumulation in the cytoplasm, whereas nucleocapsid egress was not impaired, suggesting that UL21 is critical for secondary envelopment in BoHV-1. Co-immunoprecipitation assays revealed that HA-tagged UL21 pulled down UL16, suggesting that these two proteins form a complex, and this was further confirmed by a co-immunofluorescence assay. Taken together, these data provide evidence that UL21 plays critical roles in BoHV-1 secondary envelopment, and UL16 is likely to be involved in these activities.

Highlights

Bovine herpesvirus 1 (BoHV-1), an enveloped double-stranded-DNA virus that belongs to the subfamily Alphaherpesvirinae of the Herpesviridae family, causes bovine respiratory disease, vulvovaginitis, abortion, conjunctivitis, balanoposthitis, and severe neonatal disease in cattle [1]
We constructed a UL21 deletion mutant using a BAC system, which revealed the functions of UL21 in BoHV-1 secondary envelopment and cytoplasm exit
Other studies have demonstrated that deleting UL21 in herpes simplex virus (HSV)-1 [12, 23] and pseudorabies virus (PRV) [13, 14] viruses reduced both extracellular and intracellular virus yield and plaque size

Summary

Introduction

Bovine herpesvirus 1 (BoHV-1), an enveloped double-stranded-DNA virus that belongs to the subfamily Alphaherpesvirinae of the Herpesviridae family, causes bovine respiratory disease, vulvovaginitis, abortion, conjunctivitis, balanoposthitis, and severe neonatal disease in cattle [1]. It is divided into three sub-genotypes: BoHV-1.1, BoHV-1.2a, and BoHV-1.2b, which can be differentiated by genomic sequencing and restriction fragment length polymorphisms (RFLPs) [2, 3]. The mature BoHV1 virion consists of a multilayered architecture that is common in all herpesviruses: a capsid enclosing the double-stranded DNA genome, an envelope, and the tegument. All alpha herpesviruses possess more than 15 tegument proteins [5]

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Conclusion