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Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation

View Article: PubMed Central - PubMed

ABSTRACT

Coxsackievirus A16 (CA16) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) in the Asia-pacific region. Although CA16 infections are generally mild, severe neurological manifestations or even death has been reported. Studies on CA16 pathogenesis and vaccine development are severely hampered because the small animal models that are currently available show major limitations. In this study, gerbils (Meriones unguiculatus) were investigated for their suitability as an animal model to study CA16 pathogenesis and vaccine development. Our results showed that gerbils up to the age of 21 days were fully susceptible to CA16 and all died within five days post-infection. CA16 showed a tropism towards the skeletal muscle, spinal cord and brainstem of gerbils, and severe lesions, including necrosis, were observed. In addition, an inactivated CA16 whole-virus vaccine administrated to gerbils was able to provide full protection to the gerbils against lethal doses of CA16 strains. These results demonstrate that gerbils are a suitable animal model to study CA16 infection and vaccine development.

No MeSH data available.


Age-related survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. Curves were compared with the 7 days age group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. One representative of two independent experiments was shown in A and B.
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f1: Age-related survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. Curves were compared with the 7 days age group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. One representative of two independent experiments was shown in A and B.

Mentions: To investigate the correlation between the age of gerbils and their susceptibility to a CA16 infection, gerbils aged 7 to 56 days were inoculated via the intra-peritoneal (IP) route using clinical isolate CA16-194 at a 50% tissue culture infective dose (TCID50) of 105.5 per gerbil. Gerbils were monitored for survival and severity of clinical symptoms for 20 days (Fig. 1A). Gerbils up to 21 days of age all died within five days post-infection (Fig. 1A), which was the result of a rapid onset of clinical symptoms at three to four days post-infection (Fig. 1B). The percentage of survival increased with the age of infection and similarly, the clinical symptoms were also reduced in older gerbils. Finally, gerbils at 56 days of age did not show any clinical symptoms after infection with CA16-194 and hence, all gerbils survived. These results indicated that gerbils aged 21 days or younger were fully susceptible to a CA16 infection and owing to the long sensitive period, 21-day-old gerbils were selected for further analysis of their suitability as an animal model.


Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation
Age-related survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. Curves were compared with the 7 days age group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. One representative of two independent experiments was shown in A and B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035925&req=5

f1: Age-related survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. Curves were compared with the 7 days age group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 7 to 56 days when infected with CA16-194 at a TCID50 of 105.5. One representative of two independent experiments was shown in A and B.
Mentions: To investigate the correlation between the age of gerbils and their susceptibility to a CA16 infection, gerbils aged 7 to 56 days were inoculated via the intra-peritoneal (IP) route using clinical isolate CA16-194 at a 50% tissue culture infective dose (TCID50) of 105.5 per gerbil. Gerbils were monitored for survival and severity of clinical symptoms for 20 days (Fig. 1A). Gerbils up to 21 days of age all died within five days post-infection (Fig. 1A), which was the result of a rapid onset of clinical symptoms at three to four days post-infection (Fig. 1B). The percentage of survival increased with the age of infection and similarly, the clinical symptoms were also reduced in older gerbils. Finally, gerbils at 56 days of age did not show any clinical symptoms after infection with CA16-194 and hence, all gerbils survived. These results indicated that gerbils aged 21 days or younger were fully susceptible to a CA16 infection and owing to the long sensitive period, 21-day-old gerbils were selected for further analysis of their suitability as an animal model.

View Article: PubMed Central - PubMed

ABSTRACT

Coxsackievirus A16 (CA16) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) in the Asia-pacific region. Although CA16 infections are generally mild, severe neurological manifestations or even death has been reported. Studies on CA16 pathogenesis and vaccine development are severely hampered because the small animal models that are currently available show major limitations. In this study, gerbils (Meriones unguiculatus) were investigated for their suitability as an animal model to study CA16 pathogenesis and vaccine development. Our results showed that gerbils up to the age of 21 days were fully susceptible to CA16 and all died within five days post-infection. CA16 showed a tropism towards the skeletal muscle, spinal cord and brainstem of gerbils, and severe lesions, including necrosis, were observed. In addition, an inactivated CA16 whole-virus vaccine administrated to gerbils was able to provide full protection to the gerbils against lethal doses of CA16 strains. These results demonstrate that gerbils are a suitable animal model to study CA16 infection and vaccine development.

No MeSH data available.