Origin and dispersal of Hepatitis E virus

Figures & data

Fig. 1 Worldwide distribution of HEV genotypes.

a Geographic distribution of the four major HEV genotypes (HEV-1 to HEV-4). b Geographic origin of complete Orthohepevirus A genomes analyzed in this study. The number of sequences deriving from each continent or region is reported in parentheses. The location where animal-infecting Orthohepevirus A were collected is also shown. c Schematic representation of the Orthohepevirus A genome. Positions refer to the Burma (GenBank accession: M73218) reference strain for genotype 1. Note that ORF4 has been described only in HEV-1 and not in other HEV genotypes²⁵. The regions we used in different analyses, as detailed in the text, are shown. The region we filtered from the Orthohepevirus A genome alignment is indicated. The location of the recombination breakpoint is also reported. MT methyltransferase, P papain-like cysteine protease, Hel helicase, RdRp RNA-dependent RNA polymerase, Y Y domain, HVR hypervariable region, also known as polyproline region (PPR); X, macro domain

Fig. 2 Phylogeographic analysis of Orthohepevirus A.

a Maximum clade credibility tree for Reg-1. Branches are colored according to inferred ancestral location; posterior support for inferred locations at relevant nodes is shown. b The topologies of the Reg-1 and Reg-2 trees are shown. Pie charts represent the ancestral location probability of the respective area. Probabilities were averaged over 100 BBM runs with a similar number of sequences from East Asia, South/South-East Asia, and Europe. In BBM analyses, combined regions appear because we allowed two areas per node. c Posterior probability distributions for the location of the Orthohepevirus A MRCA obtained using BEAST and BBM. Results refer to the Reg-2-short region

Fig. 3 Ancestral host range of Orthohepevirus A.

a Maximum clade credibility trees for Reg-1 and Reg-2. Branches are colored according to inferred ancestral host; posterior support for the host range of the MRCA is reported. b Posterior probability distributions of ancestral host state for the MRCA of the Orthohepevirus A phylogeny. Probabilities derive from 100 BBM runs with omission of character state information for 22 randomly sampled human sequences belonging to genotypes 3 and 4

Branch lengths and tMRCA estimates for the Orthohepevirus genus

	Length (substitution/site)		Expansion (CI)^a	tMRCA (ya)
Orthohepevirus
	GTR	aBS-REL (CI)		GTR	aBS-REL^b(CI)
Reg-1-short	45.99	91 009	1978.89	24 812	49 100 219
		(40 200–103 923)	(874.10–2 259.69)		(21 688 169–56 067 428)
Reg-2	36.54	168 856	4621.13	7300	33 734 249
		(122 782–380 992)	(3 360.21–10 426.72)		(24 529 533–74 115 056)
Orthohepevirus A
	GTR	aBS-REL		GTR	aBS-REL^b(LSD calculated)^c
Reg-1	14.22	60.13	4.23	1884	7969 (6795)
Reg-2	12.19	86.72	7.11	878	6242 (4596)

^a Total branch length expansion (aBS-REL/GTR + G)

^b tMRCA inferred by multipling the time obtained with the GTR + G model (and LSD) by branch length expansion

^c tMRCA estimated using aBS-REL branch lengths as an input for LSD

Fig. 4 Orthohepevirus A timescaled phylogenetic trees.

Timescaled phylogenetic tree estimated using the Reg-1 and Reg-2 regions are shown. Branch lengths represent the evolutionary time measured by the grids corresponding to the timescale shown at the tree base (in years). The tMRCA of selected nodes is reported with 95% confidence intervals. The time-frames of historical events mentioned in the text are reported

NairVPAnangSSubramaniCEndoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virusPLoS Pathog.201612e100552110.1371/journal.ppat.10055214817972

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