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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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Histological examinations of lung in 21-day-old gerbils challenged with humane doses 100×HD50 EV71.(A) Gerbils receiving EV71-antisera revealed no evidence of inflammation and structures of the lungs appeared intact. (B) Gerbils receiving the mock sera, lung structures were damaged and multiple foci of pulmonary interstitial inflammatory were observed. Hematoxylin and eosin stain; magnification: A, B 200x.
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pone.0119173.g007: Histological examinations of lung in 21-day-old gerbils challenged with humane doses 100×HD50 EV71.(A) Gerbils receiving EV71-antisera revealed no evidence of inflammation and structures of the lungs appeared intact. (B) Gerbils receiving the mock sera, lung structures were damaged and multiple foci of pulmonary interstitial inflammatory were observed. Hematoxylin and eosin stain; magnification: A, B 200x.

Mentions: Passive immunization was used to evaluate the effects of humoral immunity in protecting against EV71 lethal challenge. Gerbils were passively immunized with neutralizing antibodies (GMT = 89; 100 μL/gerbil). Two doses fully protected gerbils from EV71 lethal challenge. In contrast, mock-immunized gerbils developed hind limb paralysis and were dead at 5–6 days post-challenge (Fig. 6). Histological examination indicted gerbils that received the anti-EV71 antibodies had intact lung structures without detected EV71-induced lesions and no virus copies were detected in lungs by real-time RT-PCR. Mock-immunized gerbils revealed severe lung pathology including pulmonary interstitial inflammatory infiltration and alveolar septum broadening (Fig. 7). These results demonstrate passively acquired protection against EV71-induced lung lesions in the gerbil model is mediated by specific antisera containing neutralizing antibodies to EV71.


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)

Histological examinations of lung in 21-day-old gerbils challenged with humane doses 100×HD50 EV71.(A) Gerbils receiving EV71-antisera revealed no evidence of inflammation and structures of the lungs appeared intact. (B) Gerbils receiving the mock sera, lung structures were damaged and multiple foci of pulmonary interstitial inflammatory were observed. Hematoxylin and eosin stain; magnification: A, B 200x.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4359154&req=5

pone.0119173.g007: Histological examinations of lung in 21-day-old gerbils challenged with humane doses 100×HD50 EV71.(A) Gerbils receiving EV71-antisera revealed no evidence of inflammation and structures of the lungs appeared intact. (B) Gerbils receiving the mock sera, lung structures were damaged and multiple foci of pulmonary interstitial inflammatory were observed. Hematoxylin and eosin stain; magnification: A, B 200x.
Mentions: Passive immunization was used to evaluate the effects of humoral immunity in protecting against EV71 lethal challenge. Gerbils were passively immunized with neutralizing antibodies (GMT = 89; 100 μL/gerbil). Two doses fully protected gerbils from EV71 lethal challenge. In contrast, mock-immunized gerbils developed hind limb paralysis and were dead at 5–6 days post-challenge (Fig. 6). Histological examination indicted gerbils that received the anti-EV71 antibodies had intact lung structures without detected EV71-induced lesions and no virus copies were detected in lungs by real-time RT-PCR. Mock-immunized gerbils revealed severe lung pathology including pulmonary interstitial inflammatory infiltration and alveolar septum broadening (Fig. 7). These results demonstrate passively acquired protection against EV71-induced lung lesions in the gerbil model is mediated by specific antisera containing neutralizing antibodies to EV71.

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