A recombinant human parainfluenza virus type 3 (PIV3) in which the nucleocapsid N protein has been replaced by that of bovine PIV3 is at attenuated in primates

被引:33
作者
Bailly, JE [1 ]
McAuliffe, JM [1 ]
Durbin, AP [1 ]
Elkins, WR [1 ]
Collins, PL [1 ]
Murphy, BR [1 ]
机构
[1] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1128/JVI.74.7.3188-3195.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The shipping fever (SF) and Kansas (Ka) strains of bovine parainfluenza virus type 3 (BPIV3) are restricted in their replication in rhesus monkeys 100- to 1,000-fold compared to human parainfluenza virus type 3 (HPIV3), and the Ba strain also was shown to be attenuated in humans. To initiate an investigation of the genetic basis of the attenuation of BPIV3 in primates, we produced viable chimeric HPIV3 recombinants containing the nucleoprotein (N) open reading frame (ORF) from either BPIV3 Ka or SF in place of the HPIV3 N ORF. These chimeric recombinants mere designated cKa-N and cSF-N, respectively. Remarkably, cKa-N and cSF-N grew to titers comparable to those of their HPIV3 and BPIV3 parents in LLC-MK2 monkey kidney and Madin-Darby bovine kidney cells, Thus, the heterologous nature of the N protein did not impede replication in vitro, However, cKa-N and cSF-N were each restricted in replication in rhesus monkeys to a similar extent as Iia and SF, respectively. This identified the BPIV3 N protein as a determinant of;the host range restriction of BPIV3 in primates. These chimeras thus combine the antigenic determinants of BPIV3 with the host range restriction and attenuation phenotype of BPIV3, Despite their restricted replication in rhesus monkeys, the chimeric viruses induced a level of resistance to HPIV3 challenge in these animals which was indistinguishable from that conferred by immunization with HPIV3. The infectivity, attenuation, and immunogenicity of these BPIV3/HPIV3 chimeras suggest that the modified Jennerian approach described in the present report represents a novel method to design vaccines to protect against HPIV3-induced disease in humans.
引用
收藏
页码:3188 / 3195
页数:8
相关论文
共 31 条
[21]   ANTIGENIC VARIATION OF HUMAN AND BOVINE PARAINFLUENZA VIRUS TYPE-3 STRAINS [J].
KLIPPMARK, E ;
RYDBECK, R ;
SHIBUTA, H ;
NORRBY, E .
JOURNAL OF GENERAL VIROLOGY, 1990, 71 :1577-1580
[22]  
KUNKEL TA, 1987, METHOD ENZYMOL, V154, P367
[23]   Pediatric hospitalizations for croup (laryngotracheobronchitis): Biennial increases associated with human parainfluenza virus 1 epidemics [J].
Marx, A ;
Torok, TJ ;
Holman, RC ;
Clarke, MJ ;
Anderson, LJ .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (06) :1423-1427
[24]   DOSE-RESPONSE OF INFLUENZA-A WASHINGTON 897/80 (H3N2) AVIAN-HUMAN REASSORTANT VIRUS IN ADULT VOLUNTEERS [J].
MURPHY, BR ;
CLEMENTS, ML ;
TIERNEY, EL ;
BLACK, RE ;
STIENBERG, J ;
CHANOCK, RM .
JOURNAL OF INFECTIOUS DISEASES, 1985, 152 (01) :225-229
[25]   THE P-GENE OF BOVINE PARAINFLUENZA VIRUS-3 EXPRESSES ALL 3 READING FRAMES FROM A SINGLE MESSENGER-RNA EDITING SITE [J].
PELET, T ;
CURRAN, J ;
KOLAKOFSKY, D .
EMBO JOURNAL, 1991, 10 (02) :443-448
[26]   Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela [J].
PerezSchael, I ;
Guntinas, MJ ;
Perez, M ;
Pagone, V ;
Rojas, AM ;
Gonzalez, R ;
Cunto, W ;
Hoshino, Y ;
Kapikian, AZ .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (17) :1181-1187
[27]   Identification of mutations contributing to the temperature-sensitive, cold-adapted, and attenuation phenotypes of the live-attenuated cold-passage 45 (cp45) human parainfluenza virus 3 candidate vaccine [J].
Skiadopoulos, MH ;
Surman, S ;
Tatem, JM ;
Paschalis, M ;
Wu, SL ;
Udem, SA ;
Durbin, AP ;
Collins, PL ;
Murphy, BR .
JOURNAL OF VIROLOGY, 1999, 73 (02) :1374-1381
[28]   EVALUATION OF LIVE AVIAN-HUMAN REASSORTANT INFLUENZA A H3N2 AND H1N1 VIRUS-VACCINES IN SERONEGATIVE ADULT VOLUNTEERS [J].
SNYDER, MH ;
CLEMENTS, ML ;
BETTS, RF ;
DOLIN, R ;
BUCKLERWHITE, AJ ;
TIERNEY, EL ;
MURPHY, BR .
JOURNAL OF CLINICAL MICROBIOLOGY, 1986, 23 (05) :852-857
[29]   THE COMPLETE NUCLEOTIDE-SEQUENCE OF 2 COLD-ADAPTED, TEMPERATURE-SENSITIVE ATTENUATED MUTANT VACCINE VIRUSES (CP12 AND CP45) DERIVED FROM THE JS']JS STRAIN OF HUMAN PARAINFLUENZA VIRUS TYPE-3 (PIV3) [J].
STOKES, A ;
TIERNEY, EL ;
SARRIS, CM ;
MURPHY, BR ;
HALL, SL .
VIRUS RESEARCH, 1993, 30 (01) :43-52
[30]   Recovery of a fully viable chimeric human parainfluenza virus (PIV) type 3 in which the hemagglutinin-neuraminidase and fusion glycoproteins have been replaced by those of PIV type 1 [J].
Tao, T ;
Durbin, AP ;
Whitehead, SS ;
Davoodi, F ;
Collins, PL ;
Murphy, BR .
JOURNAL OF VIROLOGY, 1998, 72 (04) :2955-2961