CORONAVIRIDAE general introduction into family

Brief description about CORONAVIRIDAE family

1. F .CORONAVIRIDAE PRESENTED BY: ANITTA THOMAS L-2021-V-46-M

2. INTRODUCTION Coronaviridae is a family of enveloped, positive-stranded RNA viruses which infect amphibians , birds and mammals.

3. HISTORY The Coronaviridae were recognized as a new virus family in 1968 . Torovirus and Coronavirus were recognized as separate genera within the Coronaviridae family in 1993. The 1st reported case of Coronavirus infection in animals was in late 1920. First identification of Coronavirus in human was in 1965.

4. classification

5. Phylogenetic tree of 50 Coronaviruses

6. The genome of viruses in the family Coronaviridae consists of a single molecule of linear positive-sense, single-stranded RNA - the largest known nonsegmented RNA viral genomes . In infected cells, these viruses all utilize a distinctive “nested set” transcription strategy in which the expression of genes encoding structural viral proteins is mediated via a nested set of 3’ coterminal subgenomic mRNAs. This unique strategy has been recognized by the establishment of the order Nidovirales (from the Latin nidus, nest ). It is believed currently that warm-blooded flying vertebrates are the definitive hosts for the Coronavirus gene pool. Alpha- and Betacoronavirus - in bats, Gamma - and Deltacoronavirus - in birds.

7. Virion Properties They are enveloped , Size and shape Coronaviruses - 80-220 nm in size, pleomorphic although often spherical Toroviruses and Bafiniviruses - 20-140 nm in size and disc, kidney, or rod-shaped. Coronaviruses have distinctive and large (20 nm long) club shaped spikes (peplomers, composed of trimers of the spike protein). The association of the nucleocapsid (N) protein with the genomic RNA forms the helical nucleocapsid that is surrounded by an icosahedral structure composed of the viral membrane (M) protein. Some coronaviruses also have a second fringe of shorter (5 nm long) spikes (composed of the hemagglutinin-esterase (HE) protein ), a particular characteristics of some Betacoronaviruses .

8. Schematic structure of particles of members of the order Nidovirales .

9. Proteins and its functions The 16 non structural proteins( nps ) are mainly required for transcription and replication of genome, among which nsp1 helps in mRNA degradation nsp3 blocks host innate immune response nsp14 act as exonuclease nsp15 serve as endonuclease.

10. The major virion proteins of the member viruses of the subfamilies Coronavirinae and Torovirinae include a nucleocapsid protein ( N , 50-60 kDa , 19 kDa for Toroviruses ) and several envelope proteins: (1) the spike glycoprotein trimer ( S , 180-220 kDa per monomer); (2) a triple-spanning transmembrane protein ( M , 23-35 kDa ); (3) a minor transmembrane protein ( E , 9-12 kDa ), which together with the M protein is essential for Coronavirus virion assembly and budding.

11. The 4 structural proteins helps in viral assembly and occurrence of infections. S protein - The homotrimer of S protein produce spikes on the surface and are cleaved into S1&S2 that act as fusion and attachment protein during viral attachment to the host cell. M protein - It has 3 transmembrane domain associated with viral envelope that gives shape to virion and promote membrane curvature. E protein - It is responsible for viral assembly , release and pathogenesis , it also act a viroporin which influence the electrochemical balance. N protein - It contains 2 domains (homodimer or homooligomer ) , helps in packaging of genome and antagonize interferon type 1 , that is beneficial for viral replication. Some coronaviruses i.e Betacoronavirus encodes some special protein and accessory protein such as HE with haemaglutinating and estaerase activity and 3a/b,4a/b proteins.

12. Toroviruses lack a homolog of the Coronavirus E protein , which may explain the structural differences between the Coronaviruses and Toroviruses . Virus neutralizing antibodies generated during natural infections are directed at the surface glycoproteins of Coronaviruses and Toroviruses - majority being conformational epitopes at the N-terminal portion of the S protein . Cellular immune responses are principally directed toward the S and N proteins .

13. Virus Replication ATTACHMENT AND ENTRY The host spectrum/tropism of individual Coronaviruses appears to be largely determined by the S protein - which mediate receptor binding and virus cell fusion (in plasma membrane / endosomes). Virus replication and transcription takes place within an extensive membranous network of virus-modified endoplasmic reticulum-derived vesicles. Individual Coronaviruses utilize a variety of cellular proteins as receptors. Aminopeptidase N (APN or CD13) serves as a receptor for several Alphacoronaviruses.

14. SARS Coronavirus and human Coronavirus NL63 utilize angiotensin converting enzyme 2 (ACE2). MERS coronavirus utilizes dipeptidyl-peptidase 4 (DPP4 or CD26). Some strains of mouse hepatitis virus utilizes carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM-1). Other Betacoronaviruses utilize sialic acids as a primary receptor. In addition to receptor binding, the activation of virus fusion via the action of host cell-specific proteases that cleave spike is likely to be a powerful means of regulating Coronavirus infection and host- or tissue-tropism.

15. Virus replication and transcription Takes place within an extensive membranous network of virus-modified endoplasmic reticulum-derived vesicles. The strategy of viral replication and transcription of the Coronavirus genome is complex. The viral RNA serves as mRNA for synthesis of the RNA dependent RNA polymerase (RdRp). The two large 5’-most open reading frames , ORF1a and ORF1b ( 20 kb in total size) encoding the subunits of the polymerase are translated, the larger via ribosomal frameshifting -as a single polyprotein (pp1a or pp1ab) that is then cleaved by virus-encoded proteases found within the polyprotein, resulting in the production of mature products - nsp1 to nsp16.

16. These proteins then assemble to form the active replicase transcriptase complex , comprising the RNA polymerase (nsp12) and accessory proteins, including a 3’-5’ exonuclease that imparts some degree of “ proof reading ” function during replication. Such proof reading activity is thought to be important in maintaining the integrity of such large RNA genomes. The viral polymerase is used to synthesize full-length negative-sense (complementary) RNA by copying the genome starting at the 3’ end. The antigenome is then copied back into full-length positive-sense genomic RNA. The generation of full-length genomic RNA is done utilizing the replicase activity of the viral RdRp .

17. The RdRp can also synthesize a nested set of RNAs with different sizes that are generated by a discontinuous synthesis of negative-sense RNAs. This is done using the transcriptase activity of the RdRp . The RdRp synthesizes negative-sense RNA by starting to copy at the 3’ end of the genome, it then recognizes internal regulatory sequences, the transcriptional regulatory sequences (TRSs) found upstream of each ORF, where it pauses and translocates to the 5’ end of the genome, guided by sequence complementarity. The RdRp then extends the nascent negative-sense RNA by copying the leader sequence found at the genome’s 5’ end. These negative sense template RNAs, sharing both 5’ and 3’ ends, are copied into positive-sense subgenomic mRNAs which then allow expression of viral genes downstream of the replicase.

18. The template switching employed during transcription is at the heart of the RNA recombination that is a hallmark of Coronavirus replication. The accumulation of point mutations as a result of polymerase errors (infidelity) during transcription (Genetic drift), genetic recombination occurs at high frequency between the genomes of different but related Coronaviruses during coinfection situations. Recombination between Coronaviruses is a direct result of the discontinuous transcription strategy employed by the viral polymerase, and the presence of transcriptional regulatory sequences in the viral genome. Such recombination is likely to be an important mechanism for the generation of the genetic diversity seen with these viruses in nature, and provides a constant potential source of new viruses with novel phenotypic properties, such as host range, tissue tropism, and virulence.

19. subfamily Torovirinae The transcription and replication apparently are similar to those of coronaviruses, except that there are no common 5’ leader sequences on the mRNAs of viruses in the genus Torovirus . As occurs during replication of Coronaviruses, subgenomic negative-sense RNAs complementary to the nested set of mRNAs are also present in Torovirus -infected cells. The fact that these subgenomic RNAs contain 5’ -and 3’ -terminal sequences that are identical to those of genomic RNA implies that they may function as replicons. Viruses in the genus Bafinivirus use the same transcriptional strategy as the coronaviruses and produce their replicase polyproteins from the virus genome and the three structural proteins from a nested set of 3’ -coterminal subgenomic mRNAs, each having a common 5’ leader sequence identical to that of the virus genome.

20. Assembly and Release Following replication and sub-genomic RNA synthesis, the viral structural proteins, S, E, and M are translated and inserted into the endoplasmic reticulum (ER). These proteins move along the secretory pathway into the endoplasmic reticulum-Golgi intermediate compartment ( ERGIC ) There, viral genomes encapsidated by N protein bud into membranes of the ERGIC containing viral structural proteins, forming mature virions. Virions are transported to the cell surface in vesicles and released by exocytosis. After their release, many of the mature enveloped virions remain adherent to the outside of the cell.

21. Coronavirus replication

22. Subfamily Coronavirinae Genus Alphacoronavirus Feline coronavirus (Feline infectious peritonitis virus) Feline infectious peritonitis (FIP) was first described in the 1960s as a systemic and often fatal disease of cats. The pathogenesis of feline infectious peritonitis is complex and not fully characterized. The sporadic occurrence of feline infectious peritonitis is proposed to be the result of mutations of the enteric Coronavirus during natural infection of cats, resulting in the emergence of a virus with an acquired tropism for macrophages.

23. Two distinct serotypes of the virus have been identified, both being able to cause feline infectious peritonitis. Serotype I - majority. Serotype II - relatively rare. Serotype II feline infectious peritonitis viruses grow well in cell culture and utilize amino-peptidase-n (APN) as a receptor. In contrast, serotype I viruses are very difficult to culture , and appear to use a distinct and currently unidentified receptor. Both virus types can cause the 2 clinical forms of feline infectious peritonitis The “wet” form ( with abdominal effusion ) The “dry” form (without abdominal effusion).

24. Clinical Features and Epidemiology Feline infectious peritonitis is a common progressive, debilitating and lethal disease of domestic and wild members of the family F elidae . Disease typically occurs in young or very old cats , or in the context of immune suppression. The initial clinical signs are vague, and affected cats present with anorexia, chronic fever, malaise , and weight loss. Ocular and/or neurological manifestations occur in some individuals. In the classical wet or effusive form - these signs are accompanied by progressive abdominal distention from the accumulation of a highly viscous fluid in the peritoneal cavity and rapid disease progression, with death typically within weeks to months.

25. The dry or non-effusive form of the disease- little or no peritoneal exudate, is more slowly progressive . The wet and dry forms of feline infectious peritonitis are different manifestations of the same infection, and both forms of the disease are characterized by foci of pyogranulomatous inflammation in several organs. A kitten suckling a seropositive queen - persistent viral infection of the gut with chronic fecal shedding is established. Virus and antibodies coexist in the kitten. The animal may remain healthy, but becomes susceptible to development of feline infectious peritonitis should it become stressed or immunosuppressed.

26. Pathogenesis and Pathology The key initiating pathogenic event is the productive infection of monocytes and macrophages by genetic variants (mutants) of the original enteric Coronavirus. Avirulent strains are also less able to sustain virus replication and spread between macrophages. Mutations within the spike (S) - alter the tropism of the ubiquitous avirulent feline enteric Coronavirus to macrophages, which then allows the virus to spread and ultimately to cause feline infectious peritonitis. The lesions - centered on small blood vessels, and vascular injury and leakage are central to the pathogenesis of the wet form of the disease. Perivascular clusters of virus-infected macrophages are characteristically present in the tissues of cats with both the wet and dry forms of feline infectious peritonitis.

27. Humoral immunity is not protective , and may actually enhance disease progression. Antibody-dependent enhancement of infection of macrophages is apparently mediated by neutralizing antibodies to the S protein , making vaccine development problematic. The gross lesions (one of the two forms) The wet form -presence of variable quantities of thick, viscous, clear yellow peritoneal exudate , and the presence of extensive fibrinous plaque with numerous discrete gray-white nodules in the omentum and on the serosal surface of the liver, spleen, intestines, and kidneys .

28. Microscopically, these nodules are composed of aggregates of macrophages and other inflammatory cells (granulomas or pyogranulomas) that characteristically are centered on blood vessels , sometimes with necrosis of the wall of involved vessels. These lesions can occur in many tissues, but omentum and peritoneal serosa, liver, kidney, lung and pleura, pericardium, meninges, brain, and uvea are common sites.

29. The dry form - lesions and pathogenesis similar, but without the fibrinous polyserositis that characterizes the wet form, and discrete pyogranulomas form nodular masses within the parenchyma of affected organs. It is unknown what determines the form of feline infectious peritonitis that develops in an individual cat Individual virus strains can cause either form in different animals and both forms may be present in a single cat .

30. Diagnosis Effusive form : Detection of viral RNA in a sample of the effusion by RT-PCR Measure the total protein in the effusion: if it is less than 35g/L, FIP is extremely unlikely. Albumin to globulin ratio in the effusion: if it is over 0.8, FIP is not present if it is less than 0.4 , FIP may occur. Non-effusive : History, Clinical signs ,biochemistry: hypergammaglobulinaemia ; raised bilirubin without liver enzymes being raised. Hematology : lymphopenia; non-regenerative-usually mild-anaemia. Serology: the infected cat has a high antibody titre to FCoV but some times infected cats are seronegative.

31. Immunity, Prevention, and Control Feline infectious peritonitis is not controlled easily ; control requires the elimination of the virus from the local environment, Requires a high level of hygiene, strict quarantine, and immunoprophylactic measures. Because kittens acquire the infection from their queens, early weaning programs have also been used to interrupt virus transmission. The only commercially available feline infectious peritonitis vaccine contains a temperature-sensitive mutant virus, based on a serotype II virus. Vaccination of infected, seropositive adult cats is not effective. Treatment : Anti inflammatory drug , immunostimulants and antiviral drugs can be used.

32. Vaccines cats 16 weeks of age or older

33. Canine corona virus Canine coronavirus is an alphacoronavirus usually produces a mild - identified in 1971 . The disease commonly occurs in association with canine parvovirus infection, which causes a more severe and sometimes fatal diarrhea. The virus commonly infects pups and is probably worldwide in distribution. Confirmed by laboratory-based procedures. Such as visualization of virus by electron microscopy or may be isolated in primary canine cell culture. Detection of antibody in the sera of pups is of limited value because it may be of maternal origin. Inactivated vaccine is available for the control of canine coronavirus diarrhea.

34. Vaccination: healthy dogs 6 wks and older

35. TRANSMISSIBLE GASTROENTERITIS VIRUS There are four distinct corona virus disease patterns in swine, referred to as (1) vomiting and wasting disease, (2) porcine epidemic diarrhea, (3) transmissible gastroenteritis, and (4) respiratory disease. TGE is a highly contagious enteric disease of swine that occurs throughout much of the world. It is an acute, rapidly spreading, disease of swine of all ages, characterized by diarrhea and vomiting. High mortality in piglets under two weeks of age is common.

36. Clinical Features and Epidemiology Most severe in very young piglets, and include vomiting, profuse watery yellow diarrhea, rapid weight loss, and dehydration. Seronegative neonates succumb within a few days of infection with highly virulent strains, whereas death is uncommon in pigs infected after 2-3 weeks of age. Infections of adult swine typically are asymptomatic. Spread among farms occurs with the introduction of pigs excreting the virus or by mechanical vectors (fomites) such as contaminated vehicles, clothing, instruments, etc.

37. Profuse watery diarrhea Dehydration

38. Pathogenesis and Pathology Incubation period of 18-72 hours. Virus enters the body by ingestion (fecal-oral transmission). Reasons for the susceptibility of very young piglets: (1) their gastric secretions are less acidic (2) renewal of enterocytes lining the intestinal villi from progenitor cells in the intestinal crypts is less rapid than in older pigs; (3) the neonatal immune system is naive and not fully mature; (4) neonates are especially vulnerable to the electrolyte and fluid derangements that result from the maldigestion and severe malabsorption diarrhea.

39. The virus selectively infects and destroys the mature enterocytes lining the small intestinal villi. Results in profound shortening and blunting of villi , with consequent loss of the mucosal absorptive area . This leads to maldigestion because of the loss of critical digestive enzymes such as lactase and other disaccharidases, normally present in the microvillus brush border of villus enterocytes, that are responsible for digestion of milk. The consequence - acidosis, and severe dehydration. Intestinal crypt epithelial cells remain uninfected, so recovery of the integrity and function of villi is rapid if the animal survives the infection. the proliferation of progenitor enterocytes in the crypts also increases intestinal secretion of fluid and electrolytes, which further exacerbates the diarrhea and metabolic pertubations .

40. Viral infection and destruction of enterocytes lining small intestinal villi, leading to malabsorption diarrhea. (A) Causative virus (arrow). (B ) Small intestine of normal piglet (C) Piglet with transmissible gastroenteritis. (D) Selective viral infection of enterocytes lining the intestinal villi.

41. Diagnosis Mucosal impression smears or cryostat sections of intestine from neonatal piglets with acute disease can be stained by immunofluorescence or immunoperoxidase procedures. Antigen capture enzyme-linked immunosorbent assay (ELISA) - in the feces of infected pigs. Virus isolation can be done in porcine kidney, thyroid, or testicle cells. None of these assays definitively differentiates TGE and porcine respiratory coronavirus infections.

42. Immunity, Prevention, and Control Oral vaccines have not proven highly effective. Maternal IgA antibodies, passed to piglets in colostrum and milk, provide protection against infection. Strict sanitation and management practices. 1 st : 2ml 5-7 wks IM before delivery 2 nd : 2ml 2-3 wks IM before delivery. Pregnant sow: 4ml 20-30 days before birth

43. PORCINE EPIDEMIC DIARRHEA VIRUS Clinically similar to transmissible gastroenteritis, but spreads more slowly . The virus that causes this disease is unrelated to the other porcine corona viruses. The main clinical sign in piglets is watery diarrhea , sometimes preceded by vomiting . In adult swine the infection may remain asymptomatic or may be limited to depression, anorexia, and vomiting. The mortality rate in piglets is usually about 50% but may be as high as 90%. Older pigs recover after about 1 week of illness.

44. DIAGNOSIS A may be confirmed by the isolation of virus in primary porcine cell culture Demonstration of antibodies in convalescent swine. Vaccines are not available.

45. PORCINE RESPIRATORY CORONAVIRUS The respiratory variant of transmissible gastroenteritis virus. The virus is a spike protein (S gene) deletion mutant that has lost its enteric tropism. Instead acquired a respiratory tropism and transmission pattern CLINICAL FEATURES AND EPIDEMIOLOGY Mild fever with variable degrees of dyspnea, polypnea, and anorexia. Spreading long distances by airborne respiratory transmission or directly by contact.

46. Pathogenesis and Pathology The large 5’ region deletion in the spike gene accounts for the reduced virulence and altered tropism of this virus. Spread by respiratory droplets and aerosols and, after infection. Replicates in the tonsils, the mucosal epithelium of the nasal mucosa and airways of the lungs, and in both type I and II pneumocytes in alveoli. Virus-induced inflammation and necrosis in the terminal airways and airspaces manifest as bronchointerstitial pneumonia that can affect 5-60% of the lung, even in subclinically infected pigs. The severity of clinical signs and lesions vary, but infection is subclinical in many infected herds.

47. Diagnosis Detected readily in nasal swabs. Two related viruses are only distinguished by virus-specific RT-PCR assays or highly specific competitive ELISA. The virus also can be isolated and grown in pig kidney or testicle cells. IMMUNITY, PREVENTION, AND CONTROL No vaccines for prevention.

48. PORCINE HEMAGGLUTINATING ENCEPHALOMYELITIS VIRUS In piglets less than 2 weeks of age. Characterized by anorexia, hyperesthesia , muscle tremors, paddling of the legs , vomiting, and depression, often leading to emaciation and death. In contrast to transmissible gastroenteritis, diarrhea is not common . Mortality in young piglets is high; older animals often survive but remain permanently stunted .

49. PATHOGENESIS The virus multiplies first in the nasal mucosa, tonsils, lung, and small intestine and then spreads to the central nervous system via peripheral nerves. In the central nervous system, virus is first detected in the sensory nuclei of the trigeminal and vagus nerves , with subsequent spread to the brain stem, cerebrum, and cerebellum. One characteristic clinical sign, vomiting , is due to virus replication in the ganglion distale vagi ; and wasting , is due to neurologic disturbance of the vomition center. Severe, unremitting vomiting leads to malnutrition

50. Diagnosis, Prevention and Control A clinical is confirmed by the isolation of virus in primary porcine cell culture ; growth of the virus is detected by haemagglutination . No vaccines are available, Good husbandry is essential for the prevention and control of the disease

51. Bovine Coronavirus Enteritis Second to rotaviruses as the major cause of diarrhea in young calves . Corona-viruses were first reported as a cause of diarrhea in calves in the United States in 1973, Recognized worldwide.

52. Pathogenesis The pathogenesis is similar to that of rotavirus diarrhea. Disease is seen most commonly in calves at about 1 week of age , the time when antibody in the dam's milk starts to wane and exposure is maximal. The diarrhea usually lasts for 4 or 5 days. The destruction of the absorptive cells of the intestinal epithelium of the small intestine and, to a lesser extent, the large intestine leads to the rapid loss of water and electrolytes. Glucose and lactose metabolism are affected; hypoglycemia, lactic acidosis, and hypervolemia can lead to acute shock, cardiac failure, and death .

53. DIAGNOSIS Initially, diagnosis was based on the detection of virus by electron microscopy, but subsequently the addition of trypsin to bovine cell culture medium was shown to facilitate the isolation of virus. Bovine cells and human HRT-18 cells are used for primary isolation . Viral growth may be recognized by hemadsorption.

54. Prevention and control Available vaccines are not effective because they do not appear to contain sufficient antigenic mass and they evoke protection at the time of maximum risk. One alternative to vaccinating calves is to immunize the dam, thereby promoting elevated antibody levels in the colostrum. Another alternative is to feed calves colostrum and milk from hyperimmunized cows used as donors.

55. Infectious Bronchitis Virus (IBV) An acute, highly contagious respiratory disease of chickens. All ages infected; particularly a problem in laying flocks. Chicks - growth suppression & predisposition to other diseases. Hens - variable production loss and affects egg quality . Turkeys resistant . Various serotype of the virus are: Massachusetts, Connecticut( Affiity for respiratory tract )T, Gray, Holte ( Nephrotoxic)

56. PATHOGENESISS IB virus initially infects and replicates in upper respiratory tract causing the loss of protective lining the sinuses and trachea. After causing viremia, the virus can be detected in kidneys , reproductive tract, and caecal tonsils .

57. Clinical features This disease has 4 form The incubation period is 18–48 hours. Respiratory form : In chicks 1–4 weeks of age, virulent virus strains produce severe respiratory disease, with gasping, coughing, tracheal rales, sneezing, nasal exudate, wet eyes, respiratory distress, and swollen sinuses. Genital form :Infection of young female chicks may result in permanent hypoplasia of the oviduct that is evident later in life as reduced egg production . Egg-laying chickens usually present with reproductive tract involvement that is manifest as a decline or cessation in egg production including abnormal egg that lack calcified shell , thin shells egg , and shells with stipples, distortions , Nephritic form : Acutely infected birds, the kidneys can be pale and swollen , with urates distending the ureters. Gastrointenstinal form : some birds

58. Other clinical signs - restless and huddled together, difficult in breathing, gasping , coughing, sneezing, tracheal rales, nasal discharge, wet eye and swollen sinus, ruffled feathers, morbidity up to 100%. Facial swelling may also occur occasionally, particularly with concurrent bacterial infection of the sinuses. Decrease of feed intake and conversion, loss of body weight increased water intake, wet droppings, depression, lethargy and poor growth in broilers IBV- infected egg abnormalities

59. Postmortem Lesions: Gross: The most frequent finding is mucosal thickening, with serous or catarrhal exudate in the nasal passages, trachea, bronchi, and airsacs . Very young chicks, the main bronchi may be blocked with caseous yellow casts. Pneumonia and conjunctivitis. In laying birds, ova can be congested and sometimes ruptured, with free yolk in the abdominal cavity. Microscopic : Desquamation of respiratory epithelium, edema , epithelial hyperplasia, mononuclear cell infiltration of the submucosa, and regeneration.

60. Airsacculitis Exudate in trachea

61. DIAGNOSIS History of fast spreading respiratory disease ELISA - uses Mass. antigen but get cross reaction with other serotypes. HI - IBV is treated with neuraminidase enzyme before testing because IBV is not naturally hemagglutinating. VN - rises in titer between paired serum samples (2 wks. apart) Agar-gel precipitation test (AGPT) Direct immunofluorescence staining of tracheal tissue smears can be done. Identification of IBV serotype - PCR, monoclonal antibody test, etc. Detection of virus genome (RT-PCR)

62. For virus isolation , 9-11 day old embryonated eggs are inoculated via the allantoic sac route. Changes in main blood vessels in the chorioallantoic membrane and embryo stunting, curling, clubbing of down suggestive of the presence of a coronavirus. IBV-infected embryo Normal embryo

63. Prevention and control Establish and enforce a biosecurity program. Vaccination - complete prevention of IB is difficult because of variation of field strains and the ability of the virus to change. There is little cross protection between serotypes. LIVE - Monovalent - usually Mass. Bivalent - Mass. & Connecticut  Other attenuated strains such as Holland an dArk . 99 are used as vaccines . KILLED - used in breeders and layer pullets to prevent production losses and produce consistently high antibody titers.

64. The first vaccination is typically given in the hatchery when birds are 1 day old, and booster vaccination is given at 10–18 days. Layers or breeders, attenuated vaccines are used for priming, followed by killed oil-adjuvanted booster vaccines.

65. Turkey comb disease First recognized in turkeys in the United States in 1951 and were associated with various enteric disease syndromes, variously termed “ blue comb disease,” “mud fever,” “transmissible enteritis,” and “coronaviral enteritis.” The onset is characterized by loss of appetite, watery diarrhea, dehydration, hypothermia, weight loss, and depression. The duodenum and jejunum are pale and flaccid, and the ceca filled with frothy content cloacal bursa is atrophic. Only palliative treatment is possible .