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Respiratory syncytial virus-associated bronchopneumonia in a young chimpanzee
J. Comp, Path, 1994 VoI. 110, 207-212
SHORT PAPER
Respiratory Syncytial Virus-Associated Bronchopneumonia in a Young Chimpanzee C. J. Clarke, N. J. Watt, A. Meredith*, N. Mclntyre and S. M. Burns~ Departments of Veterinary Pathology and * Veterinary Clinical Studies, University of Edinburgh, Veterinary Field Station, Easter Bush, Roslin, Midlothian, EH25 9RG and ~Regional Virus Laboratory, City Hospital, Greenbank Drive, Edinburgh EHIO 5SB, UK
Summary A fatal bronchopneumonia in a captive, 14-month-old female chimpanzee (Pan troglodytes) is reported. Clinical, necropsy and histopathological findings, together with immunofluorescence and virus isolation studies inaplicated respiratory syncytial virus as the causative agent. The probable pathogenesis is discussed.
Introduction Respiratory syncytial virus (RSV), a pneumovirus of the family Paramyxoviridae, causes respiratory disease in man, other primates and cattle. Various strains have been identified and all are related antigenically (Wilson et al., 1984). T h e prototype R S V (Chimpanzee Coryza Agent) was originally isolated from a chimpanzee with respiratory disease and antigenically similar h u m a n isolates were described subsequently (Morris et al., 1956; Beem et al., 1960). In h u m a n infants R S V is a common cause of upper respiratory tract infection ( U R T I ) and bronchiolitis that may progress to severe bronchitis, pneumonia and death. A milder form of U R T I is seen in older children and adults (Wilson et al., 1984). In some non-human primates a similar disease pattern has been reported, infection causing U R T I in young animals (Belshe et al., 1977; Richardson et al., 1978; Prince et al., 1979). Very few cases have been described in which such relatively minor infections in non-human primates have progressed to cause significant lower respiratory tract lesions and death attributable to RSV. This report describes such a case in a young chimpanzee and confirms the presence of RSV in the pulmonary lesions.
Case Report and Necropsy A 14-month-old female, captive-bred chimpanzee was one of a colony of 11 chimpanzees in the Royal Zoological Society of Scotland's collection at Edinburgh. Following an outbreak of U R T I in some other members of the 0021-9975/94/020207 + 06 $08.00/0
© 1994 Academic Press Limked
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C.J. Clarke et al.
Fig. 1. Section of chimpanzee lung showing alveolar and interstitial pncumonitis and bronchitis. The inflammatory cell infiltrate comprises neutrophil polymorphs, macrophages, lymphocytes and plasma cells. HE. x 10.
colony the animal developed a cough (February 14th) and then a mucopurulent nasal discharge and dyspnoea. Clinical examination revealed only upper respiratory tract inflammation, and oxytetracycline was administered. The chimpanzee remained bright and the clinical signs improved. Despite this the animal died suddenly oil 17 February. At necropsy the carcase (5' 17 kg) was in good bodily condition. Examination showed crusty deposits around the nares, a reddened nasopharyngeal mucosa and prominent tonsils and regional lymph nodes. The trachea and bronchial airways contained a serous and mucoid white froth. Both lungs were diflhsely oedematous and heavy and affected by large patchy lobular areas of red-grey consolidation involving most of the lung surface and tissues. Peripheral lobe areas showed some mild emphysematous change and there were a few fibrinous adhesions between the dorsal lung lobes and adjacent thoracic pleurae. Bronchial lymph nodes were moderately prominent and hyperaemic. Selected tissues were taken for histological and microbiological investigation. M e t h o d s and R e s u l t s
Formalin-fixed tissue blocks were processed and sectioned routinely and stained with haematoxylin and eosin (HE) and phloxine tartrazine (PT). Histopathological examination of lung sections showed extensive bronchopneumonic changes. A marked interstitial and alveolar pneumonitis was evident with approximately equal numbers of mononuclear inflammatory cells (macrophages, lymphocytes and plasma cells) and neutrophil polymorphs, infiltrating diffusely into interalveolar tissues and occupying alveolar spaces (Fig. 1). Pulmonary congestion and oedema of alveolar tissues were
Respiratory Syncytial Virus in a Chimpanzee
209
Fig. 2. Section of lung showing bronchial epithelium with degenerative changes and infiltration by inflammatory cells. The lumen (L) contains many inflammatory cells, mucus and debris. HE. x 20. Fig. 3. Section of lung showing multinucleate syncytial cell with intracytoplasmic inclusion body (arrow) and hyaline membrane formation (arrowhead). HE. x 40. m a r k e d and in some areas fluid and cellular accurnulations had progressed to cause collapse. T e r m i n a l bronchitis and bronchiolitis with peribronchiolar inflammation were evident in the lower airways, with neutrophil polymorphs and rnononuclear i n f l a m m a t o r y c e l l s infiltrating the mucosal layers and present in airway lumina (Fig. 2). A i r w a y epithelium was variously affected by vacuolar degeneration and necrosis,
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and in other areas by cellular swelling and proliferation and epithelial thickening. Multinucleate syncytial cells with eosinophilic cytoplasmic inclusion bodies (also PT-positive) were seen in some places. Degeneration, necrosis, hyaline membranes and multinucleate syncytia with inclusion bodies (Fig. 3) were seen in alveolar epithelium adjacent to affected airways. Cryostat sections of frozen lung tissues were mounted, air-dried, acetone-fixed and stained by a direct immunofluorescence technique with a monoclonal antibody to RSV conjugated with fluorescein isocyanate (Imagen RSV, Dako Diagnostics Ltd, Cambridgeshire, UK). Impression smears made directly from freshly thawed blocks of frozen tissues were stained by a similar direct immunoftuorescence reaction. Sections and smears, viewed with an Epifluorescence microscope with a FITC filter system, showed numerous fluorescent foci corresponding to epithelial cell cytoplasmic areas. Lung sections from a gorilla (without respiratory disease) were clearly negative when processed in a similar way. Virus isolation was attempted from thawed blocks of frozen lung tissues, homogenized and inoculated into monolayer cultures (primary baboon kidney, human epithelial cells and human fibroblasts) which were maintained at 37° or 33°C as appropriate for 21 days. These procedures failed to demonstrate any viable RSV at any stage of culture. Routine bacteriological examination of lung was unrewarding except for the isolation of a small number of coliform-type bacteria. Discussion
The pathology of human RSV infection has been well documented and most infants who succumb to lower respiratory tract disease show signs of either acute bronchiolitis or interstitial pneumonitis (Aherne et al., 1970; Gardner et al., 1970). The chimpanzee pulmonary lesions reflected both elements, showing substantial inflammation and destruction of airway epithelium and a marked interstitial and alveolar pneumonitis. The congestion and oedema, epithelial hyperplasia, fibrinous exudate, hyaline membranes and other changes indicated the severity of the disease and were suggestive of the adult or acute respiratory distress syndrome (ARDS) seen with diffuse pulmonary viral infections in man and cattle (Breeze et al., 1976; Cotran et al., 1989). Multinucleate syncytial cell formation and inclusion bodies also indicated viral infection and immunofluorescenee confirmed the involvement of RSV. The widespread distribution of viral antigen throughout the lung was more consistent with the human pneumonic form than the bronchiolitic form (Gardner et al., 1970). The failure to isolate virus from the chimpanzee may have been a reflection of viral lability in frozen and thawed tissue (Beem et al., 1960) or of the one day delay between death and necropsy. The high proportion of neutrophil polymorphs in the lung was consistent with a severe acute viral pneumonia with epithelial necrosis, as seen in A R D S (Cotran et al., 1989), which might explain the rapid demise of the chimpanzee. Secondary bacterial infection may follow a primary viral infection (Jones et al., 1984). Significant bacterial pathogens were not isolated, but antibiotic treatment m a y have influenced this result. Respiratory disease in non-human primates m a y be caused by m a n y pathogens including a number of viruses (Dick and Dick, 1974; Fowler, 1986). Clinical signs of U R T I due to RSV infection have been recognized in young chimpanzees (Morris el al., 1956; Belshe et al., 1977), cebus monkeys (Richardson et al., 1978) and owl monkeys (Prince et al., 1979), but detailed reports of
Respiratory Syncytlal Virus in aChimpanzee
211
RSV-induced pneumonia are scarce. Soave and Emmons (1979) described a "natural" pneumonia-associated death in a 7,month-old chimpanzee whose serological titres for adenovirus were high, bu t for RSV low. Richardson et al. (1978) also reported that experimental RSVi~feetion of young cebus monkeys led to interstitial pneumonia and the formation of multinucleate giant cells and cytoplasmic inclusion bodies. RSV infection is common throughout the human population in winter (Wilson et al., 1984) and Scottish Virus LaboratOries reported (Anon, 1993) a sizeable outbreak of RSV illness just before the events described in this communication. The antigenic similarity of RSV isolates from man and other primates suggests that cross-species transmission is possible and the similar pulmonary lesions seen in man and the chimpanzee described here would support this. Three adults and another infant in the chimpanzee colony also developed U R T I signs around the same time as the young female and all made uneventful recoveries with antibiotic treatment. No addition to the colony was made in the months preceding the outbreak, and initial infection from a human source therefore appears likely. In the case described RSV infection in a young animal appeared to progress from an U R T I to severe bronchopneumonic lesions, ARDS, and sudden death. The possibility of secondary bacterial infection cannot be ruled out, but histological lesions and the demonstration of RSV antigen implicate RSV as the cause. Acknowledgments We thank Dr O. H. K. Lawson and Ms L. Hume for performing the bacteriological examination. References Aherne, W., Bird, T., Court, S. D. M., Gardner, P. S. and McQuillin, J. (1970). Pathological changes in virus infections of the lower respiratory tract in children. Journal of Clinical Pathology, 23, 7-18. Anon (1993). Communicable Diseases and Environmental Health in Scotland Weekly Report, 27, 93/O6, 2. Beem, M., Wright, F. H., Hamre, D., Egerer, R. and Oeheme, M. (1960). Association of the chimpanzee coryza agent with acute respiratory disease in children. New England Journal of Medicine, 263, 523-530. Belshe R. B., Richardson, L. S., London, W. T., Sly, D. L., Lorfield, J. H., Prevar, D. A. and Chanock, R. M. (1977). Experimental respiratory syncytial virus infection of four species of primates. Journal of Medical Virology, 1, 157-162. Breeze, R. G., Pirie, H. M., Selman, I. E. and Wiseman, A. (1976). Atypical interstitial pneumonia and fog fever. Veterinary Record, 98, 38-139. Cotran, R. S., Kumar, V. and Robbins, S. C. (1989). In: Pathologic Basis of Disease, 4th Edit., W. B. Saunders, London. Dick, E. C. and Dick, C. R. (1974). Natural and experimental infections of nonhuman primates with respiratory viruses. Laboralory Anima! Science, 24, 177-I81. Fowler, M. E. (Ed.) (1986). In: Zoo and Wild Animal medicine, 2nd Edit., W. B. Saunders, London. Gardner, P. S., McQuillin,J. and Court, S. D. M. (1970). Speculation on pathogenesis in death from respiratory syncytial virus infection. British Medical Journal, 1, 327-330.
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Jones, E. E., Alford, P. L., Reingold, A. L., Russell, H., Keeling, M. E. and Broome, C. V. (1984). Predisposition to invasive pneumococcal illness following parainfluenza type 3 virus infection in chimpanzees. Journal of the American VeterinaryAssociation, 185, 1351-1353. Morris, J. A., Blount, R. E. and Savage, R::E. (1956). Recovery of cytopathogenic agent from chimpanzees with coryza. Proceedings of the Societyfor Experimental Biology and Medicine, 92, 544-549. Prince, G. A., Suffin, S. C., Prevar, D. A., Camargo, E., Sly, D. L., London, W. T. and Chanock, R. M. (1979). Respiratory.s,)/ncytial virus infection in owl monkeys: v!ral shedding, immunological response, and associated illness caused by wild-type virus and two temperature-sensitive mutants. Infection and Immunity, 26, 1009-1013. Richardson, L. S., Belshe, R. B., Sly, D. L., London, W. T., Prevar, D. A., Camargo, E. and Chanock, R. M., (1978). Experimental respiratory syncytial virus pneumonia in cebus monkeys. Journal of Medical Virology, 2, 45-59. Soave, O. A. and Emmons, R. W. (1979)2 Suspected adenovirus or respiratory syncytial virus illness in a cotony of chimpanzees. LaboratoryPrimate Newsletter, 18, 3-9. Wilson, G. S., Miles, A. A. and Parker, M. T. (Eds) (1984). In: Topley and Wilson's Principles of Bacteriology, Virologyand Immz~ity, Vol. 4, Virology, 7th Edit., Edward Arnold, London, pp. 390-391.
I Received,June 16~th, 1993 Accepted, October26th, 1993J
SHORT PAPER
Respiratory Syncytial Virus-Associated Bronchopneumonia in a Young Chimpanzee C. J. Clarke, N. J. Watt, A. Meredith*, N. Mclntyre and S. M. Burns~ Departments of Veterinary Pathology and * Veterinary Clinical Studies, University of Edinburgh, Veterinary Field Station, Easter Bush, Roslin, Midlothian, EH25 9RG and ~Regional Virus Laboratory, City Hospital, Greenbank Drive, Edinburgh EHIO 5SB, UK
Summary A fatal bronchopneumonia in a captive, 14-month-old female chimpanzee (Pan troglodytes) is reported. Clinical, necropsy and histopathological findings, together with immunofluorescence and virus isolation studies inaplicated respiratory syncytial virus as the causative agent. The probable pathogenesis is discussed.
Introduction Respiratory syncytial virus (RSV), a pneumovirus of the family Paramyxoviridae, causes respiratory disease in man, other primates and cattle. Various strains have been identified and all are related antigenically (Wilson et al., 1984). T h e prototype R S V (Chimpanzee Coryza Agent) was originally isolated from a chimpanzee with respiratory disease and antigenically similar h u m a n isolates were described subsequently (Morris et al., 1956; Beem et al., 1960). In h u m a n infants R S V is a common cause of upper respiratory tract infection ( U R T I ) and bronchiolitis that may progress to severe bronchitis, pneumonia and death. A milder form of U R T I is seen in older children and adults (Wilson et al., 1984). In some non-human primates a similar disease pattern has been reported, infection causing U R T I in young animals (Belshe et al., 1977; Richardson et al., 1978; Prince et al., 1979). Very few cases have been described in which such relatively minor infections in non-human primates have progressed to cause significant lower respiratory tract lesions and death attributable to RSV. This report describes such a case in a young chimpanzee and confirms the presence of RSV in the pulmonary lesions.
Case Report and Necropsy A 14-month-old female, captive-bred chimpanzee was one of a colony of 11 chimpanzees in the Royal Zoological Society of Scotland's collection at Edinburgh. Following an outbreak of U R T I in some other members of the 0021-9975/94/020207 + 06 $08.00/0
© 1994 Academic Press Limked
208
C.J. Clarke et al.
Fig. 1. Section of chimpanzee lung showing alveolar and interstitial pncumonitis and bronchitis. The inflammatory cell infiltrate comprises neutrophil polymorphs, macrophages, lymphocytes and plasma cells. HE. x 10.
colony the animal developed a cough (February 14th) and then a mucopurulent nasal discharge and dyspnoea. Clinical examination revealed only upper respiratory tract inflammation, and oxytetracycline was administered. The chimpanzee remained bright and the clinical signs improved. Despite this the animal died suddenly oil 17 February. At necropsy the carcase (5' 17 kg) was in good bodily condition. Examination showed crusty deposits around the nares, a reddened nasopharyngeal mucosa and prominent tonsils and regional lymph nodes. The trachea and bronchial airways contained a serous and mucoid white froth. Both lungs were diflhsely oedematous and heavy and affected by large patchy lobular areas of red-grey consolidation involving most of the lung surface and tissues. Peripheral lobe areas showed some mild emphysematous change and there were a few fibrinous adhesions between the dorsal lung lobes and adjacent thoracic pleurae. Bronchial lymph nodes were moderately prominent and hyperaemic. Selected tissues were taken for histological and microbiological investigation. M e t h o d s and R e s u l t s
Formalin-fixed tissue blocks were processed and sectioned routinely and stained with haematoxylin and eosin (HE) and phloxine tartrazine (PT). Histopathological examination of lung sections showed extensive bronchopneumonic changes. A marked interstitial and alveolar pneumonitis was evident with approximately equal numbers of mononuclear inflammatory cells (macrophages, lymphocytes and plasma cells) and neutrophil polymorphs, infiltrating diffusely into interalveolar tissues and occupying alveolar spaces (Fig. 1). Pulmonary congestion and oedema of alveolar tissues were
Respiratory Syncytial Virus in a Chimpanzee
209
Fig. 2. Section of lung showing bronchial epithelium with degenerative changes and infiltration by inflammatory cells. The lumen (L) contains many inflammatory cells, mucus and debris. HE. x 20. Fig. 3. Section of lung showing multinucleate syncytial cell with intracytoplasmic inclusion body (arrow) and hyaline membrane formation (arrowhead). HE. x 40. m a r k e d and in some areas fluid and cellular accurnulations had progressed to cause collapse. T e r m i n a l bronchitis and bronchiolitis with peribronchiolar inflammation were evident in the lower airways, with neutrophil polymorphs and rnononuclear i n f l a m m a t o r y c e l l s infiltrating the mucosal layers and present in airway lumina (Fig. 2). A i r w a y epithelium was variously affected by vacuolar degeneration and necrosis,
210
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e t al.
and in other areas by cellular swelling and proliferation and epithelial thickening. Multinucleate syncytial cells with eosinophilic cytoplasmic inclusion bodies (also PT-positive) were seen in some places. Degeneration, necrosis, hyaline membranes and multinucleate syncytia with inclusion bodies (Fig. 3) were seen in alveolar epithelium adjacent to affected airways. Cryostat sections of frozen lung tissues were mounted, air-dried, acetone-fixed and stained by a direct immunofluorescence technique with a monoclonal antibody to RSV conjugated with fluorescein isocyanate (Imagen RSV, Dako Diagnostics Ltd, Cambridgeshire, UK). Impression smears made directly from freshly thawed blocks of frozen tissues were stained by a similar direct immunoftuorescence reaction. Sections and smears, viewed with an Epifluorescence microscope with a FITC filter system, showed numerous fluorescent foci corresponding to epithelial cell cytoplasmic areas. Lung sections from a gorilla (without respiratory disease) were clearly negative when processed in a similar way. Virus isolation was attempted from thawed blocks of frozen lung tissues, homogenized and inoculated into monolayer cultures (primary baboon kidney, human epithelial cells and human fibroblasts) which were maintained at 37° or 33°C as appropriate for 21 days. These procedures failed to demonstrate any viable RSV at any stage of culture. Routine bacteriological examination of lung was unrewarding except for the isolation of a small number of coliform-type bacteria. Discussion
The pathology of human RSV infection has been well documented and most infants who succumb to lower respiratory tract disease show signs of either acute bronchiolitis or interstitial pneumonitis (Aherne et al., 1970; Gardner et al., 1970). The chimpanzee pulmonary lesions reflected both elements, showing substantial inflammation and destruction of airway epithelium and a marked interstitial and alveolar pneumonitis. The congestion and oedema, epithelial hyperplasia, fibrinous exudate, hyaline membranes and other changes indicated the severity of the disease and were suggestive of the adult or acute respiratory distress syndrome (ARDS) seen with diffuse pulmonary viral infections in man and cattle (Breeze et al., 1976; Cotran et al., 1989). Multinucleate syncytial cell formation and inclusion bodies also indicated viral infection and immunofluorescenee confirmed the involvement of RSV. The widespread distribution of viral antigen throughout the lung was more consistent with the human pneumonic form than the bronchiolitic form (Gardner et al., 1970). The failure to isolate virus from the chimpanzee may have been a reflection of viral lability in frozen and thawed tissue (Beem et al., 1960) or of the one day delay between death and necropsy. The high proportion of neutrophil polymorphs in the lung was consistent with a severe acute viral pneumonia with epithelial necrosis, as seen in A R D S (Cotran et al., 1989), which might explain the rapid demise of the chimpanzee. Secondary bacterial infection may follow a primary viral infection (Jones et al., 1984). Significant bacterial pathogens were not isolated, but antibiotic treatment m a y have influenced this result. Respiratory disease in non-human primates m a y be caused by m a n y pathogens including a number of viruses (Dick and Dick, 1974; Fowler, 1986). Clinical signs of U R T I due to RSV infection have been recognized in young chimpanzees (Morris el al., 1956; Belshe et al., 1977), cebus monkeys (Richardson et al., 1978) and owl monkeys (Prince et al., 1979), but detailed reports of
Respiratory Syncytlal Virus in aChimpanzee
211
RSV-induced pneumonia are scarce. Soave and Emmons (1979) described a "natural" pneumonia-associated death in a 7,month-old chimpanzee whose serological titres for adenovirus were high, bu t for RSV low. Richardson et al. (1978) also reported that experimental RSVi~feetion of young cebus monkeys led to interstitial pneumonia and the formation of multinucleate giant cells and cytoplasmic inclusion bodies. RSV infection is common throughout the human population in winter (Wilson et al., 1984) and Scottish Virus LaboratOries reported (Anon, 1993) a sizeable outbreak of RSV illness just before the events described in this communication. The antigenic similarity of RSV isolates from man and other primates suggests that cross-species transmission is possible and the similar pulmonary lesions seen in man and the chimpanzee described here would support this. Three adults and another infant in the chimpanzee colony also developed U R T I signs around the same time as the young female and all made uneventful recoveries with antibiotic treatment. No addition to the colony was made in the months preceding the outbreak, and initial infection from a human source therefore appears likely. In the case described RSV infection in a young animal appeared to progress from an U R T I to severe bronchopneumonic lesions, ARDS, and sudden death. The possibility of secondary bacterial infection cannot be ruled out, but histological lesions and the demonstration of RSV antigen implicate RSV as the cause. Acknowledgments We thank Dr O. H. K. Lawson and Ms L. Hume for performing the bacteriological examination. References Aherne, W., Bird, T., Court, S. D. M., Gardner, P. S. and McQuillin, J. (1970). Pathological changes in virus infections of the lower respiratory tract in children. Journal of Clinical Pathology, 23, 7-18. Anon (1993). Communicable Diseases and Environmental Health in Scotland Weekly Report, 27, 93/O6, 2. Beem, M., Wright, F. H., Hamre, D., Egerer, R. and Oeheme, M. (1960). Association of the chimpanzee coryza agent with acute respiratory disease in children. New England Journal of Medicine, 263, 523-530. Belshe R. B., Richardson, L. S., London, W. T., Sly, D. L., Lorfield, J. H., Prevar, D. A. and Chanock, R. M. (1977). Experimental respiratory syncytial virus infection of four species of primates. Journal of Medical Virology, 1, 157-162. Breeze, R. G., Pirie, H. M., Selman, I. E. and Wiseman, A. (1976). Atypical interstitial pneumonia and fog fever. Veterinary Record, 98, 38-139. Cotran, R. S., Kumar, V. and Robbins, S. C. (1989). In: Pathologic Basis of Disease, 4th Edit., W. B. Saunders, London. Dick, E. C. and Dick, C. R. (1974). Natural and experimental infections of nonhuman primates with respiratory viruses. Laboralory Anima! Science, 24, 177-I81. Fowler, M. E. (Ed.) (1986). In: Zoo and Wild Animal medicine, 2nd Edit., W. B. Saunders, London. Gardner, P. S., McQuillin,J. and Court, S. D. M. (1970). Speculation on pathogenesis in death from respiratory syncytial virus infection. British Medical Journal, 1, 327-330.
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e t al.
Jones, E. E., Alford, P. L., Reingold, A. L., Russell, H., Keeling, M. E. and Broome, C. V. (1984). Predisposition to invasive pneumococcal illness following parainfluenza type 3 virus infection in chimpanzees. Journal of the American VeterinaryAssociation, 185, 1351-1353. Morris, J. A., Blount, R. E. and Savage, R::E. (1956). Recovery of cytopathogenic agent from chimpanzees with coryza. Proceedings of the Societyfor Experimental Biology and Medicine, 92, 544-549. Prince, G. A., Suffin, S. C., Prevar, D. A., Camargo, E., Sly, D. L., London, W. T. and Chanock, R. M. (1979). Respiratory.s,)/ncytial virus infection in owl monkeys: v!ral shedding, immunological response, and associated illness caused by wild-type virus and two temperature-sensitive mutants. Infection and Immunity, 26, 1009-1013. Richardson, L. S., Belshe, R. B., Sly, D. L., London, W. T., Prevar, D. A., Camargo, E. and Chanock, R. M., (1978). Experimental respiratory syncytial virus pneumonia in cebus monkeys. Journal of Medical Virology, 2, 45-59. Soave, O. A. and Emmons, R. W. (1979)2 Suspected adenovirus or respiratory syncytial virus illness in a cotony of chimpanzees. LaboratoryPrimate Newsletter, 18, 3-9. Wilson, G. S., Miles, A. A. and Parker, M. T. (Eds) (1984). In: Topley and Wilson's Principles of Bacteriology, Virologyand Immz~ity, Vol. 4, Virology, 7th Edit., Edward Arnold, London, pp. 390-391.
I Received,June 16~th, 1993 Accepted, October26th, 1993J