title: Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model.
abstract: An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Li
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Chang
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: G C
authors.initials: GC
authors.lastname: Liu
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: X F
authors.initials: XF
authors.lastname: Yu
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
authors.forename: W Y
authors.initials: WY
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence / Q000235:genetics; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D029821:Enterovirus A, Human / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D008813:Mice, Inbred ICR; D061251:Primary Cell Culture; D012367:RNA, Viral / Q000302:isolation & purification; D016415:Sequence Alignment; D013045:Species Specificity; D014611:Vaccination / Q000379:methods*; D014765:Viral Vaccines / Q000276:immunology*; D014774:Virulence; D014779:Virus Replication / Q000502:physiology*
chemical_list: D012367:RNA, Viral; D014765:Viral Vaccines
references.citation: Emerg Infect Dis. 2007 Jul;13(7):1084-6
references.pmid: 18214187
references.citation: J Virol Methods. 2009 Aug;159(2):233-8
references.pmid: 19490979
references.citation: Emerg Infect Dis. 2009 Oct;15(10):1689-91
references.pmid: 19861078
references.citation: J Virol. 2011 May;85(10):4937-46
references.pmid: 21389126
references.citation: Emerg Infect Dis. 2011 Aug;17(8):1537-40
references.pmid: 21801645
references.citation: PLoS One. 2012;7(3):e32405
references.pmid: 22479324
references.citation: Intervirology. 1978;9(1):60-3
references.pmid: 202573
references.citation: Emerg Infect Dis. 2014 May;20(5):913-5
references.pmid: 24751368
references.citation: J Gen Virol. 2014 May;95(Pt 5):1083-93
references.pmid: 24496826
references.citation: Hum Vaccin Immunother. 2014;10(2):360-7
references.pmid: 24231751
references.citation: Cleve Clin J Med. 2014 Sep;81(9):537-43
references.pmid: 25183845
references.citation: Pediatr Infect Dis J. 2004 Mar;23(3):275-6
references.pmid: 15014311
references.citation: PLoS One. 2014;9(4):e94746
references.pmid: 24736564