Bovine Herpesvirus 1 Counteracts Immune Responses and Immune-Surveillance to Enhance Pathogenesis and Virus Transmission.

Clinton Jones

doi:10.3389/fimmu.2019.01008

Abstract

Infection of cattle by bovine herpesvirus 1 (BoHV-1) can culminate in upper respiratory tract disorders, conjunctivitis, or genital disorders. Infection also consistently leads to transient immune-suppression. BoHV-1 is the number one infectious agent in cattle that is associated with abortions in cattle. BoHV-1, as other α-herpesvirinae subfamily members, establishes latency in sensory neurons. Stressful stimuli, mimicked by the synthetic corticosteroid dexamethasone, consistently induce reactivation from latency in latently infected calves and rabbits. Increased corticosteroid levels due to stress have a two-pronged effect on reactivation from latency by: (1) directly stimulating viral gene expression and replication, and (2) impairing antiviral immune responses, thus enhancing virus spread and transmission. BoHV-1 encodes several proteins, bICP0, bICP27, gG, UL49.5, and VP8, which interfere with key antiviral innate immune responses in the absence of other viral genes. Furthermore, the ability of BoHV-1 to infect lymphocytes and induce apoptosis, in particular CD4+ T cells, has negative impacts on immune responses during acute infection. BoHV-1 induced immune-suppression can initiate the poly-microbial disorder known as bovine respiratory disease complex, which costs the US cattle industry more than one billion dollars annually. Furthermore, interfering with antiviral responses may promote viral spread to ovaries and the developing fetus, thus enhancing reproductive issues associated with BoHV-1 infection of cows or pregnant cows. The focus of this review is to describe the known mechanisms, direct and indirect, by which BoHV-1 interferes with antiviral immune responses during the course of infection.

Highlights

Abundant expression of the viral encoded latency related (LR) gene occurs in latently infected neurons, but infectious virus is not readily detected [32, 33, 45,46,47,48]
Promyelocytic leukemia zinc finger (PLZF) and Slug are induced more than 15-fold 3 h after DEX treatment, which can enhance productive infection
The IEtu1 promoter that drives bICP0 and bICP4 expression is stimulated by DEX and contains two consensus GR binding sites that are bound by the activated GR [67, 68]

Summary

Introduction

Abundant expression of the viral encoded latency related (LR) gene occurs in latently infected neurons, but infectious virus is not readily detected (maintenance of latency) [32, 33, 45,46,47,48]. Promyelocytic leukemia zinc finger (PLZF) and Slug are induced more than 15-fold 3 h after DEX treatment, which can enhance productive infection. The BoHV-1 genome is GC rich and many viral promoters contain Sp1 consensus binding sites and other GC rich motifs suggesting specific KLF transcription factors bind to viral sequences and stimulate viral transcription during early stages of reactivation from latency. The IEtu1 promoter that drives bICP0 and bICP4 expression is stimulated by DEX and contains two consensus GR binding sites that are bound by the activated GR [67, 68].

Results

Conclusion