Natural history of nonhuman primates after conjunctival exposure to Ebola virus
Robert W Cross1,2, Abhishek N Prasad1,2, Courtney B Woolsey1,2
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77550, USA.
Abstract:
Transmission of Ebola virus (EBOV) primarily occurs via contact exposure of mucosal surfaces with infected body fluids. Historically, nonhuman primate (NHP) challenge studies have employed intramuscular (i.m.) or small particle aerosol exposure, which are largely lethal routes of infection, but mimic worst-case scenarios such as a needlestick or intentional release, respectively. When exposed by more likely routes of natural infection, limited NHP studies have shown delayed onset of disease and reduced mortality. Here, we performed a series of systematic natural history studies in cynomolgus macaques with a range of conjunctival exposure doses. Challenge with 10,000 plaque forming units (PFU) of EBOV was uniformly lethal, whereas 5/6 subjects survived lower dose challenges (100 or 500 PFU). Conjunctival challenge resulted in a protracted time-to death compared to i.m. Asymptomatic infection was observed in survivors with limited detection of EBOV replication. Inconsistent seropositivity in survivors may suggest physical or natural immunological barriers are sufficient to prevent widespread viral dissemination.
Insights
Ebola virus (EBOV) conjunctival exposure in macaques showed that higher doses were lethal, while lower doses led to survival with delayed disease onset. This suggests natural barriers may prevent widespread Ebola virus dissemination.
Area of Science:
- Virology
- Infectious Diseases
- Primate Models
Background:
- Ebola virus (EBOV) transmission occurs through mucosal exposure to infected bodily fluids.
- Traditional nonhuman primate (NHP) studies use lethal intramuscular or aerosol routes, not reflecting natural infection.
- Limited studies on natural infection routes show delayed disease and reduced mortality.
Purpose of the Study:
- To systematically investigate Ebola virus (EBOV) pathogenesis via conjunctival exposure in cynomolgus macaques.
- To determine the dose-dependent lethality and disease progression following naturalistic EBOV exposure.
Main Methods:
- Cynomolgus macaques were challenged via conjunctival exposure with varying doses of EBOV (100-10,000 PFU).
- Disease onset, mortality, and viral replication were monitored.
- Survivors were assessed for seropositivity and signs of infection.
Main Results:
- High-dose (10,000 PFU) EBOV challenge was uniformly lethal.
- Lower doses (100 or 500 PFU) resulted in 5/6 survivors.
- Conjunctival exposure led to a longer time-to-death compared to intramuscular routes.
- Asymptomatic infections occurred in survivors with minimal viral replication detected.
- Seropositivity was inconsistent in survivors.
Conclusions:
- Conjunctival exposure to EBOV can be lethal at high doses but allows for survival at lower doses in cynomolgus macaques.
- Natural infection routes, like conjunctival exposure, result in protracted disease compared to intramuscular routes.
- Physical or immunological barriers may be sufficient to prevent widespread EBOV dissemination in some cases.
