Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans

Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans
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DOI:
10.1371/journal.pone.0139481
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发表时间:
2015-10-08
期刊:
影响因子:
3.7
通讯作者:
Suhrbier, Andreas
Suhrbier, Andreas
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gardner, Joy;Rudd, Penny A.;Suhrbier, Andreas

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基孔肯雅病毒(CHIKV)是一种重新出现的甲病毒,通常由蚊子传播,偶尔会在人类患者中产生出血表现,例如鼻子出血和牙龈出血。干扰素应答因子3和7缺陷(IRF 3/7(-/-))小鼠,其缺乏干扰素a/a应答,在CHIKV感染后可靠地发展出血表现。在这里,我们表明感染性病毒存在于CHIKV感染的IRF 3/7(-/-)小鼠的口腔中,这可能是由于嗅觉上皮中的出血性病变,其允许受感染的血液流出到鼻腔中,随后进入口腔。此外,IRF 3/7(-/-)小鼠更容易通过鼻内和口服途径感染CHIKV,IRF 3/7(-/-)小鼠也能够在没有节肢动物载体的情况下在小鼠之间传播病毒。食蟹猴在CHIKV感染后经常表现出牙龈出血,对几只感染猴的唾液进行分析也发现了病毒RNA和感染性病毒的存在。此外,发现从几个具有出血表现的急性CHIKV患者收集的唾液样品含有病毒RNA和感染性病毒。因此,在急性CHIKV感染期间,口腔液可能是传染性的,这可能是由于口腔/鼻腔中的出血表现。
Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7(-/-)) mice, which are deficient for interferon a/a responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7(-/-)mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7(-/-) mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7(-/-) mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.