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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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Survival rates of gerbils infected with EV71.(A) Gerbils (7, 14, 21, 28, and 35 d old) were inoculated IP with 1x105.5 TCID50 of EV71 (n = 6 for each age group). (B) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×105.5 TCID50 of EV71 via IP, IM or OL respectively.
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pone.0119173.g001: Survival rates of gerbils infected with EV71.(A) Gerbils (7, 14, 21, 28, and 35 d old) were inoculated IP with 1x105.5 TCID50 of EV71 (n = 6 for each age group). (B) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×105.5 TCID50 of EV71 via IP, IM or OL respectively.

Mentions: In order to examine the susceptibility of gerbils at different ages to EV71 infection, three groups of gerbils at the age of 7, 14 and 21 days were IP inoculated with 1×105.5 TCID50 of EV71 (n = 6 for each age groups). All gerbils presented with a sudden onset of symptoms at 3–4 days post-inoculation. In addition, all gerbils showed disease signs including progressing weakness, one or two hind limb paralysis and deep lethargy. Illness progressed rapidly and usually caused death within 12 hours of onset. Ten gerbils (two in 7 days, four in 14 days and four in 21 days of age) also had respiratory system symptoms including tachypnea, respiratory distress, apnea, or rhythm changes. Clinical signs between the three age groups were not different, with the only variation of the time from EV71 inoculation to disease onset. The average time of disease onset and death was 3 and 3.7 p.i., respectively, for gerbils in the 7-day-old group. For gerbils in the 14-day-old or 21-day-old groups, the average time of disease onset was 4–5 days and death occurred within 6–12 h after clinical signs occurred. In the 28-day-old group, two of out six gerbils began to exhibit hind limb weakness and paralysis five days post-IP inoculated with 1×105.5 TCID50 of EV71 and died two days later. Four gerbils survived and one experienced hind limb paralysis. There was no mortality in the 35-day-old group with only two gerbils presenting with hind limb paralysis (Fig. 1A, S1–S5 Tables). These data demonstrated that gerbils aged 7–21 days were most sensitive to the EV71 infection.


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)

Survival rates of gerbils infected with EV71.(A) Gerbils (7, 14, 21, 28, and 35 d old) were inoculated IP with 1x105.5 TCID50 of EV71 (n = 6 for each age group). (B) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×105.5 TCID50 of EV71 via IP, IM or OL respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119173.g001: Survival rates of gerbils infected with EV71.(A) Gerbils (7, 14, 21, 28, and 35 d old) were inoculated IP with 1x105.5 TCID50 of EV71 (n = 6 for each age group). (B) 21-day-old gerbils were inoculated with 1×103.5 or 1×105.5 TCID50 of EV71 via IP (n = 8 for each dose group). (C) 21-day-old gerbils were inoculated with 1×105.5 TCID50 of EV71 via IP, IM or OL respectively.
Mentions: In order to examine the susceptibility of gerbils at different ages to EV71 infection, three groups of gerbils at the age of 7, 14 and 21 days were IP inoculated with 1×105.5 TCID50 of EV71 (n = 6 for each age groups). All gerbils presented with a sudden onset of symptoms at 3–4 days post-inoculation. In addition, all gerbils showed disease signs including progressing weakness, one or two hind limb paralysis and deep lethargy. Illness progressed rapidly and usually caused death within 12 hours of onset. Ten gerbils (two in 7 days, four in 14 days and four in 21 days of age) also had respiratory system symptoms including tachypnea, respiratory distress, apnea, or rhythm changes. Clinical signs between the three age groups were not different, with the only variation of the time from EV71 inoculation to disease onset. The average time of disease onset and death was 3 and 3.7 p.i., respectively, for gerbils in the 7-day-old group. For gerbils in the 14-day-old or 21-day-old groups, the average time of disease onset was 4–5 days and death occurred within 6–12 h after clinical signs occurred. In the 28-day-old group, two of out six gerbils began to exhibit hind limb weakness and paralysis five days post-IP inoculated with 1×105.5 TCID50 of EV71 and died two days later. Four gerbils survived and one experienced hind limb paralysis. There was no mortality in the 35-day-old group with only two gerbils presenting with hind limb paralysis (Fig. 1A, S1–S5 Tables). These data demonstrated that gerbils aged 7–21 days were most sensitive to the EV71 infection.

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