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.

Genetic characteristics of the P1 coding region of Coxsackievirus A16 associated with hand, foot, and mouth disease in China

“…VP1, VP2, and VP3 capsid proteins are exposed on the viral surface, while VP4 is usually situated on the inner portion. There are many B-lymphocyte antigenic epitopes and virulence-associated sites in the viral structural proteins [26][27][28][29][30]. Investigations into the geographical distribution and genetic characteristics of the gene in the P1 coding region of CVA16 associated with HFMD in China may provide basic information for the prevention and control of HFMD.…”

Pathological and molecular studies on Coxsackie virus A‐16 isolated from hand, foot, and mouth disease cases in India: Approach using neonatal mouse model

“…Clinical signs appeared in ICR mice showed weight loss, difficulty in movement, hunched posture, and limb paralysis. The severity of the clinical disease was scored as 0: healthy; 1: lethargy and inactivity; 2: wasting; 3: limb shaking weakness; 4: hind limb paralysis, and 5: moribund/dead . The limb paralysis was found on day 5 of PID.…”

“…To understand the susceptibility of mice strains to CVA-16/311 virus, Swiss albino and ICR (Institute of Cancer Research) mice strains were selected. 19 In the study, comparison to check the susceptibility of different mice strains which include ICR mice and Swiss albino for CVA-16/311 infection was conducted. It was observed that as compared to Swiss albino, ICR mice are more susceptible to CVA-16/ 311 infection.…”

“…The severity of the clinical disease was scored as 0: healthy; 1: lethargy and inactivity; 2: wasting; 3: limb shaking weakness; 4: hind limb paralysis, and 5: moribund/dead. 8,19 The limb paralysis was found on day 5 of PID.…”

柯萨奇病毒b4诱导急性心肌炎和大脑皮层神经元水肿小鼠模型的建立

“…In addition, readily discernible pathological changes were detected in both brain and myocardial tissue. Compared with enterovirus species A virus infection models, including EV-A71 ( Dong et al, 2016 ; Yue et al, 2016 ), CV-A16 ( Huang et al, 2015 ; Mao et al, 2012 ), CV-A6 ( Zhang et al, 2017b ), and CV-A10 ( Zhang et al, 2017a ), which are associated with hind limb paralysis and/or severe respiratory involvement, the enterovirus species B CV-B4 had comparably minor pathology in skeletal muscle and lung tissue.…”