The success story of BVD virus

Transcription

1 The success story of BVD virus BVD MD PI BVDV BVDV-1 BVDV-2 cp ncp Bovine Viral Diarrhea Mucosal Disease Persistently Infected Bovine Viral Diarrhea Virus Bovine Viral Diarrhea Virus Genotype 1 Bovine Viral Diarrhea Virus Genotype 2 cytopathic non-cytopathic BVD is a disease in cattle, which o is present all around the world o causes important economic losses o cannot be treated o can be prevented by vaccination and biosecurity o can be eradicated o is polymorphic o affects immune system o affects reproductive system o affects respiratory system o can be severe o can be soft o causes individual illness o affects herd health o has two main transmission ways o needslab testsfordiagnosis o has generated a lot of mythes in the mind of people o affects digestive tract 1

2 Thanks to Joe Brownlie 2008 Royal Veterinary College The two strategies of BVDV hit & run infect & persist Transient Infection Persistent Infection Hit & run - Acute transient infection infection virus clearance circa 3 weeks virus replication & shedding neutralizing Ab Transient Infection becomes immune BVDV Clinically symptomless Animal transiently infected Severe symptoms Horizontal infection of a naive animal, leads to clinical or subclinical infection, and to seroconversion 2

3 Infect & persist - persistent infection Infection in utero birth lifelong virus replication and shedding Birth of a PI calf BVDV NCP strain in early pregnancy Cow and calf infected Only dam becomes immune Calf born persistently infected (PI) Pathogenesis of horizontal, acute, transient infection virus sheding by infected animal through secretions and excretions contamination of fellow animal and oro-nasal infection local replication viremia virus spread to organs - lymphatic system - respiratory tract - digestive tract - reproductive tract pathology according to organ either death or seroconversion and virus clearence Pregnant or not pregnant? DURATION ±3 WEEKS 3

4 Ways of transmission Horizontal transmission by direct contact or indirectly through contaminated feed, water, trucks, and equipments BVDV is shed by viremic animals in body fluids, secretions and excretions BVDV penetrates into animals by oral and nasal way Vertical transmission In pregnant viremic animals BVDV can cross the placenta and infect the fetus BVD general signs BVD respiratory symptoms 4

5 BVD digestive symptoms BVD reproductive signs NOT BVD Reproductive effects of BVD Embryonic death Effects on ovary Failure of conception Conception Foetal death and abortion days 150 days Birth Breeding PI Development Immune system not yet mature Developmental defects Organogenesis Survival of antibody positive foetus 5

6 Protean storyline of BVDV infection There is no pathognomic symptom, and no consistent clinical picture BVD is a herd condition, and in each herd the picture is different, and not all signs are present in each herd BVDV is a team player, in association with other pathogens Infection leads to a higher incidence of further diseases, due to immunosuppresive properties of BVDV Something is wrong - blunted treatments Approach per barn Herd s clinic Calves in utero Born calves Young stock Direct effect Stillbirth Malformation PI Weak calves Scour Immunosuppression BRD Bloody diarrhea Immunosuppression Herd s clinic Perinatal mortality High neonatal mortality Increased morbidity (diarrhea, omphalitis, pneumonia) Blunted treatments Cough Blunted treaments Inhomogeneous groups Death Poordoers Cow s health Fever and depression Bloody diarrhea Interdigital ulcera Immunosuppression Drop in milk Mastitis Increased SCC Lameness Blunted treatments Cow s repro Oophoritis Salpingitis Fetal infection Repeat breeding Early embryonic death Abortions Retained placenta Humoral immunology of BVD 6

7 Hit & run - Acute transient infection infection virus clearance circa 3 weeks virus replication & shedding neutralizing Ab Infect & persist - persistent infection Infection in utero birth lifelong virus replication and shedding BVD-Virus: Genome Organisation structural proteins N pro C E rns E1 E2 p7 NS2-3 NS4A NS4B NS5A-B 5 NTR IRES P80 = NS3 NS2 NS3 NS5A NS5B P120 = NS2 3 (121;125) NS = non structural cp: overexpressed E = envelope 3 NTR 7

8 Transient infection and seroconversion infection virus clearance circa 3 weeks virus replication protein p80 = Ag neutralizing Ab p80 Ab Diagnostic tests for detection virus virus isolation, PCR Ab ELISA Ab, SNT=VN p80 Ag ELISA p80 Ag p80 Ab ELISA p80 Ab Persistent infection, no seroconversion Infection in utero birth 1 st sampling 2 nd sampling 3 weeks virus replication protein p80 = Ag Diagnostic tests for detection virus p80 Ag virus isolation, PCR ELISA p80 Ag Quiz status of an animal serology virology animal NEG POS NEG NEG naive Seroconverted by natural infection or by vaccination or passive = colostrum NEG POS TI or PI TI before seroconversion or PI POS POS TI TI after seroconversion but before virus eliminitation 8

9 BVD-Virus: cytopathic or non-cytopathic? structural proteins N pro C E rns E1 E2 p7 NS2-3 NS4A NS4B NS5A-B 5 NTR IRES P80 = NS3 NS2 NS3 NS5A NS5B P120 = NS2 3 (121;125) NS = non structural cp: overexpressed E = envelope 3 NTR Mucosal Disease BVDV NCP in early pregnancy Only dam becomes immune Cow and calf infected Calf born persistently infected (PI) Superinfection with second BVDV biotype CP Fatal Mucosal disease BVD MD Mucosal Disease 9

10 Etiology BVDV - Bovine Viral Diarrhea Virus Family: Flaviviridae Genus: Pestivirus Genotypes: BVDV 1 & BVDV 2 Subtypes: BVDV 1a -, BVDV 2a - new subtypes may come up Biotypes: ncp non-cytopathic & cp cytopathic ssrna, 11 or 12 proteins, 5 structural and 6 (7) non structural icosahedron capsid & envelope Conclusion BVDV spreads within the cattle population by horizontal acute infection, and by vertical infection leading sometimes to persistent infection. It leads to a protean and fuzzy clinical picture within the herd, ranging from an invisible infection to severe disease and death. It is often associated with other pathogens, and belongs to the differential diagnostic of general conditions (fever, petechiae, bleeding, erosions on mucosae, ulcera, lameness), of BRD (DD: adenovirus, reovirus, PI3, IBR, RSV, mannheimia haemolytica, aso ), of diarrhea (DD: rotavirus, coronavirus, e. coli, salmonella spp, cryptosporidium parvum, giardia, aso ), and of reproductive disorders (retained placenta, repeat breeding, abortion, malformation, aso ). PIs are the corner stone of infection and control of BVDV. BVDV lives at it s host s expense, and always hurts the infected cattle and the whole herd as well, and leads to economic losses. BVD eradication includes: - herd vaccination to block virus circulation - identification and removal of all PIs within a short period 10