Viral Pathogen No More - See Ya Smallpox
Mit Patel and Andrew Pemberton, from the 2020 Hiram College Genetics course, bring us an ancient human scourge that is here no more - the only pathogen wiped from the planet so far. Let us hope that smallpox stays a scourge of our past.
Genomics Revolution
Mit Patel and Andrew Pemberton
Episode 43: Variola Virus (Cause of smallpox)
Script:
Welcome to the Genomic Revolution Podcast! This is Mit Patel and Andrew Pemberton from the 2020 Hiram College Genetics course hosting this episode on an orthopoxvirus known as the Variola virus. This virus causes the disease that many of our parents or grandparents may have gotten when they were younger but rather for us millennials we are vaccinated for it. The variola virus or VARV causes the disease smallpox. However, there are some mysteries as to how it originated. According to Igor Babkin, an author of The Origin of the Variola, the descriptions of smallpox can be seen in ancient literature books from India which were written in 6th or even 15th century BC. Historical evidence shows that smallpox has been seen in many countries including India, china, egypt, and even parts of europe. The variola virus has been proven to be only transmitted between sensitive people but it does not show any signs of affecting an animal. Therefore as a result, the majority of the sensitive people will have two outcomes: be immune or die which will cause the virus to fade. Many researchers have come to conclude that animal domestication, land farming, and large human settlements about 6000 to 10000 years ago truly caused the emergence of smallpox (Babkin, 2015).
Now you listeners may be wondering why I should care about a disease that we already have a vaccination for? But, truly understanding the history and information on how the resolution was found, gives the idea of how important this virus is. When smallpox was around, it was certainly a devastating disease. On average, out of 10 people about 3 of them would die. And due to this, control efforts started to be implemented. One of the first methods was the use of variolation. Variolation, named after the variola virus, was first used in Asia where a small dried smallpox scab was blown into the nose of an individual. This individual would then contract the disease but a milder form. At the end, the individual would be immune to smallpox. Due to this, only about 1%-2% percent died rather than 30%. By 1700, variolation had spread to India, Africa, and the Ottoman empire. Europeans and Americans tended to variolate by puncturing the skin (CDC, 2016).
On the other hand comes the factual information. So the variola virus is a double stranded DNA with a length of approximately 190 kbp, specifically 186,102 base pairs. A 102 kbp is compromised for a central conserved domain, which encodes for multiple different proteins. The virus encodes for about 200 proteins altogether all having different functions. About 80 of those encoded proteins are located in the terminal regions of the genome, where proteins related to host immune invasion are encoded.
The variola virus belongs to the genus of Orthopoxvirus a nd is in the family of Poxvirus (Babkin and Babkina). Research done by Mackett and Archard performed DNA sequencing of several organisms from the genus of Orthopoxvirus (Mackett and Archard). Using restriction endonuclease, they analyzed the genome structure of several viruses and discovered that there is a central conserved region in Orthopoxvirus organisms (Mackett and Archard). It was determined that these highly conserved regions are important to vital function of the virus, including DNA replication and repair, transcription and such (Mackett and Archard). The sequenced DNA also showed variation of the terminus end. This variation is how the Orthopoxvirus viruses vary and is how monkeypox virus infects monkeys and why variola virus is specific to humans (Mackett and Archard). Genome sequencing of the variola virus and closely related virus has revealed which regions of the DNA determine function of the Orthopoxvirus including the variola virus.
Another area where the genome sequence of Variola Virus has been used is to create a phylogenetic tree, or a tree that shows evolutionary relationships among different organisms and in our case viruses. In a paper published by Smithson and other authors, their core group members used one of the first sequenced ancient variola virus genomes. With this, they removed sequencing tags and conducted manual gap-spanning reads. This new assembly was used along with other orthopoxvirus genomes like camelpox and taterapox to determine the last common ancestor of the VARV virus. Their analysis of these different genomes including variola virus lead them to conclude that single nucleotide polymorphisms and amino acid changes in the vaccinia virus ortholog associated to the VARV host specificity and virulence. Furthermore, it was found that these traits were introduced prior to the rise of recent pox viruses. An interesting fact from this paper is that when comparing the ancient and modern VARV genome sequences there is measurable drift in Adenine and thymine richness (Smithson, 2017).
A large worry of many is the reemergence of the smallpox virus. In a paper by Theves and others, they exhumed bodies from an elite burial dating back to 1730s to 1740s, due to the burial time being in the winter and lack of trauma, the authors hypothesized that they died because of a pathogen. At first they thought it might have been a bacterial pathogen, but when they could not find any evidence they searched for a virus (Thèves et al.). After some searching they were able to identify some DNA fragments that were from the poxvirus family, since they were humans, it was smallpox (Thèves et al.). The worry of reemergence prompts researchers to sequence all variations of the variola virus, even ancient variations, in order to have the best possible chance to combat the variola virus if it were to mutate and evolve to infect people again.
We would like to thank you all for listening and we would also like to thank Professor Goodner for allowing us to join Genomics Revolution! We hope that you got a great understanding about the variola virus.
References:
Babkin, Igor, and Irina Babkina. "The Origin Of The Variola Virus". Viruses, vol 7, no.3, 2015, pp. 1100-1112. MDPI AG, doi:10.3390/v7031100. Accessed 9 Apr 2020.
“History of Smallpox.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 30 Aug. 2016, www.cdc.gov/smallpox/history/history.html.
Mackett, M, and L.C. Archard. "Conservation And Variation In Orthopoxvirus Genome Structure". General Virology, vol 45, no. 3, 1979, pp. 683-701., Accessed 4 Apr 2020.
Smithson, Chad et al. “Re-Assembly and Analysis of an Ancient Variola Virus Genome.” Viruses vol. 9,9 253. 8 Sep. 2017, doi:10.3390/v9090253
Thèves, C. et al. "The Rediscovery Of Smallpox". Clinical Microbiology And Infection, vol 20, no. 3, 2014, pp. 210-218. Elsevier BV, doi:10.1111/1469-0691.12536.
Mit Patel and Andrew Pemberton
Episode 43: Variola Virus (Cause of smallpox)
Script:
Welcome to the Genomic Revolution Podcast! This is Mit Patel and Andrew Pemberton from the 2020 Hiram College Genetics course hosting this episode on an orthopoxvirus known as the Variola virus. This virus causes the disease that many of our parents or grandparents may have gotten when they were younger but rather for us millennials we are vaccinated for it. The variola virus or VARV causes the disease smallpox. However, there are some mysteries as to how it originated. According to Igor Babkin, an author of The Origin of the Variola, the descriptions of smallpox can be seen in ancient literature books from India which were written in 6th or even 15th century BC. Historical evidence shows that smallpox has been seen in many countries including India, china, egypt, and even parts of europe. The variola virus has been proven to be only transmitted between sensitive people but it does not show any signs of affecting an animal. Therefore as a result, the majority of the sensitive people will have two outcomes: be immune or die which will cause the virus to fade. Many researchers have come to conclude that animal domestication, land farming, and large human settlements about 6000 to 10000 years ago truly caused the emergence of smallpox (Babkin, 2015).
Now you listeners may be wondering why I should care about a disease that we already have a vaccination for? But, truly understanding the history and information on how the resolution was found, gives the idea of how important this virus is. When smallpox was around, it was certainly a devastating disease. On average, out of 10 people about 3 of them would die. And due to this, control efforts started to be implemented. One of the first methods was the use of variolation. Variolation, named after the variola virus, was first used in Asia where a small dried smallpox scab was blown into the nose of an individual. This individual would then contract the disease but a milder form. At the end, the individual would be immune to smallpox. Due to this, only about 1%-2% percent died rather than 30%. By 1700, variolation had spread to India, Africa, and the Ottoman empire. Europeans and Americans tended to variolate by puncturing the skin (CDC, 2016).
On the other hand comes the factual information. So the variola virus is a double stranded DNA with a length of approximately 190 kbp, specifically 186,102 base pairs. A 102 kbp is compromised for a central conserved domain, which encodes for multiple different proteins. The virus encodes for about 200 proteins altogether all having different functions. About 80 of those encoded proteins are located in the terminal regions of the genome, where proteins related to host immune invasion are encoded.
The variola virus belongs to the genus of Orthopoxvirus a nd is in the family of Poxvirus (Babkin and Babkina). Research done by Mackett and Archard performed DNA sequencing of several organisms from the genus of Orthopoxvirus (Mackett and Archard). Using restriction endonuclease, they analyzed the genome structure of several viruses and discovered that there is a central conserved region in Orthopoxvirus organisms (Mackett and Archard). It was determined that these highly conserved regions are important to vital function of the virus, including DNA replication and repair, transcription and such (Mackett and Archard). The sequenced DNA also showed variation of the terminus end. This variation is how the Orthopoxvirus viruses vary and is how monkeypox virus infects monkeys and why variola virus is specific to humans (Mackett and Archard). Genome sequencing of the variola virus and closely related virus has revealed which regions of the DNA determine function of the Orthopoxvirus including the variola virus.
Another area where the genome sequence of Variola Virus has been used is to create a phylogenetic tree, or a tree that shows evolutionary relationships among different organisms and in our case viruses. In a paper published by Smithson and other authors, their core group members used one of the first sequenced ancient variola virus genomes. With this, they removed sequencing tags and conducted manual gap-spanning reads. This new assembly was used along with other orthopoxvirus genomes like camelpox and taterapox to determine the last common ancestor of the VARV virus. Their analysis of these different genomes including variola virus lead them to conclude that single nucleotide polymorphisms and amino acid changes in the vaccinia virus ortholog associated to the VARV host specificity and virulence. Furthermore, it was found that these traits were introduced prior to the rise of recent pox viruses. An interesting fact from this paper is that when comparing the ancient and modern VARV genome sequences there is measurable drift in Adenine and thymine richness (Smithson, 2017).
A large worry of many is the reemergence of the smallpox virus. In a paper by Theves and others, they exhumed bodies from an elite burial dating back to 1730s to 1740s, due to the burial time being in the winter and lack of trauma, the authors hypothesized that they died because of a pathogen. At first they thought it might have been a bacterial pathogen, but when they could not find any evidence they searched for a virus (Thèves et al.). After some searching they were able to identify some DNA fragments that were from the poxvirus family, since they were humans, it was smallpox (Thèves et al.). The worry of reemergence prompts researchers to sequence all variations of the variola virus, even ancient variations, in order to have the best possible chance to combat the variola virus if it were to mutate and evolve to infect people again.
We would like to thank you all for listening and we would also like to thank Professor Goodner for allowing us to join Genomics Revolution! We hope that you got a great understanding about the variola virus.
References:
Babkin, Igor, and Irina Babkina. "The Origin Of The Variola Virus". Viruses, vol 7, no.3, 2015, pp. 1100-1112. MDPI AG, doi:10.3390/v7031100. Accessed 9 Apr 2020.
“History of Smallpox.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 30 Aug. 2016, www.cdc.gov/smallpox/history/history.html.
Mackett, M, and L.C. Archard. "Conservation And Variation In Orthopoxvirus Genome Structure". General Virology, vol 45, no. 3, 1979, pp. 683-701., Accessed 4 Apr 2020.
Smithson, Chad et al. “Re-Assembly and Analysis of an Ancient Variola Virus Genome.” Viruses vol. 9,9 253. 8 Sep. 2017, doi:10.3390/v9090253
Thèves, C. et al. "The Rediscovery Of Smallpox". Clinical Microbiology And Infection, vol 20, no. 3, 2014, pp. 210-218. Elsevier BV, doi:10.1111/1469-0691.12536.