Bovine Herpes Virus

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Bovine Herpes Virus Etiology

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Family: Herpesviridae
Subfamily: Alphaherpesvirinae
Genus: Varicellovirus
Enveloped, ds DNA, 135Kb

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Virion Composition

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Linear ds DNA
Icosahedral capsid
Tegument
Lipid bilayer envelope
Viral glycoproteins

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Subtypes

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BHV-1.1: Mainly respiratory, abortion
BHV-1.2a: Mainly genital
BHV-1.2b: Mainly genital
Classification based on genetic differences since disease pattern is not absolutely type-specific

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Replication

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1) Low affinity virus attachment: Glycoproteins gB and or gC interact w/ heparan sulfate sugar moieties on the cell surface
2) Stable binding btwn gD and cellular nectin-1
3) Viral penetration following fusion btwn the viral envelope and plasma membrane
4) gB, gD, gH, and gI are all involved in this process
5) centripital cytoplasmic transport towards nuclear pores in fx of release of viral DNA. Potential viral tegument or capsid involvement
6) Tegument proteins released (UL 41 is viral host shutoff protein; VP16 is involved in the transactivation of immediate early genes)
7) Regulated expression of 3 different classes of viral genes
8) IE or alpha genes: Encode proteins involved in regulation of the cell cycle
9) E or beta genes: Encode proteins involved in viral replication
10) L or gamma genes: Encode structural proteins incorporated into virions
11) Acquisition of the viral envelope and virus release from the infected cell: primary envelope from inner nuclear membrane, fusion of primary envelope w/ outer nuclear membrane = de-envelopment and capsid release into cytoplasm, acquisition of tegument and mature envelope by budding into a Golgi compartment

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Pathogenesis

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1) Entry and tropsim:
a) Mucous membranes, upper respiratory and genital tracts, conjunctival mucosa, b) direct nose to nose contact, c) aerosol transmission (3-4 ft), d) direct contact at mating, e) genetic differences in glycoprotein C may be involved in tropism determination
2) Replication at portal of entry: a) lytic replication associated w/ cell ballooning and intranuclear inclusions, b) necrosis and delayed onset apoptosis, c) Viral inhibition of migration of repair epi cells to injured areas
3) Rapid dissemination and spread: a) local, b) extracellular release of viral particles, c) direct cell-to-cell spread facilitated by g proteins, d) systemic by viremia, e) mostly cell-free viremia
4) Neuroinvasion: a) association w/ nerve endings of the olfactory and trigeminal nerves, b) does not go beyond first order neurons w/in the trigeminal ganglia, BHV-5 is more neurovirulent

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Immune Response

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Non-specific immunity: a) cytokine secretion leads to recruitment of macrophages, neutrophils, NK cells. Kill virus-infected cells and initiate regulation of specific responses
2) Specific CMI: a) peaks 7-10 days post-infection, coinciding w/ recovery from clinical signs, b) T-helper lymphocytes mediate the lysis of BHV-1 infected cells by activating macrophages and NK cells via IFN gamma and IL-2 secretion and by recruitment and promotion and prliferation of NK cellS
3) Specific humorl immune response: a) detectable from day 10, b) neutralization of cell-free virus, c) participation in Ab-dependent cytotoxicity, d) passive immunity protects the neonate from systemic infection, e) protection against the consequences of reactivation of latent infection
4) Immune evasion strategies: a) gC interacts w/ C3 component of complement, b) BICPO inhibits transcription of type I IFN, c) gG interacts w/ chemokines, d) UL 41 and UL49.5 act together to down regulat MHC-1-associated antigen presentation

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Role of BHV-1 in the Bovine Respiratory Disease (BRD) Complex

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1) Epi damages: a) decreased mucus secretion, b) decreased ciliary activity
2) Decreased activity of alveolar macrophages and neutrophils

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Latency and Reactivation

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1) Nervous: a) local replication, b) association w/ sensory nerve endings, c) retrograde axonal transport, d) establishment of latency in neurons w/in sensory ganglia
2) Lymphoid: a) evidence for latency and reactivation w/in germinal centers
3) Only limited gemone are transcriptionally active during latency
4) Roles of latency-related transcript: a) inhibition of apoptosis, b) inhibition of entry into S phase, c) Inhibition of BICP0
5) Host immunity plays a rold in latency regulation
6) Reactivation Stimuli: a) natural stresses, b) corticosteroids readily induce reactivation, c) only a small proportion of latently infected neurons undergo reactivation, d)reactivated virus uses the same axonal pathway to get back to the periphery, e) Virus amplification at mucosae may or may not lead to re-excretion

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Clinical manifestations

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1) Infectious bovine rhinotracheitis (IBR): a) > 6mos due to passive immunity levels, b) close contact transmission, c) feedlot animals at risk due to low immunity level, high stresses and other viruses and bac, d) occurs in feedlots usually 2-3 wks post-arrival

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Clinical manifestations 2

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IBR signs
1) fever
2) nasal secretion
3) pink muzzle
4) anorexia
5) sudden drop in milk production
6) reddening of the conjunctivae
7) formation of plaques on mucosae
8) Karatitis
9) conjunctivitis
10) recovery w/in 1-2 wks, unless there are secondary bacterial complications (m. hemolytica)

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Clinical manifestations 3

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Infectious Pustular vulvovaginitis
1) fever
2) small pustules on vulvar and caudal vaginal areas
3) tail wagging and painful urination
4) asymptomatic after 2 wks
5) virus excretion for approximately 2 wks

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Clinical manifestations 4

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Infectious balanoposthitis
1) penis and prepuce affected
2) acquired during natural breeding
3) painful lesions, unwillingness to breed
4) signs last up to 4 weeks
5) virus excretion in semen for 14-22 days
6) Lifelong latent infection w/ potential for reactivation

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Clinical manifestations 5

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Abortions
1) Occur at 4-7 mos of gestation
2) BHV-1.1 and BHV-1.2 strains involved
3) Significant time lapse btwn initial clinical signs and abortion
4) time lapse btwn fetal death and abortion leads to various stages of autolysis and aborted fetus

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Diagnosis

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1) clinical signs
2) FA
3) virus isolation
4) PCR
5) Virus neutralization test

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Prevention

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1) MLV IM: a) potential for abortions, b) limited shedding of vacc virus, c) potential for reversion ot virulence
2) MLV intranasal: a) less common, b) rapid onset of protection, c) induction of mucosal immunity (important), d) shedding of vaccine virus, e) potential reversion, f) vacc virus goes latent, but may induce better protection against field virus latency than IM vaccination
3) Inactivated vaccines IM: a) safe, b) more expensive, c) no vacc virus shedding, d) no vacc virus latency, e) no protection against filed virus latency, f) slower induction of protective immune response (7-10 days after second dose), g) shorter duration of immunity-need to revaccinate more often than w/ MLV
4) Vaccination of feedlot cattle: a) first does at 5-6 mos, second dose upon arrival at feedlot
5) Vaccination in cow/calf or dairy herds: a) first dose at 6 mos, b) second dose at 2-3 wks before breeding, c) revaccination at 1-2 yr intervals, d) no MLV vacc during pregnancy
6) Bulls: do not vaccinate if they are to go to an AI station