Abstract
The filoviruses Ebola virus (EBOV) and Sudan virus (SUDV) can cause severe diseases, and there are currently no licensed countermeasures available for use against them. Transmission occurs frequently via contact with bodily fluids from infected individuals. However, it can be difficult to determine when or how someone became infected, or the quantity of infectious virus to which they were exposed. Evidence suggests the infectious dose is low, but the majority of published studies use high exposure doses. This study characterized the outcome of exposure to a low dose of EBOV or SUDV, using a Macaca fascicularis model. Further, because the effect of virus passage in cell culture may be more pronounced when lower exposure doses are used, viruses that possessed either the characteristics of wild type viruses (possessing predominantly 7-uridine (7U) genotype and a high particle-to-plaque forming unit (PFU) ratio) or cell culture-passaged viruses (predominantly 8-uridine (8U) genotype, a lower particle-to-PFU ratio) were used. The time to death after a low dose exposure was delayed in comparison to higher exposure doses. These data demonstrated that an extremely low dose of EBOV or SUDV is sufficient to cause lethal disease. A low dose exposure model can help inform studies on pathogenesis, transmission, and optimization of prevention strategies.
Highlights
The filoviruses Ebola virus (EBOV) and Sudan virus (SUDV) are enveloped, negative-sense, single-stranded, RNA viruses that can cause disease with high case fatality rates [1], and there are currently no licensed countermeasures available for use against them
Two different virus stocks were used for both EBOV and SUDV exposures: a 7U virus stock, or an 8U virus stock
There were no clear differences in anatomical pathology between the 7U and 8U exposure groups for both SUDV and EBOV, and findings were similar to what would be expected from exposure with a higher dose
Summary
The filoviruses Ebola virus (EBOV) and Sudan virus (SUDV) are enveloped, negative-sense, single-stranded, RNA viruses that can cause disease with high case fatality rates [1], and there are currently no licensed countermeasures available for use against them. In large outbreaks with sustained person-to-person transmission, it is often difficult to determine when or how an individual became infected, and it is almost impossible to determine what quantity of infectious virus a person was exposed to [6]. When patients are not acutely ill, viral loads can be low. These low loads are thought to be unimportant epidemiologically [5,7], but further study is needed to fully understand the implications of low dose exposures. A better understanding of the outcomes of exposure to a low dose is needed, given the evidence that filoviruses can persist within previously infected individuals for months [8]
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