Bovine Coronavirus

Pathogenesis

Bovine enteriMalabsorptive diarrhoea

Villus stunting in small intestine and colon
Associated with calf scour

Epidemiology

Endemic worldwide
Calf coronavirus may contribute to Enzootic pneumonia of calves
May be associated with Winter dysentery in cattle

Control

No calf vaccines available
Some dam vaccines available to elevate and prolong passive immunity

DATASHEET containing DISEASE first then VIRUS below references

Animal Health and Production Compendium

Selected sections for: bovine coronavirus infection Identity Pathogen/s Overview Distribution Distribution Table Hosts/Species Affected Host Animals Systems Affected List of Symptoms/Signs Epidemiology Zoonoses and Food Safety Pathology Diagnosis Disease Course Disease Treatment Table Disease Treatment Vaccines Prevention and Control References Images

Datasheet Type(s): Animal Disease Identity

Preferred Scientific Name bovine coronavirus infection

International Common Names

English BCV infection, bovine coronavirus-associated enteritis, bovine coronavirus-associated respiratory disease, bovine coronavirus-associated shipping fever, bovine viral scours, bovine winter dysentry, calf diarrhoea, calf viral diarrhoea, coronaviral enteritis of calves, coronaviral scours, coronavirus infection in calves and cattle, epizootic diarrhoea, infectious diarrhoea, neonatal calf diarrhoea, neonatal diarrhoea, reo-coronavirus calf diarrhoea, scours, winter dysentery, winter dysentery in cattle, winter haemorrhagic enteritis, winter scours

Pathogen/s

bovine coronavirus

Overview Bovine coronavirus (BCV) was characterized as a viral cause of calf enteritis by Mebus et al. (1973) and is now recognized as a leading cause of calf enteritis around the world. The virus infects the enteric and/or upper respiratory tract of calves that are 1-week to 3-months-old. In adult animals, the disease is usually sub-clinical, and the virus may be excreted intermittently at low titre (Schoenthaler and Kapil, 1999). Bovine coronavirus has also been identified as the etiological agent of winter dysentery in adult cows (Saif, 1990). The incidence of BCV varies in different parts of the world but published and annual reports indicate that BCV causes 15-30% of calf enteritis cases (Langpap et al., 1979). The incidence of diarrhoea from bovine coronavirus may be underestimated because many laboratories around the world are not equipped with BCV antigen detection methods such as electron microscopy and BCV ELISA; also the isolation of BCV in tissue culture is difficult (Kapil et al., 1996). Bovine coronavirus infection occurs in combination with other enteric viral, bacterial, parasitic, and protozoal pathogens. Other than enteric infection and sporadic respiratory infections, BCV is not associated with any other system/disease in cattle. Based on published reports, bovine coronavirus does not produce disease in humans.

Distribution Bovine coronavirus has a worldwide distribution and has been reported on six continents. Major antigenic characteristics are shared among isolates around the world; however, minor antigenic variations may be found among BCV isolates from different areas. European BCV isolates are antigenically similar to the American BCV isolates (Woode et al., 1978).

Distribution Table

Country Distribution Last Reported Origin First Reported Invasive References Notes ASIA China Present Lu et al., 1991

-Liaoning Present Li et al., 1996

Indonesia Present Putra & Della, 1985

Japan Present Taniguchi S(et al), 1986; Fukutomi et al., 1999

Korea, Republic of Present Chung et al., 1997; Lee et al., 1995

Thailand Present Aiumlamai et al., 1992

Turkey Present Alkan, 1998

AFRICA Ethiopia Present Abraham et al., 1992

Nigeria Present Baba et al., 1994

NORTH AMERICA Canada

-Alberta Present Carman & Hazlett, 1992

-Quebec Present Ganaba et al., 1995; Dea et al., 1995

USA Present Storz et al., 1996; Kapil et al., 1999

-Ohio Present Heckert et al., 1990; Smith et al., 1998

SOUTH AMERICA Argentina Present Panighi et al., 1992; Pinto et al., 1993

Suriname Present Corbett et al., 1989

EUROPE Albania Present Ikonomi & Dino, 1994

Belgium Present Broes et al., 1984

Czechoslovakia (former) Present Krpata, 1985; Krupicka, 1990

Denmark Present Tegtmeier et al., 1999; Woode et al., 1978

France Present Laval et al., 1986; Bendali et al., 1999

Germany Present Jiménez et al., 1989; Anders, 1996

Italy Present Straub & Trenti, 1994

Russian Federation

-Russia (Asia) Present Koromyslov et al., 1984; Sokolova et al., 1987

-Russia (Europe) Present Koromyslov et al., 1984; Sokolova et al., 1987

Spain Present Alvarez et al., 1987; De et al., 1998

Sweden Present Larsson et al., 1991; Tråvén et al., 1999

Switzerland Present Battaglia et al., 1986; Läuchli et al., 1990

United Kingdom Present Paton et al., 1998; Derbyshire & Brown, 1978

OCEANIA Australia Present Bürki, 1985

New Zealand Present Horner, 1977

Hosts/Species Affected All breeds of cattle are hosts for BCV. There is no known cattle breed that is resistant to the disease. However, animals may differ in their susceptibility, which might be controlled by the number of receptors in the intestinal epithelium. Interaction between the viral spike glycoprotein (anti-receptor) and a specific carbohydrate receptor is essential for viral infectivity. The carbohydrate receptor used by bovine coronaviruses for viral attachment is N-acetyl-9-O-acetylneuraminic acid (Schultze and Herrler, 1992). Wild ruminants are also infected with the virus. Even though wild ruminant coronavirus may be antigenically, genetically, and biologically very close to coronaviruses, it is an accepted rule that a coronavirus isolated from any species is named after that host. Elk coronavirus has been found to be related closely to BCV both genetically (Majhdi et al., 1997) and antigenically (Daginakatte et al., 1999). Distinguishing between different BCV isolates with monoclonal antibodies is difficult. Most BCV isolates and wild ruminant strains can be distinguished on the basis of a haemagglutination inhibition test using mouse erythrocytes. The differences between strains also lie in the haemagglutinin-esterase genes (Crouch et al., 1985). The haemagglutinin gene facilitates haemagglutination and esterase activities, both of which can differ among BCV isolates. The haemagglutinin-esterase gene may have been acquired by coronaviruses during evolution from influenza viruses by random recombination events. A vaccine against BCV might protect against heterologous infection in other ruminants.

Host Animals

Animal name Context Bos indicus (zebu) Bos taurus (cattle)

Capreolus capreolus Domesticated host, Wild host Cervus elaphus (red deer) Domesticated host, Wild host

Systems Affected

Digestive - Large Ruminants Digestive - Small Ruminants Respiratory - Large Ruminants Respiratory - Small Ruminants

List of Symptoms/Signs

Sign Life Stages Type Digestive Signs Melena or occult blood in faeces, stools Sign [C] Palpable dilated bowel internal paplation Sign [C] Increased borborygmi, gut sounds Sign [C] Dark colour stools, faeces Sign [C] Mucous, mucoid stools, faeces Sign [C] Excessive salivation, frothing at the mouth, ptyalism Sign [C] Rumen hypomotility or atony, decreased rate, motility, strength Sign [C] Ping right side, auscultable gas filled viscus Sign [C] Anorexia, loss or decreased appetite, not nursing, off feed C2 ( Calf ) Sign [C] Bloody stools, faeces, haematochezia C2 ( Calf ) Sign [C] Diarrhoea C2 ( Calf ), C3 ( Heifer ), C4 ( Cow ) Sign [C] Mucous, mucoid stools, faeces Sign [C] General Signs Dehydration C2 ( Calf ) Sign [C] Lack of growth or weight gain, retarded, stunted growth C2 ( Calf ) Sign [C] Weight loss C2 ( Calf ) Sign [C] Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift C2 ( Calf ) Sign [C] Generalized weakness, paresis, paralysis Sign [C] Fever, pyrexia, hyperthermia Sign [C] Polydipsia, excessive fluid consumption, excessive thirst Sign [C] Generalized weakness, paresis, paralysis Sign [C] Inability to stand, downer, prostration Sign [C] Nervous Signs Dullness, depression, lethargy, depressed, lethargic, listless C2 ( Calf ) Sign [C] Pain/Discomfort Signs Colic, abdominal pain Sign [C] Reproductive Signs Agalactia, decreased, absent milk production Sign [C] Respiratory Signs Purulent nasal discharge Sign [C] Coughing, coughs Sign [C] Dyspnea, difficult, open mouth breathing, grunt, gasping Sign [C] Increased respiratory rate, polypnea, tachypnea, hyperpnea Sign [C] Mucoid nasal discharge, serous, watery C2 ( Calf ) Sign [C] Abnormal breathing sounds of the upper airway, airflow obstruction, stertor, snoring C2 ( Calf ) Sign Abnormal lung or pleural sounds, rales, crackles, wheezes, friction rubs C2 ( Calf ) Sign [C] Urinary Signs Polyuria, increased urine output Sign [C]

Epidemiology The primary routes of entry for bovine coronavirus are through the mouth or nasal cavity (Clark, 1993). Adult cattle are carriers and excrete the virus at low titre; however, during parturition, cows shed higher titres of the virus. It is possible that increased levels of progesterone and other hormones play a role in amplifying the viral titre and thus increase the chances of transmission (Crouch et al., 1985). Close contact between dam and offspring increases the chance of viral transmission because the calf has an immature immune system. The hindquarters of dams should be hosed in order to minimize faecal transmission of the virus to calves. Cleanliness of the maternity pens is extremely important. Even though cows are considered to be the source of BCV for calves, the prolonged excretion of BCV in calves indicates that these calves may be another possible source of the virus for other calves that become clinically sick (Kapil et al., 1990). Although BCV is sensitive to environmental conditions such as sunlight, heat, lipid solvents, and disinfectants, coronaviral scours may occur in a herd year-after-year. The virus can survive in organic material, such as soiled hay, for long periods of time, especially during winter months. Delivery of beef calves in pasture under extreme winter conditions might increase the chances of disease because of depression in the immune system, stress, and greater survival of virus due to lower ambient temperatures. Animals will also be more susceptible to infection with the feeding of colostrum that does not contain sufficient amount of BCV-specific antibody or if a calf is not able to suckle and obtain colostrum. Arthropod or small mammal vectors of the disease are not known. However, BCV and other ruminant coronaviruses are related antigenically; wild ruminants such as deer, water buck, wild antelopes and bison may play a role in the transmission of the disease (Tsunemitsu et al., 1995). In areas of the world where wildlife and domestic cattle share common pastures, infection may cross among these species. Thus, transmission is due to direct or indirect contact. Animals are more susceptible to BCV during periods of long travel when they are in close contact. Therefore, BCV has been recognized as a cause of shipping fever (Storz et al. 1996).

Zoonoses and Food Safety Although bovine coronavirus is not zoonotic, human coronaviruses exist that are related antigenically. There is a single report on the possible transmission of BCV from an experimentally infected calf to a human investigator; however, this information was anecdotal (Storz and Rott, 1981). Bovine coronavirus is not transmitted through meat or any other food sources.

Pathology Bovine coronavirus antigen is present in the epithelial lining of the villi, the crypts and in the nasal glands and nasal epithelium. Occasionally, an isolated macrophage is seen in the lamina propria and in the Peyer’s patches (Zhang et al., 1997). This indicates that although the virus may be distributed by macrophages, it probably does not infect other parts of the body. Haemorrhages, enlargement of Peyer’s patches and fluid diarrhoea are evident upon examination of infected animals. Immunohistochemistry with BCV-specific monoclonal antibodies was used to study the pathology of BCV. A monoclonal antibody (Z3A5) was developed and found to be highly specific for detection of BCV spike protein in paraffin-embedded, formalin-fixed intestines (Zhang et al., 1997). A monoclonal antibody (8F2) against the nucleoprotein of coronavirus can also be used (Daginakatte et al., 1999). Anti-nucleoprotein monoclonal antibodies are more sensitive in ruminant coronavirus detection than the anti-spike protein monoclonal antibodies, because the nucleoprotein accounts for the major viral protein in BCV-infected cells.

Diagnosis Enteric BCV infections generally are diagnosed by examination of faecal samples or intestinal contents. When faecal samples are submitted to laboratories, BCV is diagnosed by direct electron microscopy (EM) or antigen capture ELISA. If intestinal contents are submitted, then the test of choice is direct EM. The virus has a mean diameter of 126 nm as determined by transmission EM. A double-ring of surface proteins is evident. Other enteric viral agents (such as Rotavirus, Parvovirus, Bredavirus, and Adenovirus) could be present along with the bovine coronavirus infection and also be detected. However, routine use of electron microscopy for testing is tedious, needs trained assistance, requires an expensive microscope and lacks sensitivity. The technique can be improved using immuno-electron microscopy (Saif et al., 1991). In addition, ELISA may be used to detect viral antigen and is highly sensitive and specific. Kansas State University, USA, has developed a BCV-specific ELISA. The sensitivity of this ELISA is 104 BCV particles per ml of 10% faecal suspension. Compared to EM, this BCV ELISA had 96% specificity (Schoenthaler and Kapil, 1999). In addition, a bovine coronavirus antigen test kit is available commercially from Syracuse Bioanalytical, Ithaca, New York, USA. No diagnostic tools are available for cow-side testing or in-office testing for veterinarians. When sending samples to diagnostic services it is important to include at least five sections from different parts of the gut, including the spiral colon because this is the common site of virus persistence (Kapil et al., 1994a; Kapil et al., 1994b). Sometimes BCV infections are focal and are easy to miss if only a few sections are examined. In remote areas of the world where diagnostic services are not easily accessible, the gut can be cut into 5 cm pieces, the ends tied and sent (on dry ice or ice packs) to the nearest diagnostic laboratory for fluorescent antibody or EM analysis. Enteric viral agents are common in most ruminant animals. Every animal is exposed to BCV within a lifetime and the serological incidence of BCV is close to 100%. They may or may not develop the disease depending on the level of age susceptibility (Torres-Medina et al., 1985). In respiratory coronavirus disease the viral antigen can easily be demonstrated in washed nasal epithelial cells by direct fluorescent antibody test using conjugate obtained from National Veterinary Services Laboratory (Kapil et al., 1991). Demonstrating the antigen in the lower respiratory tract is difficult. In the future, diagnosis could be made more specific, if antibodies against spike protein (protective antigen) are monitored through a sub-unit ELISA. Serological tests, such as indirect fluorescent antibody, are used to monitor the presence of antibody in colostrum, serum, and intestinal contents. However, these are not yet commercially available; the Kansas State University Diagnostic Laboratory, USA conducts such tests. Of equal significance is the performance of direct fluorescent antibody technique for diagnosis of the virus in tissue sections (Mebus et al., 1973). A tendency for autofluorescence because of the presence of mucus could give misleading results; however, these problems are rare in incidence. Primary isolation of BCV in tissue culture is difficult. It can grow by serial passage in continuous cell lines e.g. Vero, MDBK, and porcine kidney cell lines. A cytopathic effect is clearly evident at the second and third passages. Treatment of cells with trypsin (20 µl/ml) increases the production of BCV in cell culture (Dea et al., 1980). The protective immune responses against BCV occur on mucosal surfaces; serum antibodies do not provide any protection. The levels of immunoglobulins (IgM, IgA, IgG1, and IgG2) differ depending on the level of bovine coronaviral antigen in different regions of the gut (Kapil et al., 1994a; Kapil et al., 1994b). The role of cell-mediated immunity in BCV has not been well characterized. The absorption of colostral antibodies occurs in an open gut for up to 24 hours after birth. Thus, colostrum having a high titre for BCV and other enteric viral agents should be fed within this period. If the calf does not receive a sufficient amount of colostrum during this time it becomes extremely susceptible not only to enteric diseases but to other perinatal diseases such as pneumonia. Diarrhoea and pneumonia are the major causes of death in calves.

Disease Course Bovine coronavirus causes both acute and chronic disease. Most calves suffer from acute infection, but in later stages calves may periodically shed the virus. Adult cattle have only chronic BCV infection. Incubation time is about 20 hours, and symptoms appear at around 24 hours after experimental infection (Kapil et al., 1990). After 3-4 days of viral excretion at high titre, the titre level falls dramatically. Therefore, samples should be collected during early stages of the disease. Tests, such as electron microscopy, that lack sensitivity will miss a positive diagnosis if samples are taken in later stages of infection. Approximately 50,000 virus particles per gram of faeces should be present to detect the virus by EM (Flewett, 1978). Clinically normal cattle in contact with calves showing BCV signs should also be sampled, because they may be in the early stage of disease and will be secreting high amounts of virus. It is preferable to submit two pools of faecal samples from acutely affected (clinically infected) and contact animals (clinically normal) for testing by EM. BCV antigen can be detected in approximately 25% of calves affected by BCV-associated disease in the respiratory tract but not in the intestinal tract (respirotropic isolates). In another 25% of affected calves, BCV can be detected only in the intestinal tract but not in the respiratory tract (enterotropic isolates). In the remaining 50% of animals, BCV antigen can be demonstrated in both enteric and respiratory tracts (pneumoenteric isolates) (Kapil and Goyal, 1995). Isolates of BCV produce enteric disease and isolates of bovine respiratory coronavirus produce both enteric and respiratory coronavirus disease. Most isolates of BCV are either enterotropic or pneumoenteric. There is very limited evidence that indicates that purely respiratory tropic strains exist. Respiratory and enteric diseases in calves and cattle may be different manifestations of the same virus at different stages of infection. On the basis of experimental infection, the pneumoenteric affected calves suffer first from enteric infection and then later with respiratory infection (Kapil et al., 1991). Virus infection of the enteric tract starts in the small intestine and spreads to the large intestines. Rarely, mild fibrinonecrotic typhlocolitis is recognized. Exfoliation of epithelium and microerosions may be seen. The extent of lesions depends on the severity and duration of infection. The lamina propria may be moderately infiltrated with mononuclear inflammatory cells. Necrosis of cells in mesenteric lymph nodes is associated with viral replication. Peyer’s patches in animals examined after 4 or 5 days of clinical infection often appear involuted. After infected epithelial cells die they are replaced by immature cells, severely diminishing the absorption in the gut. Immature cells are also unable to secrete normal amounts of digestive enzymes. This decrease in absorbant and digestive ability leads to metabolic imbalance. Diarrhoea causes dehydration, acidosis, and hypoglycaemia. If uncontrolled, calves may die of acute shock and heart failure. However, calves may recover from infection because the virus rarely attacks crypt epithelial cells. These epithelial cells produce cells that are virus-resistant and replace damaged cells (Clark, 1993). Bovine coronavirus resulting in respiratory disease is more than likely transmitted by aerosols. After initial infection of the nasal epithelium, the virus is swallowed along with saliva, subsequently affecting the intestinal tract. Calves develop nasal discharge, cough, laboured breathing, and fever of up to 41C due to dehydration and metabolic imbalance. Respiratory distress may result from metabolic effects of the disease due to extreme dehydration. In calves there is extreme respiratory distress followed by death. Based on experimental studies, ventral parts of the lungs are involved (Kapil et al., 1991). Respiratory coronavirus lesions are atelectasis, interstitial pneumonia, emphysema, haemorrhage, and presence of antigen in the nasal cavity, nasal glands, and upper one-third of the trachea. Bovine coronavirus has been consistently identified as the primary pathogen in faeces of cows with winter dysentery. Many characteristics of winter dysentery closely coincide with the traits of BCV infection. Disease outbreaks usually occur during the winter months; cows that are pregnant or recently calved are most frequently affected. Faecal and respiratory transmission of coronavirus could account for outbreaks of winter dysentery in confined cattle (Saif, 1990). A severe drop in milk production and haemorrhagic diarrhoea characterizes winter dysentery.

Disease Treatment Table

Drug Dosage, administration and withdrawal times Life stages Adverse affects Drug resistance Type Calf-guard, BCV modified live vaccine (Pfizer)® Rehydrate lyophilized vaccine with sterile diluent provided and administer without delay. 3 ml dosage for both calves and cows. Withdrawal time after 21 days. Calf/Cow/Heifer No Vaccine intravenous fluids Warm solution to body temperature and administer according to body weight of animal and state of dehydration or diarrhoea. Calf overhydration No Drug oral electrolytes Warm solution to body temperature and administer according to body weight of animal and state of dehydration or diarrhoea. Calf overhydration No Drug scour-bos 4, BCV killed vaccine, Grand Labs Administer 2 ml intramuscularly 8-10 weeks prior to calving. Repeat in 6 weeks. Revaccinate with one dose 8-10 weeks prior to each subsequent calving. Cow/Heifer No Vaccine scour-bos 6 BCV, C. perfringens, E. coli Administer 2 ml intramuscularly. The first year a booster dose of scour-bos 4 should be given for complete viral coverage. Calf/Cow/Heifer No Vaccine scour-guard 3, BCV killed vaccine, Pfizer Calf vaccination: orally administer as soon as possible after birth. Cow vaccination: administer two intramuscular doses 3-6 weeks apart during late pregnancy. Ideally, the second dose should be administered within 30 days prior to calving. Cows should be revaccinated with two doses during each subsequent pregnancy. Withdrawal time is 21 days. Calf/Cow/Heifer No Vaccine

Disease Treatment Treatment of BCV is generally symptomatic. Fluid therapy is given orally or intravenously. Astringents also are used to control diarrhoea. Additional feeding of fortified colostrum may be useful in preventing the clinical disease in newborn calves (Murakami et al., 1986). It is suggested that milk containing high amounts of coronavirus-specific antibodies be fed to calves for the first 14 days of life to reduce the incidence and duration of viral shedding (Heckert et al., 1991). Addition of the neutralizing monoclonal antibody (Z3A5) against the spike protein to immune colostrum might also provide protection, but it is not yet commercially available. It has also been reported that in vitro Hygromycin B inhibits the replication of virus in cell culture (Zhang et al., 1997); however, the drug has not been tested in calves.

Vaccines

Vaccine Dosage, Administration and Withdrawal Times Life Stages Adverse Affects Calf-guard, BCV modified live vaccine (Pfizer)® Rehydrate lyophilized vaccine with sterile diluent provided and administer without delay. 3 ml dosage for both calves and cows. Withdrawal time after 21 days. scour-bos 4, BCV killed vaccine, Grand Labs Administer 2 ml intramuscularly 8-10 weeks prior to calving. Repeat in 6 weeks. Revaccinate with one dose 8-10 weeks prior to each subsequent calving. scour-bos 6 BCV, C. perfringens, E. coli Administer 2 ml intramuscularly. The first year a booster dose of scour-bos 4 should be given for complete viral coverage. scour-guard 3, BCV killed vaccine, Pfizer Calf vaccination: orally administer as soon as possible after birth. Cow vaccination: administer two intramuscular doses 3-6 weeks apart during late pregnancy. Ideally, the second dose should be administered within 30 days prior to calving. Cows should be revaccinated with two doses during each subsequent pregnancy. Withdrawal time is 21 days.

Prevention and Control On the basis of field trials and experimental trials the vaccines available so far are generally non-effective (Thurber et al., 1977). To be effective, vaccination must be given immediately at birth, before colostrum and possible infection with field virus. Levels of coronavirus antibodies in colostrum may inactivate the vaccine. Also, colostrum from dams is only secreted for 3-5 days after birth and is replaced by milk, which contains little antibody. Colostrum antibody only remains in calf intestine for approximately 2 days. Thus, at 5-7 days after birth there is little coronavirus protection in the intestine even though the calf may present high anti-coronavirus titres in serum. Administration of immune colostrum can be continued for further protection. Antigenic variation among BCV isolates and the inability of the vaccine to replicate sufficiently in the calf intestine may also lead to lower vaccine efficacy.

References

Abraham G, Roeder PL, Zewdu R, 1992. Agents associated with neonatal diarrhoea in Ethiopian dairy calves. Tropical Animal Health and Production, 24(2):74-80; 15 ref.

Aiumlamai S, Alenius S, Nithichai K, 1992. Prevalence of antibodies to various bovine viruses in bulk tank milk samples from dairy herds in the Muaglek area. Thai Journal of Veterinary Medicine, 22(2):113-119; 14 ref.

Alkan F, 1998. The role of Rotavirus and Coronavirus in calf diarrhoea. Veteriner Fakültesi Dergisi, Ankara üniversitesi, 45(1):29-37; 33 ref.

Alvarez M, Rubio P, Cármenes P, 1987. Prevalence of bovine coronavirus infection in Northeast Spain. Study of the incidence and diffusion of the infection in veal calf units. Medicina Veterinaria, 4(3):159-161, 163-165; 24 ref.

Anders C, 1996. Phenotype and genotype of field isolates of bovine coronavirus, 1986-1992. Phänotypische und genotypische Untersuchungen an bovinen Coronavirus-Feldisolaten aus den Jahren 1986 bis 1992., 93 pp.; 23 pp. of ref.

Baba SS, Bobbo AG, Akoma MB, Osiyemi TI, 1994. Slaughterhouse survey for antibodies against selected viruses in ruminant sera in Maiduguri, Borno State, Nigeria. Tropenlandwirt, 95(April):55-62; 14 ref.

Battaglia M, Lutz H, Wyler R, 1986. Serological survey on the occurrence of bovine coronavirus in Switzerland. Schweizer Archiv für Tierheilkunde, 128(4):213-218; 28 ref.

Bendali F, Bichet H, Schelcher F, Sanaa M, 1999. Pattern of diarrhoea in newborn beef calves in south-west France. Veterinary Research, 30(1):61-74; 26 ref.

Broes A, Opdenbosch Evan, Wellemans G, 1984. Isolation of a coronavirus from Belgian cattle with winter haemorrhagic enteritis. Annales de Médecine Vétérinaire, 128(4):299-303; 14 ref.

Bürki F, 1985. Diagnosis, prevalence and prophylaxis of the principal viral causes of calf diarrhoea. Wiener Tierärztliche Monatsschrift, 72(12):373-377; 17 ref.

Carman PS, Hazlett MJ, 1992. Bovine coronavirus infection in Ontario, 1990-1991. Canadian Veterinary Journal, 33(12):812-814; 10 ref.

Chung ChungWon, Cho JaeJin, Cho InSoo, An SooHwan, Jang MiSun, 1997. Isolation and characterization of bovine coronavirus from calves and adult cows with diarrhoea. RDA Journal of Veterinary Science, 39(2):11-18; 23 ref.

Clark MA, 1993. Bovine coronavirus. British Veterinary Journal, 149(1):51-70; many ref.

Corbett WT, Guy J, Lieuw-A-Joe R, Hunter L, Grindem C, Levy M, Cullen J, Vaz V, 1989. Epidemiological survey of cattle diseases in Surinam. Boletín de la Oficina Sanitaria Panamericana, 106(4):314-320; 6 ref.

Crouch CF, Bielefeldt Ohmann H, Watts TC, Babiuk LA, 1985. Chronic shedding of bovine enteric coronavirus antigen-antibody complexes by clinically normal cows. J. Gen. Virol., 66:1489-500.

Daginakatte GC, Chard-Bergstrom C, Andrews GA, Sanjay Kapil, 1999. Production, characterization, and uses of monoclonal antibodies against recombinant nucleoprotein of elk coronavirus. Clinical and Diagnostic Laboratory Immunology, 6(3):341-344; 15 ref.

De la Fuente R, Garcia A, Ruiz-Santa-Quiteria JA, Luzon M, Cid D, Garcia S, Orden JA, Gomez-Bautista M, 1998. Proportional morbidity rates of enteropathogens among diarrhoeic dairy calves in central Spain. Prev. Vet. Med., 36:145-52.

Dea S, Michaud L, Milane G, 1995. Comparison of bovine coronavirus isolates associated with neonatal calf diarrhoea and winter dysentery in adult dairy cattle in Québec. Journal of General Virology, 76(5):1263-1270; 32 ref.

Dea S, Roy RS, Begin ME, 1980. Physicochemical and biological properties of neonatal calf diarrhoea coronaviruses isolated in Quebec and comparison with the Nebraska calf coronavirus. Am. J. Vet. Res., 41:23-29.

Derbyshire J, Brown EG, 1978. Isolation of animal viruses from farm livestock waste, soil and water. J. Hyg., 81(2):295-302.

Flewett TH, 1978. Electron microscopy in the diagnosis of infectious diarrhoea. J. Am. Vet. Med. Assoc., 173:538-541.

Fukutomi T, Tsunemitsu H, Akashi H, 1999. Detection of bovine coronaviruses from adult cows with epizootic diarrhea and their antigenic and biological diversities. Archives of Virology, 144(5):997-1006; 32 ref.

Ganaba R, Bélanger D, Dea S, Bigras-Poulin M, 1995. A seroepidemiological study of the importance in cow-calf pairs of respiratory and enteric viruses in beef operations in Northwestern Quebec. Canadian Journal of Veterinary Research, 59(1):26-33; 37 ref.

Guy JS, Brian DA, 1979. Bovine coronavirus genome. J. Virol., 29:293-300.

Heckert RA, Saif LJ, Hoblet KH, Agnes AG, 1990. A longitudinal study of bovine coronavirus enteric and respiratory infections in dairy calves in two herds in Ohio. Veterinary Microbiology, 22(2/3):187-201; 35 ref.

Heckert RA, Saif LJ, Myers GW, Agnes AG, 1991. Epidemiologic factors and isotype-specific antibody responses in serum and mucosal secretions of dairy calves with bovine coronavirus respiratory tract and enteric tract infections. American Journal of Veterinary Research, 52(6):845-851; 44 ref.

Horner GW, 1977. Some recent virus isolations and their importance in New Zealand. New Zealand Veterinary Journal, 25(11):335-336.

Ikonomi R, Dino L, 1994. Detection of bovine coronavirus as causative agent of diarrhoea in newborn calves. Bujqësia Shqiptare, No. 2:15-17; 13 ref.

Jiménez C, Herbst W, Biermann U, Müller JM, Schliesser T, 1989. Isolation in cell culture of coronaviruses from nasal swab samples from calves with respiratory disease in the German Federal Republic. Journal of Veterinary Medicine. Series B, 36(8):635-638; 22 ref.

Kapil S, Goyal SM, 1995. Bovine coronavirus - associated respiratory disease. Compendium on Continuing Education for the Practicing Veterinarian, 17(9):1179-1181; 16 ref.

Kapil S, Goyal SM, Trent AM, 1994. Cellular immune status of coronavirus-infected neonatal calves. Comparative Immunology, Microbiology and Infectious Diseases, 17(2):133-138; 16 ref.

Kapil S, Pomeroy KA, Goyal SM, Trent AM, 1991. Experimental infection with a virulent pneumoenteric isolate of bovine coronavirus. Journal of Veterinary Diagnostic Investigation, 3(1):88-89; 6 ref.

Kapil S, Richardson KL, Maag TR, Goyal SM, 1999. Characterization of bovine coronavirus isolates from eight different states in the USA. Veterinary Microbiology, 67(3):221-230; 22 ref.

Kapil S, Richardson KL, Radi C, Chard-Bergstrom C, 1996. Factors affecting isolation and propagation of bovine coronavirus in human rectal tumor-18 cell line. Journal of Veterinary Diagnostic Investigation, 8(1):96-99; 16 ref.

Kapil S, Trent AM, Goyal SM, 1990. Excretion and persistence of bovine coronavirus in neonatal calves. Archives of Virology, 115(1-2):127-132; 12 ref.

Kapil S, Trent AM, Goyal SM, 1994. Antibody responses in spiral colon, ileum, and jejunum of bovine coronavirus-infected neonatal calves. Comparative Immunology, Microbiology and Infectious Diseases, 17(2):139-149; 13 ref.

Kienzle TE, Abraham S, Hogue BG, Brian DA, 1990. Structure and orientation of expressed bovine coronavirus hemagglutinin-esterase protein. Journal of Virology, 64(4):1834-1838; 40 ref.

Koromyslov GF, Avilov VS, Gogolev MM, Sokolova NL, Mnikova LA, Matyugina NI, 1984. Rotavirus and coronavirus infections in calves. Vestnik Sel'skokhozyaistvennoi Nauki, No.7:129-136; 16 ref.

Krpata V, 1985. Bovine coronavirus-virological and serological screening. Sborník Vedeckych Prací ústredního Státního Veterinárního ústavu v Praze, No.15:30-36.

Krupicka V, 1990. Knowledge gained from virological monitoring of bovine coronavirus infections. Sborník Vedeckych Prací Ustredního Státního Veterinárního ústavu v Praze, No.20(3-7):Czechoslovakia.

Langpap TJ, Bergeland ME, Reed DE, 1979. Coronalviral enteritis of young calves: Virologic and pathologic findings in naturally occurring infections. Am. J. Vet. Res., 40:1476-1478.

Larsson B, Niskanen R, TrÅvén M, Jacobsson SO, Alenius S, Linde N, Rockborn G, 1991. Bovine coronavirus - the cause of infectious diarrhoea (winter dysentery) in dairy herds. Svensk Veterinärtidning, 43(13):547-550; 12 ref.

Läuchli C, Kocherhans R, Wyler R, 1990. Multiple viral infections of the respiratory tract of cattle during the winter of 1986/87. Wiener Tierärztliche Monatsschrift, 77(4):109-110, 112-116; 37 ref.

Laval A, Khelef D, Viso M, Cauchy JC, L'Haridon R, Laporte J, 1986. Excretion of bovine coronavirus and evaluation of serum antibodies in cows and calves in three French herds during several months. Proceedings of the 14th World Congress on Diseases of Cattle, Dublin, 1:348-349; 5 ref.

Lee C, Lee G, Nam S, 1995. Seroepidemiological studies on virus-borne diseases of cattle in the Kwangju and Chonnam areas. Korean J. of Vet. Res., 35(3):615-623.

Li YouMin, Yao XiangYan, Chang GuoQuan, Ye YuanSen, Yang ShengHua, Han HuiMin, Pan YaoQian, Meng QiRui, Xia ZhiPing, Hou ZhenYu, Wang ZuoYou, Liang Ji, Li Min, 1996. Aetiological studies on bovine "sudden death". Chinese Journal of Veterinary Science, 16(4):350-355; 11 ref.

Lu CP, Yao HC, Eichhorn W, 1991. Coronavirus as an agent of neonatal calf diarrhea in a Chinese dairy cattle farm. Journal of Veterinary Medicine. Series B, 38(6):473-476; 8 ref.

Majhdi F, Minocha HC, Kapil S, 1997. Isolation and characterization of a coronavirus from elk calves with diarrhea. Journal of Clinical Microbiology, 35(11):2937-2942; 19 ref.

Mebus CA, Stair EL, Rhodes MB, Twiehaus MJ, 1973. Pathology of neonatal calf diarrhoea induced by a coronavirus-like agent. Vet Pathol. 10:45-64.

Murakami T, Hirano N, Inoue A, Tsuchiya K, Chitose K, Ono K, Yanagihara T, 1986. Prevention of calf diarrhea with an immunoglobulin diet in beef herds. Japanese Journal of Veterinary Science, 48(5):879-885; 19 ref.

Panighi M, Saif L, Schudel A, Zabal O, Fernández F, 1992. Bovine coronavirus: detection of antibodies in cattle in the Argentine Republic. Veterinaria Argentina, 9(87):458, 460-462; 17 ref.

Paton D, Christiansen K, Alenius S, Cranwell M, Pritchard G, Drew T, 1998. Prevalence of antibodies to bovine virus diarrhoea and other viruses in bulk tank milk in England and Wales. Veterinary Record, 142(15):385-391.

Pinto GB, Hawkes P, Zábal O, Ulloa E, Lager IA, Weber EL, Schudel AA, 1993. Viral antibodies in bovine fetuses in Argentina. Research in Veterinary Science, 55(3):385-388; 23 ref.

Putra KSA, Della Porta AJ, 1985. Indonesia. Veterinary viral diseases and their significance in South East Asia and the Western Pacific, 184-191.

Ratafia M, 1988. Genetically engineered vaccines: World business opportunities. Am. Clin. Prod. Rev., 7:18-21.

Saif LJ, 1990. A review of evidence implicating bovine coronavirus in the aetiology of winter dysentery in cows: an enigma resolved ?. Cornell Veterinarian, 80(4):303-311; 32 ref.

Saif LJ, Brock KV, Redman DR, Kohler EM, 1991. Winter dysentery in dairy herds: electron microscopic and serological evidence for an association with coronavirus infection. Veterinary Record, 128(19):447-449; 20 ref.

Schoenthaler SL, Kapil S, 1999. Development and applications of a bovine coronavirus antigen detection enzyme-linked immunosorbent assay. Clinical and Diagnostic Laboratory Immunology, 6(1):130-132; 13 ref.

Schultze B, Herrler G, 1992. Bovine coronavirus uses N-acetyl-9-O-acetylneuraminic acid as a receptor determinant to initiate the infection of cultured cells. Journal of General Virology, 73(4):901-906; 23 ref.

Siddell SG, 1995. The coronaviridae. The coronaviridae., xviii + 418 pp.; Many ref.

Smith DR, Fedorka-Cray PJ, Mohan R, Brock KV, Wittum TE, Morley PS, Hoblet KH, Saif LJ, 1998. Epidemiologic herd-level assessment of causative agents and risk factors for winter dysentery in dairy cattle. American Journal of Veterinary Research, 59(8):994-1001; 39 ref.

Sokolova NL, Mnikova LA, Sattorov IT, 1987. Detecting bovine coronavirus by immunofluorescence. Trudy Vsesoyuznogo Instituta Eksperimental'noi Veterinarii, 64:16-17.

Storz J, Rott R, 1981. Reactivity of antibodies in human serum with antigens of an enteropathogenic bovine coronavirus. Med. Microbiol. Immunol., 169(3):169-78.

Storz J, Stine L, Liem A, Anderson GA, 1996. Coronavirus isolation from nasal swab samples in cattle with signs of respiratory tract disease after shipping. Journal of the American Veterinary Medical Association, 208(9):1452-1455; 31 ref.

Straub O, Trenti F, 1994. Viral respiratory infections of cattle. Proceedings 18th World Butatrics Congress: 26th Congress of the Italian Association of Butatrics, Bologna, Italy, August 29-September 2, 1994, 1:79-94.

Taniguchi S(et al), 1986. Recurrence of bovine coronavirus infection in cows. Journal of the Japan Veterinary Medical Association, 39(5):298-302; 9 ref.

Tegtmeier C, Uttenthal A, Friis NF, Jensen NE, Jensen HE, 1999. Pathological and microbiological studies on pneumonic lungs from Danish calves. Journal of Veterinary Medicine. Series B, 46(10):693-700; 32 ref.

Thurber ET, Bass EP, Beckenhauer WH, 1977. Field trial evaluation of a reo-coronavirus calf diarrhoea vaccine. Cand. J. Comp. Med., 41:131-136.

Torres-Medina A, Schlafer DH, Mebus CA, 1985. Rotaviral and coronaviral diarrhea. Veterinary Clinics of North America, Food Animal Practice, 1(3):471-493; [12 fig.]; 93 ref.

Tråvén M, Björnerot L, Larsson B, 1999. Nationwide survey of antibodies to bovine coronavirus in bulk milk from Swedish dairy herds. Veterinary Record, 144(19):527-529; 13 ref.

Tsunemitsu H, El-Kanawati R, Smith DR, Reed HH, Saif LJ, 1995. Isolation of coronaviruses antigenically indistinguishable from bovine coronavirus from wild ruminants with diarrhea. Journal of Clinical Microbiology, 33(12):3264-3269; 33 ref.

Van Regenmortal MHV, Fauquet CM, Bishop DHL, 1999. Virus Taxonomy: The Classification and Nomenclature of Viruses. The Seventh Report of the International Committee on Taxonomy of Viruses. San Diego, Calif., London: Academic.

Woode GN, Bridger JC, Meyling A, 1978. Significance of bovine coronavirus infection. Vet. Rec., 102:15-6.

Zhang Z, Andrews GA, Chard-Bergstrom C, Minocha HC, Kapil S, 1997. Application of immunohistochemistry and in situ hybridization for detection of bovine coronavirus in paraffin-embedded, formalin-fixed intestines. Journal of Clinical Microbiology, 35(11):2964-2965; 11 ref.

Images

Picture Title Caption Copyright

	Symptoms 	Calf suffering from bovine coronavirus infection. Calf appears weak, dehydrated with sunken eyes, bloody diarrhoea and its hind quarters are soiled with liquid faeces. 	S. Kapil 
	Pathology 	Lesions are confined to the ventral part of the lungs. Haemorragic lesions are evident. On histopathology there are pools of blood in alveoli and pneumonia is observed. 	S. Kapil 
	Histology 	Interstitial pneumonia in a calf injected with pneumoenteric BCV isolate. 	S. Kapil 
	Histology 	Haemorrhages and congestion in lung section of calf experimentally infected with pneumoenteric isolate of BCV. 	S. Kapil 
	Histopathology 	Section of intestine in which the cells are stained with Z3A5 monoclonal antibody. Z3A5 reacts with spike protein of BCV. These cells are lining the lumen of the villi and there are some dead necrotic cells that have bovine coronavirus antigen inside the villi. Cells are present between villi, which could be macrophages that are loaded with viral antigen. 	S. Kapil 
	Histopathology 	Nasal smear with BCV antigen appearing as apple green fluorescence. Uninfected cells appear brick red. 	S. Kapil

Date of report: 03/04/2011

nimal Health and Production Compendium

Selected sections for: bovine coronavirus Identity Taxonomic Tree Disease/s Table Distribution Table Pathogen Characteristics Host Animals References Images

Datasheet Type(s): Pathogen Identity

Preferred Scientific Name bovine coronavirus Van Regenmortal et al., 1999

Other Scientific Names bovine enteric coronavirus bovine respiratory coronavirus Nebraska calf diarrhea virus Mebus et al., 1973

International Common Names

English acronym BCV BoCV

Taxonomic Tree

Domain: Virus Group: "Positive sense ssRNA viruses" Group: "RNA viruses" Order: Nidovirales Family: Coronaviridae Genus: Coronavirus Species: bovine coronavirus

Disease/s Table

bovine coronavirus infection

Distribution Table

Country Distribution Last Reported Origin First Reported Invasive References Notes ASIA Japan CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 Korea, Republic of CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 Turkey CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 AFRICA Egypt CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 NORTH AMERICA USA CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 EUROPE Hungary CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 Spain CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 Sweden CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001 OCEANIA New Zealand CAB Abstracts data mining CAB ABSTRACTS Data Mining 2001

Pathogen Characteristics Bovine coronavirus belongs to antigenic group 2 of the Coronaviridae and has recently been classified under the order Nidovirales (Siddell, 1995). Nidovirales (from nidus meaning nest) has been designated for the classification because all members produce mRNAs with a common 3' end sequence. Coronaviridae has 3 subgroups; BCV, HCV-OC43, mouse hepatitis virus, rat coronavirus, sialodacryoadenitis virus and porcine haemagglutinating encephalomyelitis virus belonging to antigenic subgroup 2. Bovine coronavirus, like other coronaviruses, is an enveloped, pleomorphic, positive, single-stranded RNA virus (Clark, 1993). The genome of BCV is a nonsegmented RNA of approximately 30 kb in size with a positive polarity (Guy and Brian, 1979). It has a 5' leader sequence and a 3' poly A tail. Replication does not occur in the nucleus; rather the virus multiples within the cytoplasm of cells. Viral particles are 90 to 120 nm in diameter. They contain five major structural proteins i.e., the peplomeric spike protein (S or E2; 200 kDa), nucleocapsid protein (N; 52 kDa), haemagglutinin-esterase protein (HE or E3; 65 kDa), and a small matrix or transmembrane glycoprotein (M or E1; 26 kDa) (Kienzle et al., 1990). Coronaviruses possess a characteristic appearance when viewed under the electron microscope (EM). The virus envelope is seen as a distinct centre from which the spike (S) glycoproteins project. These spikes are 20 nm in length. The spike glycoproteins are longer (outer frill) than the haemagglutinin projections (inner frill) on the viral surface. Bovine coronaviruses can be confused with other viruses such as Bredavirus, which belongs to the family Todoviridae and has a sausage-shaped nucleocapsid but is antigenically different from BCV. Also, villus epithelium is shed during diarrhoea causing rolls of non-viral particles. These rolls can appear coronavirus-like leading to misdiagnosis.

Host Animals

Animal name Context Bos taurus (cattle)

Bubalus bubalis (buffalo) Experimental settings Capreolus capreolus Domesticated host, Wild host Cervidae Domesticated host, Wild host Cervus elaphus (red deer) Domesticated host, Wild host Cervus unicolor Domesticated host Kobus ellipsiprymnus Wild host Odocoileus virginianus Wild host Ovis aries (sheep)

Rattus (rats)

Sus scrofa (pigs)

Syncerus caffer Wild host