Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans
Joy Gardner1, Penny A Rudd2, Natalie A Prow1
1Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, and the Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia.
Abstract:
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 α/β 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.
Insights
Chikungunya virus (CHIKV) can spread through oral fluids, especially in patients with bleeding symptoms. This study found infectious CHIKV in the saliva of infected mice, monkeys, and humans, highlighting a potential non-vector transmission route.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing reemerging outbreaks.
- Hemorrhagic manifestations, like nosebleeds and bleeding gums, occur in some CHIKV patients.
- Interferon response factor 3 and 7 deficient (IRF3/7-/-) mice exhibit severe hemorrhagic symptoms after CHIKV infection.
Purpose of the Study:
- To investigate the presence and infectiousness of CHIKV in oral fluids.
- To understand the role of hemorrhagic lesions in viral dissemination.
- To explore potential non-arthropod transmission routes of CHIKV.
Main Methods:
- Infection of IRF3/7-/- mice with CHIKV.
- Analysis of oral cavities and saliva from infected mice, cynomolgus macaques, and human patients.
- Detection of viral RNA and infectious CHIKV in oral fluid samples.
- Assessment of CHIKV susceptibility via intranasal and oral routes in IRF3/7-/- mice.
Main Results:
- Infectious CHIKV was detected in the oral cavities of CHIKV-infected IRF3/7-/- mice.
- Hemorrhagic lesions in the olfactory epithelium facilitated virus entry into the nasal and oral cavities.
- IRF3/7-/- mice showed increased susceptibility to intranasal and oral CHIKV infection and transmitted the virus mouse-to-mouse.
- Viral RNA and infectious CHIKV were identified in the saliva of infected macaques and human patients with hemorrhagic manifestations.
Conclusions:
- Oral fluids can be infectious during acute CHIKV infections, particularly when hemorrhagic manifestations are present.
- The oral cavity serves as a potential route for CHIKV transmission, independent of mosquito vectors.
- Findings suggest a need to consider oral fluid exposure in CHIKV prevention and control strategies.
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