title: Sendai virus, a murine parainfluenza virus type 1, replicates to a level similar to human PIV1 in the upper and lower respiratory tract of African green monkeys and chimpanzees.
abstract: Human parainfluenza virus type 1 (HPIV1), a major cause of croup in infants and young children, accounts for 6% of hospitalizations for pediatric respiratory tract disease. The antigenically related Sendai virus, referred to here as murine PIV1 (MPIV1), is being considered for use as a live-attenuated vaccine to protect against HPIV1 (J. L. Hurwitz, K. F. Soike, M. Y., Sangster, A. Portner, R. E. Sealy, D. H. Dawson, and C. Coleclough, 1997, Vaccine 15(5), 533-540) and also as a recombinant vaccine vector expressing antigens to protect against viral disease in humans. However, in the 1950s MPIV1 was reported to have been isolated from humans, suggesting that zoonotic transmission might have occurred. It is therefore important to examine the ability of MPIV1 to replicate in nonhuman primates, i.e., surrogate hosts for humans. In the present study the level of replication of MPIV1 and HPIV1 was compared in African green monkeys and chimpanzees. Surprisingly, MPIV1 replicated as efficiently as HPIV1 in the upper and lower respiratory tract of African green monkeys at doses of 10(4) and 10(6) and replicated only slightly less efficiently at both sites in chimpanzees. African green monkeys immunized with MPIV1 were highly resistant to subsequent challenge with HPIV1 even though MPIV1 did not induce a detectable HPIV1-neutralizing antibody response. The high level of replication of MPIV1 observed in the upper and lower respiratory tract of these primates suggests that MPIV1 likely would require significant attenuation before it could be given to humans as a vaccine against HPIV1 or as a vaccine vector. Its ability to efficiently replicate in nonhuman primates suggests that MPIV1 lacks a significant host range restriction in primates and could theoretically cause zoonotic disease in humans.
authors.affiliation: Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mskiadopoulos@niaid.nih.gov
authors.forename: Mario H
authors.initials: MH
authors.lastname: Skiadopoulos
authors.forename: Sonja R
authors.initials: SR
authors.lastname: Surman
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Riggs
authors.forename: William R
authors.initials: WR
authors.lastname: Elkins
authors.forename: Marisa
authors.initials: M
authors.lastname: St  Claire
authors.forename: Machiko
authors.initials: M
authors.lastname: Nishio
authors.forename: Dominique
authors.initials: D
authors.lastname: Garcin
authors.forename: Daniel
authors.initials: D
authors.lastname: Kolakofsky
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002522:Chlorocebus aethiops / Q000821:virology*; D004195:Disease Models, Animal; D009500:Neutralization Tests; D002679:Pan troglodytes / Q000821:virology*; D010222:Parainfluenza Virus 1, Human / Q000276:immunology / Q000502:physiology*; D012137:Respiratory System / Q000821:virology*; D010253:Respirovirus Infections / Q000276:immunology / Q000517:prevention & control; D029082:Sendai virus / Q000276:immunology / Q000502:physiology*; D013045:Species Specificity; D014613:Vaccines, Attenuated; D014765:Viral Vaccines / Q000008:administration & dosage; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines