GENERAL INTRODUCTION: HERPESVIRIDAE

Introduction

Although rhinotracheitis, pustular vulvovaginitis and pustular balanoposthitis are the most common manifestations of disease caused by bovine herpesvirus 1 (BoHV-1), the sites of infection of the virus are not strictly restricted to the respiratory or genital tracts; other syndromes caused by it include those associated with conjunctivitis, abortion or meningoencephalitis.³⁸ It must, however, be borne in mind that BoHV-5 is more frequently associated with fatal meningoencephalitis in cattle than BoHV-1.

In 1913 a vulvovaginitis of cattle called Bläschenausschlag was first described in Europe.¹⁶⁷ It was subsequently shown to be caused by a virus that was isolated from the genital tract of an affected cow.^{71, 161} In parallel, an acute contagious febrile infection of cattle characterized by an intense inflammatory reaction of the upper respiratory tract, which was accompanied by dyspnoea, nasal discharge and depression, was reported and called infectious bovine rhinotracheitis (IBR) to describe its infectious nature and hallmark which is rhinotracheitis.⁸⁴ Although these two distinct syndromes have been referred to in the past as ‘red nose’, ‘dust pneumonia’, infectious necrotic rhinotracheitis, coital exanthema, vesicular venereal disease, or infectious pustular vulvovaginitis (IPV), it has been accepted that they all refer to infection with either bovine herpesvirus 1 (BoHV-1) subtype 1 or 2.^{38, 65, 66, 92, 137}

Aetiology

Bovine herpesvirus 1 is a member of the order Herpesvirales, family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus.¹²² Isolation and characterization of the infectious agent have clearly demonstrated that BoHV-1 can cause the clinical syndromes mentioned above. Although it is common that an animal suffers simultaneously from more than one syndrome, particularly respiratory disease and conjunctivitis, it is rare for an animal to suffer concurrently from both respiratory and genital infections.

Bovine herpesvirus 1  contains a double stranded genome of 135 kilobase pairs (kbp).^{40, 120} The genomic arrangement of BoHV-1 is typical of group D herpesviruses in that the genome is divided into a unique long (UL) segment of approximately 103 kbp and a unique short (US) segment of 32 kbp. While the UL region remains in its prototype orientation, the US region flanked by terminal repeat  (TR) and inverted repeat (IR) regions can exist in two orientations relative to the UL region.⁹³

A total of 73 open reading frames (ORFs) have identified in the BoHV-1 genome,^{131, 160} which encode 11 glycoproteins.^{120, 131} Of the 73 ORFs, only 33 appear to be essential for virus replication.¹²⁰ The requirement of 2 genes (double copy) for virus replication is not clear.¹²⁰ Similar to other alphaherpesviruses, the genome is transcribed in three different stages, viz. immediate early (α), early (β), and late (γ) genes.¹²³ The late gene transcripts occur at the time of viral DNA synthesis. Recent evidence suggests that in addition to BICP0, BCIP4 and BCIP22, BoHV-1 encodes UL21, UL33 and UL34, which are expressed as immediate early genes.¹¹⁴ Interestingly, BoHV-1 also encodes four unique ORFs, UL0.5, UL3.5, Circ and US1.5.¹³¹ Proteomic analysis identified 33 proteins in purified BoHV-1 virions (including 9 envelope proteins, 5 capsid proteins and 19 tegument proteins) and 15 host proteins.⁹

In addition, the BoHV-1 genome encodes 10 microRNAs (miRNA), which are processed into 12 mature miRNAs, and may play a role in BHV-1 latency and post-transcriptional regulation of BoHV-1 transcripts.^{41, 69}

There are three subtypes of BoHV-1: BoHV-1.1, BoHV1.2a, and BoHV1.2b^{101, 120} which have been differentiated by genomic DNA restriction endonuclease fragment polymorphisms.^{96, 97} Subtype 1.1 is more associated with respiratory infections; subtype 1.2a mostly causes respiratory and genital signs; and subtype 1.2b is predominantly associated with genital infections in Wentink et al., 1993.¹⁵⁶ Although all the neurological strains were initially also grouped with BoHV-1, the one most frequently associated with fatal meningoencephalitis in cattle has been reclassified as BoHV-5 based on its unique genomic characteristics.^{124, 137} All isolates of BoHV-1 appear to be antigenically related and even after extensive in vitro or in vivo passage, the isolates retain their antigenicity.³⁹ Studies have clearly indicated the genetic stability of the virus which has significant implications for vaccine development and diagnosis. However, there is some variation in restriction endonuclease DNA fragment patterns that may be useful for...