Bovine alphaherpesvirus 2 infections

Previous author: E P J GIBBS

Current author:
E P J GIBBS - Retired Emeritus Professor, BVSc, PhD, FRCVS, College of Veterinary Medicine, University of Florida, Veterinary Academic Building V3-157, 2015 SW 16th Avenue, Gainesville, Florida, 32608, USA

GENERAL INTRODUCTION: HERPESVIRIDAE

Introduction

Bovine alphaherpesvirus 2 (BHV-2) causes naturally occurring skin disease in cattle. In temperate areas of the world (e.g. the UK), it is generally characterized by the development of an ulcerative condition of the skin of the teats and udder of dairy cattle [bovine herpes mammillitis (BHM), bovine ulcerative mammillitis, ‘udder gangrene’], whereas in the hotter regions of the world (e.g. most parts of Africa) a generalized skin disease [pseudo-lumpy skin disease (PLSD), Allerton disease] is a more frequent manifestation of infection with the virus. Certain other domestic and laboratory species can be infected experimentally. Surveys in Africa indicate that several wildlife species may become subclinically infected.

The aetiological association of a herpesvirus with PLSD was first reported in South Africa in 1957,¹ the isolate being designated the Allerton strain.  In 1964, the virus was isolated from dairy herds in the British Isles affected with extensive teat infections.⁴⁶ At one time, the virus causing BHM was considered to have been a recent introduction from Africa, but subsequently, in the late 1960s, 1970s and 1980s, it was isolated from cases of PLSD in the USA,⁷²  and from teat infections in dairy cattle in the USA,⁶⁹ Canada,³⁸ Australia,⁶⁷ several European countries,^{9, 21, 47} and Brazil.² An Italian isolate of BHV-2 from an oral lesion in a calf has been extensively studied,⁷ and found to be no different from other European isolates. While there are many countries that have not reported clinical disease in their cattle populations, serological surveys indicate that the virus probably has a worldwide distribution.^{25, 26, 65} It is unlikely that the BHV-2, now present almost worldwide, originated from Africa.

From the perspective of the cattle industry, as a whole, the economic importance of disease caused by BHV-2 is minimal, but, to the individual farmer facing an outbreak of BHM, it may mean the difference between profit and loss for that year. Secondary bacterial mastitis is a common sequel to BHM, often necessitating drying off the cow.  In severe cases of BHM casualty slaughter may be necessary for welfare reasons.³⁰

Despite the fact that infections with BHV-2 have now been recognized for over 60 years, there are aspects related to the pathogenesis and epidemiology which are not fully understood. For example, in temperate regions of the world, outbreaks of BHM predominate while PLSD outbreaks are rare, and BHM occurs only in late summer and early autumn.

Latency has been demonstrated as a sequel to BHV-2 infections in cattle,^{6, 43} but how this relates to the seasonal occurrence of the disease is still unknown. For a historical perspective of the early studies on these diseases, there are several comprehensive reviews available.^{8, 13, 41}

Aetiology

The causal virus of both BHM and PLSD is classified as bovine alphaherpesvirus 2 (BHV-2) within the family Herpesviridae, subfamily Alphaherpesvirinae, genus Simplexvirus, on the basis of the structure of its genome and general biological characteristics.²⁷ https://talk.ictvonline.org/taxonomy/ This genus also includes human alphaherpesviruses 1 and 2 (herpes simplex viruses 1 and 2) and the B virus of macaques (macacine alphaherpesvirus 1). Bovine alphaherpesvirus 2 is included in this genus on the basis of antigenic relationships and similarities in four genes within the 15 kb U-L 23-29 cluster of the DNA genome.^{11, 46, 48, 50, 61, 62, 64, 73} Thus, it has been argued, from this apparently close evolutionary relationship, that the virus may represent a greater hazard to public health than has previously been appreciated^{11, 45} but no clinical disease has, as yet, been recorded in humans exposed to the virus.

The BHV-2 strains isolated in different parts of the world appear to be serologically and genetically similar, irrespective of whether they caused BHM or PLSD.^{20, 37}

Foetal bovine testis and bovine kidney cell monolayers are particularly sensitive for the isolation and growth of BHV-2.¹³ The cytopathic effect (CPE) of BHV-2 in cell culture is characterized by the formation of large syncytia with most of the nuclei containing intranuclear inclusion bodies.⁴² The syncytia often enlarge to contain as many as 1 000 nuclei before they detach from the surface of the culture vessel. Cytopathic effect may be noticed within 24 hours of inoculation. Only rarely is it necessary to culture beyond four days to detect CPE. Other cell types, including cells of human origin, support the growth of the virus.⁴⁵

For a herpesvirus, BHV-2 is moderately resistant to thermal decay once outside the protective environment of the cell. Even after 105 days at ambient room temperature, infective virus could still be recovered from vials (the titre decreased from 8,4 log¹⁴ tissue culture infective doses 50 per cent [TCID₅₀]/ml to 2,5 log¹⁰ TCID₅₀/ml).⁵⁴ The virus is inactivated readily by iodophore disinfectants, less effectively by hypochlorites.³⁹

Epidemiology

The dramatic economical impact of BHM in dairy herds in the 1960s in the UK initially led to the misconception that the...