Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo

Abstract

Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active disease surveillance has assessed monkeypox disease prevalence and geographic range, information about virus diversity is lacking. We therefore assessed genome diversity of viruses in 60 samples obtained from humans with primary and secondary cases of infection from 2005 through 2007. We detected 4 distinct lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that seemed to correlate with human-to-human transmission (p = 0.0544). The data suggest a high frequency of spillover events from the pool of viruses in nonhuman animals, active selection through genomic destabilization and gene loss, and increased disease transmissibility and severity. The potential for accelerated adaptation to humans should be monitored through improved surveillance.

Keywords: Democratic Republic of the Congo; Monkeypox virus; emerging infectious disease; gene loss; genomic diversity; genomic reduction; viruses.

Figure 1

Phylogenetic analysis of whole-genome direct sequencing. Evolutionary relationships between sequenced samples and archived monkeypox virus (MPXV) sequences were determined for the central coding region sequence (MPXV nucleotide positions ≈56000–120000). A cladogram representing the topology of an unrooted Bayesian phylogenetic reconstruction is shown for samples identified by sample number and/or GenBank accession number. The Central and Western African clades and the 4 distinct lineages are indicated. Confidence values for branching events were computed by Markov chain Monte Carlo convergence. Numbers at nodes represent Bayesian posterior probabilities computed by using MrBayes 3.1.2 (30).

Figure 2

Truncation of OMCP. A) Whole-genome deep sequencing revealed a 625-bp deletion directly upstream of the right ITR (red box), which completely removed MPV-Z-N2R (locus 201) and truncated OMCP (MPV-Z-N3R, locus 202). A Western African clade virus, MPXV-USA_2003_039, is shown for comparison with OMCP and N2R copy number. PCR amplification regions for the large deletion and the STRs (right and left) are indicated by the blue bar below each ITR diagram. The yellow box represents the ITR region, and all open reading frames are identified by their MPXV-COG_2003_358 locus number with genes of interest in parenthesis. B) Nucleotide alignment of the large deletion with MPXV-COG_2003_358 reference sequence. The truncated protein created by the deletion is indicated by the black background. ITR, inverted terminal repeat; MPXV, monkeypox virus; COG, Congo; STR, short terminal repeat; OMCP, orthopoxvirus major histocompatibility complex class I–like protein.