Monkeypox virus mutates at a higher rate

Monkeypox virus mutates at a higher rate

The mutation pattern does not conclusively prove human-to-human transmission

The mutation pattern does not conclusively prove human-to-human transmission

As of June 1, 2022, more than 550 laboratory-confirmed cases of monkeypox have been reported from 30 countries, the World Health Organization said in a press briefing. These countries are mostly located in Europe and North America, which is not an epidemic of monkeypox virus. With 190 cases as of May 30, the UK outbreak was the largest to date, with Spain (132 cases) and Portugal (132 cases) the other countries with a high number of monkeypox cases.

The World Health Organization confirmed again that the large number of cases detected in more than twenty countries over a short period of time indicates that “there may have been undetected transmission for some time”. Cases have been reported mostly among men who have had sex with symptomatic men in sexual health clinics.

Rave parties in Belgium and Portugal turned into super-popular events. In a statement issued on May 31, 2022, the European Union stressed the link between these parties and the issues. “Several countries have reported cases that appear to be linked to events in Spain (Madrid and Canary Islands) and Belgium (Antwerp),” she said.

However, cases have been reported of people who have no epidemiological link to delirium, travel history to countries in Africa or even contact with other infected people, the statement noted.

very speculative

Although the first case discovered on May 7, 2022 in the UK was in a person who had just returned from Nigeria, samples were collected from at least two people, one in Canada and the other in Portugal, before the return of a British person who had tested positive for smallpox virus. monkeys.

Christian Happy of the African Center for Excellence in Infectious Disease Genomics in Nigeria said the idea that the virus may have been imported from Nigeria is “extremely speculative”. Sciences.

Epidemiologist Evidio Aditiva, head of the Nigeria Center for Disease Control, said: Sciences That “there is too much focus for whatever reason in Western capitals and the media around trying to hold someone responsible for a particular disease outbreak. We don’t think these accounts are helpful.”

So far in 2022, seven African countries have reported 1,392 suspected and 44 confirmed cases of monkeypox to the WHO, just under half of the cases reported last year.

47 mutation

Meanwhile, Dr Andrew Rambaut of the University of Edinburgh has found 47 mutations in the virus’ genome based on sequencing analysis of the current outbreak outside Africa and comparing it to previous genomes from samples from patients in 2017-19 in Singapore, Israel, Nigeria and the United Kingdom.

“47 replaced in three to four years is an unexpectedly large number. As MPXV [monkeypox virus] Considered an animal virus with limited human-to-human transmission, this long branch may be evidence of adaptation to humans allowing sustained transmission that is now being observed,” he said at

But Dr Vinod Skaria, chief scientist at the Delhi Institute of Genomics and Integrative Biology (CSIR-IGIB), says the mutation rate of monkeypox virus has not been well established.

“The number (about two per year) comes from the limited data from other poxviruses studied,” he explains. “The inaccuracy also stems from the fact that monkeypox virus is primarily a zoonotic disease and that its genomes have not previously come from sustained human-to-human transmission in the past.”

About the 47 mutations that appear in the genome and are now sequenced, he says, “while the number of mutations appears significantly larger than expected, this could mean many things — mutation rate estimates for monkeypox can vary across hosts (animals vs. humans), and many intermediate pathways of evolution and their representatives have not been sequenced to ascertain precisely the evolutionary path of these specific isolates.”

Continuous transmission?

According to Dr. Rambaut, many mutations arise due to the action of a specific enzyme present in the host to prevent the virus from reproducing. Based on the mutation pattern seen in the genome of the virus isolated from people since 2017, it “indicates replication in humans,” says Dr. Rambaut. And “inheriting the specific changes that occurred between 2017 and 2018, and then in viruses from 2022 means that there has been continuous human-to-human transmission since at least 2017.”

However, Dr. Sakarya is not convinced that the presence of the mutation pattern indicates continuous human-to-human transmission.

He says, “Evidence indicates that many mutations match the profile of a unique set of enzymes. Whether it is in the primary host, an unknown intermediate host or in humans is still unknown and something that is difficult to prove conclusively with the existing data, as we do not have genomes It spans the period between the last major outbreak so far.”

While the presence of 47 mutations indicates that monkeypox virus is mutating at a much higher rate than the previously thought rate of two to three mutations per year, the mutations do not necessarily indicate that monkeypox virus is becoming more transmissible, says Dr. Scaria. .

“The mutations we see don’t change the amino acids in the protein. All adaptations to evolutionary pressure usually happen because of changes in the amino acids that we don’t see here. This suggests that the mutations we see are leftovers of enzyme action and not necessarily an evolutionary process or adaptations of the virus,” he explains. Dr.. Scaria.

“Also, unlike SARS-CoV-2, which depends on a specific receptor to enter cells, monkeypox viruses do not depend on receptors for cell entry. So some mutations are unlikely to significantly increase infection.”

But the presence of 47 mutations in the virus indicates continuous transmission in the past four or five years.

But we don’t know for sure whether the virus collected these mutations in humans or in animals. We do not have the virus’ genomes sequenced at intermediate time intervals between 2017 and 2022, so we cannot say for certain whether or not sustained transmission has occurred in humans.

higher rate

But the large group of mutations clearly indicates that the previous notion of a mutation rate of two to three per year for monkeypox virus is a gross understatement. The monkeypox virus is already evolving at a higher rate than previously assumed.

The 47 mutations seen in the genome sequence indicate that the virus was able to collect these mutations in a short period of time.

This change in mutation pattern likely indicates a transition from the original host to humans or an intermediate host where a host enzyme (possibly APOBEC3) may alter the genome. The rate of change increased from 10 to 20 times and is now about one change per month,” Dr. Richard Nir of the University of Basel chirp. “We don’t know what these mutations do. The vast majority of them are probably not significant or harmful to the virus and we have no evidence of viral adaptation. But they will help us distinguish between the different groups of monkeypox outbreaks and understand how the virus spreads.”

2022-06-04 14:00:00

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