A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex and development of improved vaccines

Abstract

Infection of cattle by bovine herpesvirus type 1 (BHV-1) can lead to upper respiratory tract disorders, conjunctivitis, genital disorders and immune suppression. BHV-1-induced immune suppression initiates bovine respiratory disease complex (BRDC), which costs the US cattle industry approximately 3 billion dollars annually. BHV-1 encodes at least three proteins that can inhibit specific arms of the immune system: (i) bICP0 inhibits interferon-dependent transcription, (ii) the UL41.5 protein inhibits CD8+ T-cell recognition of infected cells by preventing trafficking of viral peptides to the surface of the cells and (iii) glycoprotein G is a chemokine-binding protein that prevents homing of lymphocytes to sights of infection. Following acute infection of calves, BHV-1 can also infect and induce high levels of apoptosis of CD4+ T-cells. Consequently, the ability of BHV-1 to impair the immune response can lead to BRDC. Following acute infection, BHV-1 establishes latency in sensory neurons of trigeminal ganglia (TG) and germinal centers of pharyngeal tonsil. Periodically BHV-1 reactivates from latency, virus is shed, and consequently virus transmission occurs. Two viral genes, the latency related gene and ORF-E are abundantly expressed during latency, suggesting that they regulate the latency-reactivation cycle. The ability of BHV-1 to enter permissive cells, infect sensory neurons and promote virus spread from sensory neurons to mucosal surfaces following reactivation from latency is also regulated by several viral glycoproteins. The focus of this review is to summarize the biology of BHV-1 and how this relates to BRDC.

Assessing the impact of tailored biosecurity advice on farmer behaviour and pathogen presence in beef herds in England and Wales

“…There was also no effect of the 300 intervention on farm-level BHV1 or MAP seropositivity. The lack of any significant pattern of reducing 301 or increasing farm-level BHV1 seropositivity through the course of the study might be explained by 302 the nature of the immunological response to this pathogen, whereby an animal, once infected, can 303 remain seropositive and harbour latent virus indefinitely (Jones and Chowdhury, 2007). The main 304 focus of BHV1 infection control or reduction measures would therefore be to prevent reactivation of 305 carriers, which would subsequently reduce virus circulation and infection of youngstock.…”

Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

“…BHV-1-encoding proteins have a number of immunomodulatory activities, including downregulation of type I interferon responses [15] and expression of class I MHC proteins [16], and interference with chemokine activities [17], which collectively are associated with suppressed cellular immune responses during infection. This immunosuppression is implicated in predisposition to secondary infections with other respiratory pathogens, both viral and bacterial, which cause severe disease and mortality in intensive cattle-rearing units (reviewed in [18]). Vaccination is widely deployed to control disease caused by BHV-1.…”

“…Vaccination is widely deployed to control disease caused by BHV-1. A number of inactivated and live attenuated vaccines are commercially available, but the latter are more commonly used because of the requirement for only one vaccine dose (reviewed in [18,19]). A vaccine using a virus containing a deletion of the gene encoding gE is widely used at present; in addition to being highly attenuated, this virus is incapable of reactivation and its use allows differentiation of infected from vaccinated animals based on detection of serological responses to gE [20].…”

Bovine herpesvirus type 1 as a novel oncolytic virus

“…Acute BHV-1 infection causes lesions on mucosal surfaces, followed by the establishment of life-long latency in neurons. 17 BHV-1 induces bovine respiratory disease, also known as 'shipping fever,' through transient immunosuppression. 17 This phenomenon is mostly associated with reactivation of the virus from latency following a stress response.…”

“…17 BHV-1 induces bovine respiratory disease, also known as 'shipping fever,' through transient immunosuppression. 17 This phenomenon is mostly associated with reactivation of the virus from latency following a stress response. In the absence of bacterial pneumonia seen in shipping fever, BHV-1 symptoms are typically cleared within 2-6 days.…”