Pathogenicity and Virulence of Ebolaviruses with Species- and Variant-specificity

Figures & data

Figure 1. Genomic organization and viral particle of ebolaviruses. The single-stranded, negative-sense genome consists of a linear RNA molecule of approximately 19 kb that is composed of seven genes: NP, VP35, VP40, GP, VP30, VP24, and L. The viral particles are filamentous in shape, consisting of a nucleocapsid core surrounded by a viral matrix protein VP40 and a host-derived envelope studded with GP spikes

Figure 2. Ebola disease outbreaks and case fatality rates (CFRs) of EBOV, SUDV, and BDBV infections. Forest plot shows the average CFRs and 95% confidence intervals (CIs) for the Ebola disease outbreaks by fixed-effect model with inverse-variance weighting. Meta-analysis was performed using R software with the metaphor package. The CFRs from the 2013–2016 EVD outbreak caused by EBOV-Makona variant is separately calculated from the average CFRs from all other EVD cases. N.A: not available due to small sample size

Figure 3. Species-specific and variant-specific virulence of ebolaviruses. Viral ability to spread from macrophages to parenchymal cells, leading to severe organ damage, is one of the key phenotypic features determining ebolavirus pathogenicity. The numbers 1–6 shown in a table on the right are correlated with those shown in a figure on the left. *Including Kupffer cells. na: not available

Table 1. Comparison of fatality rates and time to deaths in animal models infected with different ebolaviruses

	EBOV				SUDV	BDBV	TAFV	RESTV	Refs.
	Mayinga	Kikwit	Makona (early)	Makona (late)
NHPs	100% (5–7 d)	100% (3–5 d)	100% (4–10 d)	100% (8–16 d)	50–100% (9–10 d)	50–75% (10–13 d)	60% (10–14 d)	80–100% (8–21 d)	[6,136–139,141–145,192,194,198]
Ferrets	na	100% (6 d)	100% (6–7 d)	na	100% (6–9 d)	100% (8–9 d)	na	na	[78,150,151,198,199]
HIS mice*	87–100% (8–20 d)	na	50–56% (13–22 d)	100% (9–11 d)	71% (11–19 d)	29% (17–18 d)	18% (11–13 d)	20% (13–20 d)	[93,94,96–98]
IFNAR^−/- mice	100% (5–6 d)	0–7% (6 d)	0–40% (9 d)	0%	5–100% (6–11 d)	0%	0%	0%	[90,91,192,193,199]

Virus inoculation route and dose varied among each publication. na: not available.

*Except for NSG-huPBL mice.

Table 2. Comparison of pathogenic functions of viral proteins among ebolaviruses

Protein	Pathogenic function	EBOV	SUDV	BDBV	TAFV	RESTV	Refs.
RNP complex	Genome replication/transcription*	+++	na	na	na	+	[158,160]
GP	NF-κB activation	+++	na	na	na	+	[127–131]
VP35	Inhibition of type I IFN induction	+++	+++	+++	+++	+++	[101–110,166–169]
VP24	Inhibition of ISG expression	+++	na	+	na	+++	[114–117,170]

na: not available.

*Assessed by ebolavirus minigenome system.

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