New study shows Mpox has been spreading silently in countries not endemic to smallpox for 20 years

In a recent study published in Emerging infectious diseasesResearchers describe the evolution of the mpox virus (MPXV) before the 2022 outbreak.

Study: Evolution of monkeypox virus before the 2022 outbreak. Image credit: Marina Demidiuk / Shutterstock
Stady: The evolution of monkeypox virus before 2022 break out Image credit: Marina Demidiuk / Shutterstock


Mpoxvirus is a double-stranded ribonucleic acid (DNA) virus that has led to outbreaks that are often brief and self-limited due to inefficient human transmission. Preliminary epidemiological investigations have shown persistent human-to-human transmission in non-endemic European countries through intimate contacts, such as sexual networks.

Portugal announced the first MPXV genome sequence from the pandemic on May 19, 2022, and there are several sequences that provide information on virus transmission. Early genetic analysis suggested that the virus responsible for the 2022 MPXV outbreak was from MPXV clade II, which was found to be less virulent than clade I. This suggests that recent introduction of MPXV into communities from non-MPXV-endemic countries triggered the outbreaks. However, extensive research is needed to determine the exact evolutionary process of MPXV.

Phylogenetic examination of MPXV

Phylogenetic analysis of approximately 105 MPXV genomes indicated that the 2022 viruses belong to two cascades that can be associated with the recent pandemic in 2017-2018. All 2022 viral genomes consist of a vast monophyletic group, although significant sequence divergence has been identified across strains with many subclones appearing. This divergence is inconsistent with the rapid diversification of the virus over the past several months of the 2022 outbreak. Instead, it represented a small, continuous evolution since the outbreak of 2017-2018.

Like the most recent common ancestor (MRCA) of the 2017-2018 pandemic, the MRCA of the outbreak in 2022 can be traced back nearly 20 years. In addition, the 2022 outbreak of MPXVs was more associated with strains exported from Africa at the time of the last outbreak than with strains prevalent in Nigeria around that time. In addition, the strain from an individual traveling to the United States from Nigeria in 2021 could also be linked to the source of the outbreak in 2022. Since the outbreak occurred in 2017-2018, the most likely assumption was that MPXV had spread silently and undetected in several countries. Not endemic with MPXV outside Africa.

Genomic alterations in MPXV

Multiple genetic alterations were identified in prevalent MPXVs in 2022. At least 51 single nucleotide polymorphisms (SNPs) and some larger deletions/insertions distinguished the initial 18 viral genomes observed in the 2022 pandemic from those detected in 2017–2018. Of the 52 SNPs, 26 SNPs resulted in amino acid alterations, while 21 were synonymous substitutions. More SNPs would have been detected in genetic sequences from 2022, which would explain the variation observed within the epidemic. Future research can help determine the phenotypic effects of these modifications, which may be related to mutational pressure and adaptability.

The team also noted that prior to 2018, viruses of both MPXV variants had roughly similar amounts of substitution species, and by 2022, the fraction of guanine (G) > adenine (A)/cytosine (C) > thymine (T) transitions within the viruses multiplied. clade II. Presumably, the significant substitution modifications reflect the editing ability exhibited by the mRNA-editing enzyme, catalytic subunit 3G (APOBEC3G) enzyme, which catalyzed strand-specific C>uracil (U) substitutions and led to G>A substitutions in complementary strands. for the viral genome.


The results of the study indicated that MPXV had been circulating silently for nearly 20 years, likely in many non-MPXV-endemic countries outside of Africa. In addition, the pattern of nucleotide substitution showed a distinct genetic feature of a recent host alteration. These findings could have significant public health implications as the epidemiological shift associated with MPXV infection and viral circulation in humans in non-endemic countries with MPXV necessitate tighter surveillance.

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