Bovine Viral Diarrhea Virus

how is BVDV diagnosed using serology?

*serology* - (up to 90% of cattle may be seropositive for BVD) - serum neutralization or ELISA - single vs. paired titers - seroconversion most useful (PIs may not seroconvert) - affected vs. non-affected group comparisons - type specific serology (type 1 vs. 2) - *pre-colostral titer* (congenitally infected calves, i.e., 10/10 calves make PI presence in herd virtually impossible)

how is BVDV diagnosed using virus isolation?

*virus isolation* - acute (buffy coat) vs. PI (serum) has much higher virus - CP vs. NCP (immunofluorescent or IHC to show viral presence) - virus from clinical samples include buffy coat, serum, nasopharyngeal or ocular swabs, lymphoid or intestinal tissues at necropsy

what are the 2 biotypes of the BVD virus (agent)?

- *NCP* (non-cytopathic): responsible for most dz; major form of virus in cattle & other hosts - *CP* (cytopathic): found only in cattle w/ mucosal dz (poss. some abortions); most vax isolates; most lab ref. isolates; occurs from mutation/ reassort. of NCP virus

what is the pathogenesis of transplacental NCP BVDV infection btwn 125-150 days of gestation?

- *congenital abnormalities* (esp. cerebellar hypoplasia & ocular defects) - dev't of congenital defects during this period is related to the concurrent dev't of the immune system, which mounts an antiviral immunoinflammatory response that may interfere w/ organogenesis - other congenital defects: hydrocephalus, cataracts/ retinal lesions, hypotrichosis, brachygnathism, arthrogryposis/ dwarfism

how is BVD virus transmitted?

- *persistently infected (PI)*: cattle that are infected for life & acutely infected are the major source of virus - horizontal transmission: ingestion, inhalation, venereal, blood - vertical transmission: transplacental (100% in PI dams) - indirect transmission via contaminated fomites/ personnel - virus can be isolated in most body fluids (saliva, urine, feces, nasal discharge, uterine fluid, semen, blood) & in high concentrations for PI animals

what are the different genotypes of the BVD virus (agent)?

- *type I (a & B), type II (a)* - genotypes determined in PCR - important when considering dz syndromes, dx testing & vax

what is the pathogenesis of BVD virus?

- BVDV causes dz in infected cattle by damaging epithelial tissues of the GI, integument, & respiratory tracts, & the lymphoid tissue thru-out the body - 1° viral replication occurs in the resp. tract & tonsils; from there, BVDV is disseminated to lymphoid tissue & epithelial surfaces thru-out the body, causing *lymphoid depletion* (--> immunosuppression) & epithelial *erosions*

what are the clinical signs of immunosuppression as a form of BVDV?

- BVDV targets B & T lymphocytes, neutrophils & macrophages - cell numbers & function are reduced by viral infection - mastitis, metritis, salmonellosis & pasteurellosis/ mannheimiosis may occur

what is the best test to do for screening for PI cattle?

- ELISA (antigen capture w/ ear notch/ skin biopsy)

how is BVD virus introduced into a herd?

- PI animals - PI fetus - acutely infected animals w/in 2-3 wks of active dz - fence line contact - wild ruminants

how is BVD virus maintained within a herd?

- PI animals - cycling of virus in acutely infected cattle

what is the pathogenesis of transplacental NCP BVDV infection btwn 50-125 days of gestation?

- abortion (1st trimester) - fetal mummification - development of *immunotolerant PI animal* - viral antigens are programmed to be recognized as "self"

how is BVDV treated?

- antibiotics - supportive care (fluids, NSAIDs, transfusions)

how is BVDV prevented?

- biosecurity - vaccination (MLV more efficacious - both CM & humoral immunity) - prevent viremia in dam to protect fetus - breeding animals usually vaccinated w/ MLV at 6 mo., 1 yr, & annually prior to breeding

what are the clinical signs of the hemorrhagic syndrome/ "bleeder syndrome" form of BVDV?

- characterized by fever thrombocytopenia, bloody diarrhea, epistaxis, hemorrhages on mucosal surfaces, hyphema, bleeding from injection sites, fever, leukopenia, death - thrombocytopenia (<25,000) & platelet dysfunction due to viral infection of megakaryocytes/ platelets - case fatality rate ~ 25%; survivors can recover & thrive, or remain unthrifty

what is the pathogenesis of transplacental NCP BVDV infection btwn 1-50 days of gestation?

- conception failure & early embryonic death (both --> repeat breeders) - PI & acutely infected bulls shed virus in semen for prolonged periods & may be source of infection - BVDV antigen has been shown in bovine ovaries in assoc. w/ oophoritis 60 days post experimental infection

what are the clinical signs of acute BVDV neonatal infections?

- congenital infections - calves w/ failure of passive transfer - BVD outbreak in herd or vax failure - *pneumonia & enteritis, often fatal* - rare in well-vaccinated herds

what are the clinical signs of acute mucosal dz

- depression, complete anorexia, rumen stasis - fever (104-105), increased heart & resp rates - profuse, watery diarrhea, 2-4 days after onset of illness - foul-smelling feces, often containing mucus, blood, fibrin - leukopenia (neutropenia) (*acute endotoxic infections + neutropenia*) - oral lesions (*erosions*) - skin erosions (interdigital, coronitis) - progressive dehydration, electrolyte imbalance, 2° bacterial infections - death occurs 5-7 days after onset of clinical signs (due to electrolyte/ acid-base imbalance)

what are the clinical signs of acute BVDV infection?

- fever, leukopenia (neutropenia), depression, anorexia, oculonasal discharge, salivation, oral erosions, diarrhea, decreased milk production - skin lesions & coronitis are common

what is the causative agent of BVD virus?

- flaviridae - pestivirus - unstable in environment & susceptible to common disinfectants - important members of pestivirus genus include: BVDV, BDV (border dz virus), Hog Cholera (a FAD - not in USA)

what is the pathogenesis of transplacental NCP BVDV infection btwn 150-270 days of gestation (term)?

- infection during this time = *"congenital infections"* - *fetus mounts an immune response* (seropositive pre-colostrum) & clears the virus (normal live birth of a seropositive calf) - fetal infection causes *organ damage* prior to clearing of the infection resulting in late abortions, stillbirths, weak neonates & calves/ heifers w/ long term health effects - calves can be born normal, but then become seropositive upon suckling colostrum

what are the clinical signs of reproductive dz as a form of BVDV?

- infertility in bulls - infertility, repeat breeders, abortion, stillbirths & congenital anomalies in breeding females - *most common form of dz in endemic herds*

what are the clinical signs of respiratory dz as a form of BVDV?

- most common virus isolated from cattle dying of bovine resp dz - altho not a 1° resp pathogen, immunosuppressive effects compromise resp defenses - seroconversion to BVD common in beef calves experiencing shipping fever in feedlot, but not in dairy calves experiencing enzootic calf pneumonia

what are the necropsy findings in BVDV?

- similar in animals dying of mucosal dz & acute viral diarrhea - GI erosions, inflammation involving the mouth, esophagus, forestomachs, small intestine (esp. over Peyer's patches) & cecum - petechial/ ecchymotic hemorrhages, extensive GI tract hemorrhage seen w/ thrombocytopenic/ hemorrhagic syndrome - histologic lesions = necrosis of Peyer's patches, lymphoid destruction & small intestinal crypt necrosis

what are some characteristics of *acute mucosal dz* as a sequela to BVDV?

- sporadic dz affecting < 5% of herd - PI animals have dual infection w/ identical strains of NCP & CP virus - rarely, epizootics (outbreaks) may occur (more common in beef than dairy) - case fatality rate approaches 100% - incubation period = 10-14 days

infection w/ BVD virus is assoc. w/ a variety of distinct clinical syndromes:

- subclinical infection - immunosuppression - acute or peracute BVD (erosive gastroenteritis) - mucosal dz (severe erosive gastroenteritis - invariably fatal) - thrombocytopenia & hemorrhagic syndrome (more common in calves) - repro. failure

PI animals are the "heart and soul" of BVD; what does this mean?

- they see BVDV as "self" & therefore do not mount an immune response against the virus --> viral replication continues w/o restraint - remain persistently viremic, & therefore serve as important reservoir of infection for non-PI cattle thru-out their lives - they may appear clinically normal, or be small/ unthrifty for their age - if female PI animals live long enough & are able to conceive, the virus will be transmitted to developing fetus & calves are invariable PI as well

what is the pathogenesis of BVD in non-PI immunocompetent animals acutely infected with NCP BVDV?

- viral replication is inhibited by specific passive (colostrum) or acquired (vax or exposure) immunity - subclinical or mild infection = most common (70-90%) - (fever, leukopenia, seroconversion will usually be present) - may result in: *infertility* (viral replication in uterus/ ovaries); *acute BVD* (viral replication in the GIT; *thrombocytopenia* (viral replication in megakaryocytes --> decreased platelets & platelet function) - *immunosuppression (viral replication in lymphoid tissue)* - BVDV targets B & T lymphocytes, neutrophils & macrophages w/ cell numbers & function reduced

T/F: acute infection of BVDV in immunocompetent (non-PI) cattle is typically fatal

F (erosive gastroenteritis, similar to mucosal dz, but not fatal)

mucosal dz vs. acute dz: how can you tell if an animal is persistently infected & if treatment is warranted?

do ear notch test to differentiate: - acutely infected won't have enough virus in the skin to detect, while PI will

what is considered a "superinfection" w/ BVDV?

dual infection w/ NCP & CP BVDV (young PI animals (6 mo - 2 y) - acute mucosal dz - (due to spontaneous mutation of persistent NCP strain into identical CP virus) - chronic mucosal dz - viral re-assortment w/ vaccine or field strains to produce a CP strain near identical to persistent NCP strain

what kind of samples are used in *antigen detection* diagnostics for BVDV?

nasal swab, tissue biopsy, fetal tissue; ear notch works well (DFA, IHC, antigen capture ELISA)