Smallpox was last seen in the world in Somalia in October 1977. The World Health Organization (WHO) declared smallpox eradication in 1980. Official sources claim that the virus is now only found in two high-security laboratories in Russia and the United States, where it is employed for study.
Despite the fact that poxviruses are no longer a direct threat to people, scientists are nevertheless fascinated by this virus family. Modified strains are utilized to cure cancer on the one hand, and they have highly exciting multiplication properties on the other.
The smallpox virus creates its own multiplication machine.
While many viruses rely heavily on the host cell’s metabolic resources for replication, poxviruses have their own molecular machinery encoded in their genome. Two enzymes are critical components of this machinery: DNA polymerase, which multiplies viral genes, and RNA polymerase, which transcribes viral genes into mRNA. For example, the RNA polymerase of the vaccinia poxvirus strain is a huge complex made up of 15 distinct protein subunits with various biochemical functions.
For the first time, a team of researchers from the Biocenter of the Julius-Maximilians University of Würzburg (JMU) has been able to observe the polymerase of vaccinia viruses at the atomic level. The scientists had previously published an atomic-resolution three-dimensional structure of the RNA polymerase. Utz Fischer, who holds the Chair of the Department of Biochemistry I at JMU, leads the team in charge of the project. The findings of their research have been published in the journal Nature Structure and Molecular Biology.
On an atomic scale, three-dimensional structures
“We combined isolated RNA polymerase with a fragment of DNA containing the promoter, which serves as the start signal for viral gene production. This DNA element was detected by the enzyme, and it began creating mRNA “explains Julia Bartuli, who is in charge of the study’s biochemical work. In collaboration with Bettina Böttcher from the Department of Biochemistry II, the samples were then studied in the cryo-electron microscope. Using current computational tools, the scientists were able to rebuild the three-dimensional structure of the sample down to the atomic scale based on the data acquired.
“One single sample we investigated in the microscope allowed us to reconstruct a total of six separate polymerase complexes, which we could finally designate to individual phases of the transcription process,” explains Clemens Grimm, who heads Fischer’s structural analysis group. “We can connect the different images like a movie and so portray the early transcription process with time resolution,” says the researcher.
Humans are still at risk from smallpox.
But why explore poxviruses if the virus that is so harmful to humans has already been eradicated? Professor Fischer responds that there are strong reasons for this: “A smallpox infection still has no reliable cure; the only way to avoid it is to get vaccinated. If the viral samples that still exist were to be distributed again, for as by a terrorist strike, they would infect a population that has never been immunized.”
Another potential hazard, according to scientist Utz Fischer, is zoonotic infections, which are caused by animal-specific viruses infecting humans. Humans, for example, can be infected with monkeypox on a random basis, causing serious illness in those who are sick. “If such a zoonotic illness gains traction, a severe epidemic might occur due to increased adaptation to its human host and human-to-human transmission,” he warns.
Computers are being used to develop novel medications.
As a result, antiviral medications that inhibit viral gene expression would be very useful. Researchers can now use a rational, structure-based computational method to build inhibitors by understanding the atomic structures of RNA polymerase in various states. Such research, which are fundamentally different from traditional experimental procedures in terms of methodology, are already well underway.
Viruses that Cause Smallpox
People born before 1976, at least in Germany, have a visible scar from their smallpox vaccination on their upper arm. Vaccination was mandatory in Germany at the time. This vaccine is one of the most well-known examples of contemporary infection prevention. The deadly smallpox pathogen was eradicated as a result. This infection, formally known as variola virus, was the cause of recurring smallpox epidemics that afflicted humanity until well into the twentieth century, killing millions of people.
People have known about early types of an inoculation since antiquity, when they inserted the scab of a cured smallpox blister into a minor wound in the hopes of preventing a serious sickness. The treatment known as “variolation” was used in Europe in the 18th century, including at the Juliusspital in Würzburg. In 1976, British physician Edward Jenner made a breakthrough in the fight against smallpox by substituting the innocuous horsepox or cowpox pathogen for the much more dangerous smallpox virus.