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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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Virus replication in lung and other tissues of EV71-infected gerbils.(A) gerbils (7, 14, 21, 28, 35 d old) were inoculated IP with 1×105.5 TCID50 of EV71 (n = 6 for each age groups). (B) Virus titer in various tissues was determined in 21-day-old gerbils inoculated with 1×105.5 TCID50 of EV71 via IP route (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP.
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pone.0119173.g004: Virus replication in lung and other tissues of EV71-infected gerbils.(A) gerbils (7, 14, 21, 28, 35 d old) were inoculated IP with 1×105.5 TCID50 of EV71 (n = 6 for each age groups). (B) Virus titer in various tissues was determined in 21-day-old gerbils inoculated with 1×105.5 TCID50 of EV71 via IP route (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP.

Mentions: We examinated the viral replication in gerbils infected with a dose of 1×105.5 TCID50 by IP route in animals of five different ages. Virus isolated from the lung was detectable as early as one day p.i. with viral titers almost the same for 7–21 day-old gerbils. Further, this number was lower for 28–35 day old gerbils. Thereafter, virus titers increased gradually and reached a peak at the end of stage of EV71-infection in five age groups (Fig. 4A). In other tissues, such as liver, kidney, pancreas, stomach and spleen, virus replicated to the same level as that in lung tissues. The peak virus titers in the lung (1×105.75 TCID50) were lower than that in the spinal cord, brainstem or skeletal muscle, the location of the highest observed virus titer 1×107.5~8.25 TCID50 (Fig. 4B). Therefore, lung tissue was not the major target organ of EV71 infection in young gerbils. These data indicate that EV71 is a CNS- and muscle-tropic virus.


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)

Virus replication in lung and other tissues of EV71-infected gerbils.(A) gerbils (7, 14, 21, 28, 35 d old) were inoculated IP with 1×105.5 TCID50 of EV71 (n = 6 for each age groups). (B) Virus titer in various tissues was determined in 21-day-old gerbils inoculated with 1×105.5 TCID50 of EV71 via IP route (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP.
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Related In: Results  -  Collection

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

pone.0119173.g004: Virus replication in lung and other tissues of EV71-infected gerbils.(A) gerbils (7, 14, 21, 28, 35 d old) were inoculated IP with 1×105.5 TCID50 of EV71 (n = 6 for each age groups). (B) Virus titer in various tissues was determined in 21-day-old gerbils inoculated with 1×105.5 TCID50 of EV71 via IP route (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP.
Mentions: We examinated the viral replication in gerbils infected with a dose of 1×105.5 TCID50 by IP route in animals of five different ages. Virus isolated from the lung was detectable as early as one day p.i. with viral titers almost the same for 7–21 day-old gerbils. Further, this number was lower for 28–35 day old gerbils. Thereafter, virus titers increased gradually and reached a peak at the end of stage of EV71-infection in five age groups (Fig. 4A). In other tissues, such as liver, kidney, pancreas, stomach and spleen, virus replicated to the same level as that in lung tissues. The peak virus titers in the lung (1×105.75 TCID50) were lower than that in the spinal cord, brainstem or skeletal muscle, the location of the highest observed virus titer 1×107.5~8.25 TCID50 (Fig. 4B). Therefore, lung tissue was not the major target organ of EV71 infection in young gerbils. These data indicate that EV71 is a CNS- and muscle-tropic virus.

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