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mRNA Encoding IL-2 Mutein Is Used to Treat Autoimmune Diseases
1. Nature Medicine: Monkeypox virus seems to be accelerating evolution
Portuguese researchers analyzed the genome of monkeypox virus (MAPX) outbreaks in
multiple countries and found that these samples clustered together, indicating that they had
a single source.
According to the World Health Organization, more than 2,500 laboratory-confirmed
monkeypox cases have been reported worldwide from the beginning of this year to mid-June,
most of which were reported in the past two months. More than 80% of the cases were
reported from Europe and 12% from the Americas, whereas most of these cases had no known
association with endemic areas.
Researchers recently carried out phylogenetic analysis of 2022 MPXV and found that this
outbreak may have a single source and is associated with a large-scale epidemic in Nigeria
in 2017. They report in Nature Medicine that viral samples appear to be accelerating evolution,
which may be affected by host APOBEC3, a host antiviral mechanism.
"Accelerated evolution is an observation, but we do not yet know how this occurs," said senior
author João Paulo Gomes of the Portuguese National Institute of Health. It was completely
unexpected to find so many mutations in 2022 MPXV. "
Gomes and colleagues analyzed their first 2022 MPXV genome released on May 19, as well
as 14 other MPXV genome sequences, most of which were also from Portugal.
Phylogenetic analysis placed all samples from the 2022 outbreak in clade 3, the part formerly
called the "West African" clade. All samples clustered tightly together, suggesting a single
source of the outbreak.
At the same time, these samples also formed a clade that differed from the viruses carried by
the UK, Israel, and Singapore cases in 2018 and 2019. This suggests that the epidemic in 2022
may have resulted from the continued spread and evolution of the Nigerian virus.
However, the monkeypox virus in 2022 differed by an average of 50 SNPs from the 2018/2019
virus, which Gomes believes is much more than expected. He says for this type of virus, one
or two mutations are expected each year. Because the 2022 virus is the "descendant" of the
2017 Nigerian virus, they expect approximately 5 to 10 mutations, rather than 50.
"Therefore, there is no doubt that we are facing accelerated evolution," Gomes said.
The researchers point out that these changes also tend to follow a pattern that incorporates
more adenine A and thymine T into already A/T-rich viral genomes, suggesting that the
human APOBEC3 system may be involved in this accelerated evolution.
APOBEC3 is a host antiviral mechanism that can induce viral mutations and has the potential
2. to cause hypermutation if the enzyme does not fully restrict the virus. Gomes points out that
this mechanism has already been found in HIV and HPV.
"We don't know what the consequences are, but we find that some mutations are affecting
viral proteins that interact with the human immune system, so the mechanism of immune
escape cannot theoretically be completely abandoned," he added.
Overall, the researchers say viral genome sequencing can help scientists better understand
the mode of transmission of the 2022 monkeypox virus and deeply explore ways to control
this transmission. "We will continue to identify and monitor mutations that appear in real time
during transmission in order to better understand host adaptation," Gomes said.