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Enterovirus 71 infection causes severe pulmonary lesions in gerbils, meriones unguiculatus, which can be prevented by passive immunization with specific antisera.

Xu F, Yao PP, Xia Y, Qian L, Yang ZN, Xie RH, Sun YS, Lu HJ, Miao ZP, Li C, Li X, Liang WF, Huang XX, Xia SC, Chen ZP, Jiang JM, Zhang YJ, Mei LL, Liu SL, Gu H, Xu ZY, Fu XF, Zhu ZY, Zhu HP - PLoS ONE (2015)

Bottom Line: However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models.Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination.EV71 viral titer was found to be peak at late stages of infection.

View Article: PubMed Central - PubMed

Affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.

ABSTRACT
Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs.

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The reciprocal neutralizing antibody and fluorescent antibody titers of EV71-specific serum in infected gerbils following IP inoculation with 1×105.5 TCID50 EV71.The solid line indicates mean antibody titer from three gerbils per group on a logarithmic scale for each day. Error bars represent the standard deviation.
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pone.0119173.g005: The reciprocal neutralizing antibody and fluorescent antibody titers of EV71-specific serum in infected gerbils following IP inoculation with 1×105.5 TCID50 EV71.The solid line indicates mean antibody titer from three gerbils per group on a logarithmic scale for each day. Error bars represent the standard deviation.

Mentions: Considering 7, 14, and 21 day-old gerbils infected via the IP route, all gerbils died before antibodies could be detected, we used 50-day-old gerbils for antibody detection. Eight gerbils were inoculated via the IP route with 1×105.5 TCID50 EV71, and neutralizing antibodies were detected as early as day five days p.i. and peaked at 28 days p.i. at a ratio of 1:75.39 (Fig. 5).


Enterovirus 71 infection causes severe pulmonary lesions in gerbils, meriones unguiculatus, which can be prevented by passive immunization with specific antisera.

Xu F, Yao PP, Xia Y, Qian L, Yang ZN, Xie RH, Sun YS, Lu HJ, Miao ZP, Li C, Li X, Liang WF, Huang XX, Xia SC, Chen ZP, Jiang JM, Zhang YJ, Mei LL, Liu SL, Gu H, Xu ZY, Fu XF, Zhu ZY, Zhu HP - PLoS ONE (2015)

The reciprocal neutralizing antibody and fluorescent antibody titers of EV71-specific serum in infected gerbils following IP inoculation with 1×105.5 TCID50 EV71.The solid line indicates mean antibody titer from three gerbils per group on a logarithmic scale for each day. Error bars represent the standard deviation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359154&req=5

pone.0119173.g005: The reciprocal neutralizing antibody and fluorescent antibody titers of EV71-specific serum in infected gerbils following IP inoculation with 1×105.5 TCID50 EV71.The solid line indicates mean antibody titer from three gerbils per group on a logarithmic scale for each day. Error bars represent the standard deviation.
Mentions: Considering 7, 14, and 21 day-old gerbils infected via the IP route, all gerbils died before antibodies could be detected, we used 50-day-old gerbils for antibody detection. Eight gerbils were inoculated via the IP route with 1×105.5 TCID50 EV71, and neutralizing antibodies were detected as early as day five days p.i. and peaked at 28 days p.i. at a ratio of 1:75.39 (Fig. 5).

Bottom Line: However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models.Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination.EV71 viral titer was found to be peak at late stages of infection.

View Article: PubMed Central - PubMed

Affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.

ABSTRACT
Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs.

Show MeSH
Related in: MedlinePlus