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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.


Dose-dependent survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. Curves were compared with the 0.3 TCID50 group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. One representative of two independent experiments was shown in A and B.
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f2: Dose-dependent survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. Curves were compared with the 0.3 TCID50 group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. One representative of two independent experiments was shown in A and B.

Mentions: In order to further evaluate 21-day-old gerbils as a suitable CA16 infection model, gerbils were infected with a TCID50 ranging between 105.5 and 0.32 using CA16-194. Gerbils infected with higher doses, TCID50 of 102.5 and above, all died within four to seven days after infection (Fig. 2A), while clinical symptoms appeared at three to four days post-infection (Fig. 2B). At lower doses of CA16-194, onset of symptoms was retarded and survival of the gerbils was increased. Finally, at a TCID50 of 0.32, all gerbils survived and remained fully healthy. Based on these results, the 50% lethal dose (LD50) was calculated to be 3.16 × 101.0 TCID50. These results showed that the disease severity and clinical outcome of CA16-infected gerbils were correlated with the dose of infection.


Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation
Dose-dependent survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. Curves were compared with the 0.3 TCID50 group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 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

f2: Dose-dependent survival and severity of disease in CA16-infected gerbils.(A) Survival curves for groups of gerbils (n = 8–10) aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. Curves were compared with the 0.3 TCID50 group using the log-rank test. *Significantly different from the control group (p < 0.01). (B) Mean clinical scores for groups of gerbils aged 21 days when infected with CA16-194 at a TCID50 of 0.3 to 105.5. One representative of two independent experiments was shown in A and B.
Mentions: In order to further evaluate 21-day-old gerbils as a suitable CA16 infection model, gerbils were infected with a TCID50 ranging between 105.5 and 0.32 using CA16-194. Gerbils infected with higher doses, TCID50 of 102.5 and above, all died within four to seven days after infection (Fig. 2A), while clinical symptoms appeared at three to four days post-infection (Fig. 2B). At lower doses of CA16-194, onset of symptoms was retarded and survival of the gerbils was increased. Finally, at a TCID50 of 0.32, all gerbils survived and remained fully healthy. Based on these results, the 50% lethal dose (LD50) was calculated to be 3.16 × 101.0 TCID50. These results showed that the disease severity and clinical outcome of CA16-infected gerbils were correlated with the dose of infection.

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.